Econstudentlog

Random stuff

I have almost stopped posting posts like these, which has resulted in the accumulation of a very large number of links and studies which I figured I might like to blog at some point. This post is mainly an attempt to deal with the backlog – I won’t cover the material in too much detail.

i. Do Bullies Have More Sex? The answer seems to be a qualified yes. A few quotes:

“Sexual behavior during adolescence is fairly widespread in Western cultures (Zimmer-Gembeck and Helfland 2008) with nearly two thirds of youth having had sexual intercourse by the age of 19 (Finer and Philbin 2013). […] Bullying behavior may aid in intrasexual competition and intersexual selection as a strategy when competing for mates. In line with this contention, bullying has been linked to having a higher number of dating and sexual partners (Dane et al. 2017; Volk et al. 2015). This may be one reason why adolescence coincides with a peak in antisocial or aggressive behaviors, such as bullying (Volk et al. 2006). However, not all adolescents benefit from bullying. Instead, bullying may only benefit adolescents with certain personality traits who are willing and able to leverage bullying as a strategy for engaging in sexual behavior with opposite-sex peers. Therefore, we used two independent cross-sectional samples of older and younger adolescents to determine which personality traits, if any, are associated with leveraging bullying into opportunities for sexual behavior.”

“…bullying by males signal the ability to provide good genes, material resources, and protect offspring (Buss and Shackelford 1997; Volk et al. 2012) because bullying others is a way of displaying attractive qualities such as strength and dominance (Gallup et al. 2007; Reijntjes et al. 2013). As a result, this makes bullies attractive sexual partners to opposite-sex peers while simultaneously suppressing the sexual success of same-sex rivals (Gallup et al. 2011; Koh and Wong 2015; Zimmer-Gembeck et al. 2001). Females may denigrate other females, targeting their appearance and sexual promiscuity (Leenaars et al. 2008; Vaillancourt 2013), which are two qualities relating to male mate preferences. Consequently, derogating these qualities lowers a rivals’ appeal as a mate and also intimidates or coerces rivals into withdrawing from intrasexual competition (Campbell 2013; Dane et al. 2017; Fisher and Cox 2009; Vaillancourt 2013). Thus, males may use direct forms of bullying (e.g., physical, verbal) to facilitate intersexual selection (i.e., appear attractive to females), while females may use relational bullying to facilitate intrasexual competition, by making rivals appear less attractive to males.”

The study relies on the use of self-report data, which I find very problematic – so I won’t go into the results here. I’m not quite clear on how those studies mentioned in the discussion ‘have found self-report data [to be] valid under conditions of confidentiality’ – and I remain skeptical. You’ll usually want data from independent observers (e.g. teacher or peer observations) when analyzing these kinds of things. Note in the context of the self-report data problem that if there’s a strong stigma associated with being bullied (there often is, or bullying wouldn’t work as well), asking people if they have been bullied is not much better than asking people if they’re bullying others.

ii. Some topical advice that some people might soon regret not having followed, from the wonderful Things I Learn From My Patients thread:

“If you are a teenage boy experimenting with fireworks, do not empty the gunpowder from a dozen fireworks and try to mix it in your mother’s blender. But if you do decide to do that, don’t hold the lid down with your other hand and stand right over it. This will result in the traumatic amputation of several fingers, burned and skinned forearms, glass shrapnel in your face, and a couple of badly scratched corneas as a start. You will spend months in rehab and never be able to use your left hand again.”

iii. I haven’t talked about the AlphaZero-Stockfish match, but I was of course aware of it and did read a bit about that stuff. Here’s a reddit thread where one of the Stockfish programmers answers questions about the match. A few quotes:

“Which of the two is stronger under ideal conditions is, to me, neither particularly interesting (they are so different that it’s kind of like comparing the maximum speeds of a fish and a bird) nor particularly important (since there is only one of them that you and I can download and run anyway). What is super interesting is that we have two such radically different ways to create a computer chess playing entity with superhuman abilities. […] I don’t think there is anything to learn from AlphaZero that is applicable to Stockfish. They are just too different, you can’t transfer ideas from one to the other.”

“Based on the 100 games played, AlphaZero seems to be about 100 Elo points stronger under the conditions they used. The current development version of Stockfish is something like 40 Elo points stronger than the version used in Google’s experiment. There is a version of Stockfish translated to hand-written x86-64 assembly language that’s about 15 Elo points stronger still. This adds up to roughly half the Elo difference between AlphaZero and Stockfish shown in Google’s experiment.”

“It seems that Stockfish was playing with only 1 GB for transposition tables (the area of memory used to store data about the positions previously encountered in the search), which is way too little when running with 64 threads.” [I seem to recall a comp sci guy observing elsewhere that this was less than what was available to his smartphone version of Stockfish, but I didn’t bookmark that comment].

“The time control was a very artificial fixed 1 minute/move. That’s not how chess is traditionally played. Quite a lot of effort has gone into Stockfish’s time management. It’s pretty good at deciding when to move quickly, and when to spend a lot of time on a critical decision. In a fixed time per move game, it will often happen that the engine discovers that there is a problem with the move it wants to play just before the time is out. In a regular time control, it would then spend extra time analysing all alternative moves and trying to find a better one. When you force it to move after exactly one minute, it will play the move it already know is bad. There is no doubt that this will cause it to lose many games it would otherwise have drawn.”

iv. Thrombolytics for Acute Ischemic Stroke – no benefit found.

“Thrombolysis has been rigorously studied in >60,000 patients for acute thrombotic myocardial infarction, and is proven to reduce mortality. It is theorized that thrombolysis may similarly benefit ischemic stroke patients, though a much smaller number (8120) has been studied in relevant, large scale, high quality trials thus far. […] There are 12 such trials 1-12. Despite the temptation to pool these data the studies are clinically heterogeneous. […] Data from multiple trials must be clinically and statistically homogenous to be validly pooled.14 Large thrombolytic studies demonstrate wide variations in anatomic stroke regions, small- versus large-vessel occlusion, clinical severity, age, vital sign parameters, stroke scale scores, and times of administration. […] Examining each study individually is therefore, in our opinion, both more valid and more instructive. […] Two of twelve studies suggest a benefit […] In comparison, twice as many studies showed harm and these were stopped early. This early stoppage means that the number of subjects in studies demonstrating harm would have included over 2400 subjects based on originally intended enrollments. Pooled analyses are therefore missing these phantom data, which would have further eroded any aggregate benefits. In their absence, any pooled analysis is biased toward benefit. Despite this, there remain five times as many trials showing harm or no benefit (n=10) as those concluding benefit (n=2), and 6675 subjects in trials demonstrating no benefit compared to 1445 subjects in trials concluding benefit.”

“Thrombolytics for ischemic stroke may be harmful or beneficial. The answer remains elusive. We struggled therefore, debating between a ‘yellow’ or ‘red’ light for our recommendation. However, over 60,000 subjects in trials of thrombolytics for coronary thrombosis suggest a consistent beneficial effect across groups and subgroups, with no studies suggesting harm. This consistency was found despite a very small mortality benefit (2.5%), and a very narrow therapeutic window (1% major bleeding). In comparison, the variation in trial results of thrombolytics for stroke and the daunting but consistent adverse effect rate caused by ICH suggested to us that thrombolytics are dangerous unless further study exonerates their use.”

“There is a Cochrane review that pooled estimates of effect. 17 We do not endorse this choice because of clinical heterogeneity. However, we present the NNT’s from the pooled analysis for the reader’s benefit. The Cochrane review suggested a 6% reduction in disability […] with thrombolytics. This would mean that 17 were treated for every 1 avoiding an unfavorable outcome. The review also noted a 1% increase in mortality (1 in 100 patients die because of thrombolytics) and a 5% increase in nonfatal intracranial hemorrhage (1 in 20), for a total of 6% harmed (1 in 17 suffers death or brain hemorrhage).”

v. Suicide attempts in Asperger Syndrome. An interesting finding: “Over 35% of individuals with AS reported that they had attempted suicide in the past.”

Related: Suicidal ideation and suicide plans or attempts in adults with Asperger’s syndrome attending a specialist diagnostic clinic: a clinical cohort study.

“374 adults (256 men and 118 women) were diagnosed with Asperger’s syndrome in the study period. 243 (66%) of 367 respondents self-reported suicidal ideation, 127 (35%) of 365 respondents self-reported plans or attempts at suicide, and 116 (31%) of 368 respondents self-reported depression. Adults with Asperger’s syndrome were significantly more likely to report lifetime experience of suicidal ideation than were individuals from a general UK population sample (odds ratio 9·6 [95% CI 7·6–11·9], p<0·0001), people with one, two, or more medical illnesses (p<0·0001), or people with psychotic illness (p=0·019). […] Lifetime experience of depression (p=0·787), suicidal ideation (p=0·164), and suicide plans or attempts (p=0·06) did not differ significantly between men and women […] Individuals who reported suicide plans or attempts had significantly higher Autism Spectrum Quotient scores than those who did not […] Empathy Quotient scores and ages did not differ between individuals who did or did not report suicide plans or attempts (table 4). Patients with self-reported depression or suicidal ideation did not have significantly higher Autism Spectrum Quotient scores, Empathy Quotient scores, or age than did those without depression or suicidal ideation”.

The fact that people with Asperger’s are more likely to be depressed and contemplate suicide is consistent with previous observations that they’re also more likely to die from suicide – for example a paper I blogged a while back found that in that particular (large Swedish population-based cohort-) study, people with ASD were more than 7 times as likely to die from suicide than were the comparable controls.

Also related: Suicidal tendencies hard to spot in some people with autism.

This link has some great graphs and tables of suicide data from the US.

Also autism-related: Increased perception of loudness in autism. This is one of the ‘important ones’ for me personally – I am much more sound-sensitive than are most people.

vi. Early versus Delayed Invasive Intervention in Acute Coronary Syndromes.

“Earlier trials have shown that a routine invasive strategy improves outcomes in patients with acute coronary syndromes without ST-segment elevation. However, the optimal timing of such intervention remains uncertain. […] We randomly assigned 3031 patients with acute coronary syndromes to undergo either routine early intervention (coronary angiography ≤24 hours after randomization) or delayed intervention (coronary angiography ≥36 hours after randomization). The primary outcome was a composite of death, myocardial infarction, or stroke at 6 months. A prespecified secondary outcome was death, myocardial infarction, or refractory ischemia at 6 months. […] Early intervention did not differ greatly from delayed intervention in preventing the primary outcome, but it did reduce the rate of the composite secondary outcome of death, myocardial infarction, or refractory ischemia and was superior to delayed intervention in high-risk patients.”

vii. Some wikipedia links:

Behrens–Fisher problem.
Sailing ship tactics (I figured I had to read up on this if I were to get anything out of the Aubrey-Maturin books).
Anatomical terms of muscle.
Phatic expression (“a phatic expression […] is communication which serves a social function such as small talk and social pleasantries that don’t seek or offer any information of value.”)
Three-domain system.
Beringian wolf (featured).
Subdural hygroma.
Cayley graph.
Schur polynomial.
Solar neutrino problem.
Hadamard product (matrices).
True polar wander.
Newton’s cradle.

viii. Determinant versus permanent (mathematics – technical).

ix. Some years ago I wrote a few English-language posts about some of the various statistical/demographic properties of immigrants living in Denmark, based on numbers included in a publication by Statistics Denmark. I did it by translating the observations included in that publication, which was only published in Danish. I was briefly considering doing the same thing again when the 2017 data arrived, but I decided not to do it as I recalled that it took a lot of time to write those posts back then, and it didn’t seem to me to be worth the effort – but Danish readers might be interested to have a look at the data, if they haven’t already – here’s a link to the publication Indvandrere i Danmark 2017.

x. A banter blitz session with grandmaster Peter Svidler, who recently became the first Russian ever to win the Russian Chess Championship 8 times. He’s currently shared-second in the World Rapid Championship after 10 rounds and is now in the top 10 on the live rating list in both classical and rapid – seems like he’s had a very decent year.

xi. I recently discovered Dr. Whitecoat’s blog. The patient encounters are often interesting.

December 28, 2017 Posted by | Astronomy, autism, Biology, Cardiology, Chess, Computer science, History, Mathematics, Medicine, Neurology, Physics, Psychiatry, Psychology, Random stuff, Statistics, Studies, Wikipedia, Zoology | Leave a comment

A few SSC comments

I recently left a few comments in an open thread on SSC, and I figured it might make sense to crosspost some of the comments made there here on the blog. I haven’t posted all my contributions to the debate here, rather I’ve just quoted some specific comments and observations which might be of interest. I’ve also added some additional remarks and comments which relate to the topics discussed. Here’s the main link (scroll down to get to my comments).

“One thing worth keeping in mind when evaluating pre-modern medicine characterizations of diabetes and the natural history of diabetes is incidentally that especially to the extent that one is interested in type 1 survivorship bias is a major problem lurking in the background. Prognostic estimates of untreated type 1 based on historical accounts of how long people could live with the disease before insulin are not in my opinion likely to be all that reliable, because the type of patients that would be recognized as (type 1) diabetics back then would tend to mainly be people who had the milder forms, because they were the only ones who lived long enough to reach a ‘doctor’; and the longer they lived, and the milder the sub-type, the more likely they were to be studied/’diagnosed’. I was a 2-year old boy who got unwell on a Tueday and was hospitalized three days later. Avicenna would have been unlikely to have encountered me, I’d have died before he saw me. (Similar lines of reasoning might lead to an argument that the incidence of diseases like type 1 diabetes may also today be underdiagnosed in developing countries with poorly developed health care systems.)”

Douglas Knight mentioned during our exchange that medical men of the far past might have been more likely to attend to patients with acute illnesses than patients with chronic conditions, making them more likely to attend to such cases than would otherwise be the case, a point I didn’t discuss in any detail during the exchange. I did however think it important to note here that information exchange was significantly slower, and transportation costs were much higher, in the past than they are today. This should make such a bias less relevant, all else equal. Avicenna and his colleagues couldn’t take a taxi, or learn by phone that X is sick. He might have preferentially attended to the acute cases he learned about, but given high transportation costs and inefficient communication channels he might often never arrive in time, or at all. A particular problem here is that there are no good data on the unobserved cases, because the only cases we know about today are the ones people like him have told us about.

Some more comments:

“One thing I was considering adding to my remarks about survivorship bias is that it is not in my opinion unlikely that what you might term the nature of the disease has changed over the centuries; indeed it might still be changing today. Globally the incidence of type 1 has been increasing for decades and nobody seems to know why, though there’s consensus about an environmental trigger playing a major role. Maybe incidence is not the only thing that’s changed, maybe e.g. the time course of the ‘average case’ has also changed? Maybe due to secondary factors; better nutritional status now equals slower progression of beta cell failure than was the case in the past? Or perhaps the other way around: Less exposure to bacterial agents the immune system throughout evolutionary time has been used to having to deal with today means that the autoimmune process is accelerated today, compared to in the far past where standards of hygiene were different. Who knows? […] Maybe survivorship bias wasn’t that big of a deal, but I think one should be very cautious about which assumptions one might implicitly be making along the way when addressing questions of this sort of nature. Some relevant questions will definitely be unknowable due to lack of good data which we will never be able to obtain.”

I should perhaps interpose here that even if survivorship bias ‘wasn’t that big of a deal’, it’s still sort of a big problem in the analytical setting because it seems perfectly plausible to me to be making the assumption that it might even so have been a big deal. These kinds of problems magnify our error bars and reduce confidence in our conclusions, regardless of the extent to which they actually played a role. When you know the exact sign and magnitude of a given moderating effect you can try to correct for it, but this is very difficult to do when a large range of moderator effect sizes might be considered plausible. It might also here be worth mentioning explicitly that biases such as the survivorship bias mentioned can of course impact a lot of things besides just the prognostic estimates; for example if a lot of cases never come to the attention of the medical people because these people were unavailable (due to distance, cost, lack of information, etc.) to the people who were sick, incidence and prevalence will also implicitly be underestimated. And so on. Back to the comments:

“Once you had me thinking that it might have been harder [for people in the past] to distinguish [between type 1 and type 2 diabetes] than […] it is today, I started wondering about this, and the comments below relate to this topic. An idea that came to mind in relation to the type 1/type 2 distinction and the ability of people in the past to make this distinction: I’ve worked on various identification problems present in the diabetes context before, and I know that people even today make misdiagnoses and e.g. categorize type 1 diabetics as type 2. I asked a diabetes nurse working in the local endocrinology unit about this at one point, and she told me they had actually had a patient not long before then who had been admitted a short while after having been diagnosed with type 2. Turned out he was type 1, so the treatment failed. Misdiagnoses happen for multiple reasons, one is that obese people also sometimes develop type 1, and if it’s an acute onset setting the weight loss is not likely to be very significant. Patient history should in such a case provide the doctor with the necessary clues, but if the guy making the diagnosis is a stressed out GP who’s currently treating a lot of obese patients for type 2, mistakes happen. ‘Pre-scientific method’ this sort of individual would have been inconvenient to encounter, because a ‘counter-example’ like that supposedly demonstrating that the obese/thin(/young/old, acute/protracted…) distinction was ‘invalid’ might have held a lot more weight than it hopefully would today in the age of statistical analysis. A similar problem would be some of the end-stage individuals: A type 1 pre-insulin would be unlikely to live long enough to develop long term complications of the disease, but would instead die of DKA. The problem is that some untreated type 2 patients also die of DKA, though the degree of ketosis varies in type 2 patients. DKA in type 2 could e.g. be triggered by a superimposed cardiovascular event or an infection, increasing metabolic demands to an extent that can no longer be met by the organism, and so might well present just as acutely as it would in a classic acute-onset type 1 case. Assume the opposite bias you mention is playing a role; the ‘doctor’ in the past is more likely to see the patients in such a life-threatening setting than in the earlier stages. He observes a 55 year old fat guy dying in a very similar manner to the way a 12 year old girl died a few months back – very characteristic symptoms, breath smells fruity, Kussmaul respiration, polyuria and polydipsia…). What does he conclude? Are these different diseases?”

Making the doctor’s decision problem even harder is of course the fact that type 2 diabetes even today often goes undiagnosed until complications arise. Some type 2 patients get their diagnosis only after they had their first heart attack as a result of their illness. So the hypothetical obese middle-aged guy presenting with DKA might not have been known by anyone to be ‘a potentially different kind of diabetic’.

‘The Nybbler’ asked this question in the thread: “Wouldn’t reduced selection pressure be a major reason for increase of Type I diabetes? Used to be if you had it, chance of surviving to reproduce was close to nil.”

I’ll mention here that I’ve encountered this kind of theorizing before, but that I’ve never really addressed it – especially the second part – explicitly, though I’ve sometimes felt like doing that. I figured this post might be a decent place to at least scratch the surface. The idea that there are more type 1 diabetics now than there used to be because type 1 diabetics used to die of their disease and now they don’t (…and so now they are able to transmit their faulty genes to subsequent generations, leading to more diabetic individuals over time) sounds sort of reasonable if you don’t know very much about diabetes, but it sounds less reasonable to people who do. Genes matter, and changed selection pressures have probably played a role, but I find it hard to believe this particular mechanism is a major factor. I have included both my of my replies to ‘Nybbler’ below:

First comment:

“I’m not a geneticist and this is sort-of-kind-of near the boundary area of where I feel comfortable providing answers (given that others may be more qualified to evaluate questions like this than I am). However a few observations which might be relevant are the following:

i) Although I’ll later go on to say that vertical transmission is low, I first have to point out that some people who developed type 1 diabetes in the past did in fact have offspring, though there’s no doubt about the condition being fitness-reducing to a very large degree. The median age of diagnosis of type 1 is somewhere in the teenage years (…today. Was it the same way 1000 years ago, or has the age profile changed over time? This again relates to questions asked elsewhere in this discussion…), but people above the age of 30 get type 1 too.

ii) Although type 1 display some level of familia[l] clustering, most cases of type 1 are not the result of diabetics having had children who then proceed to inherit their parents’ disease. To the extent that reduced selection is a driver of increased incidence, the main cause would be broad selection effects pertaining to immune system functioning in general in the total population at risk (i.e. children in general, including many children with what might be termed suboptimal immune system functioning, being more likely to survive and later develop type 1 diabetes), not effects derived from vertical transmission of the disease (from parent to child). Roughly 90% of newly diagnosed type 1 diabetics in population studies have a negative family history of the disease, and on average only 2% of the children of type 1 diabetic mothers, and 5% of the children of type 1 diabetic fathers, go on to develop type 1 diabetes themselves.

iii) Historically vertical transmission has even in modern times been low. On top of the quite low transmission rates mentioned above, until well into the 80es or 90es many type 1 diabetic females were explicitly advised by their medical care providers not to have children, not because of the genetic risk of disease transmission but because pregnancy outcomes were likely to be poor; and many of those who disregarded the advice gave birth to offspring who were at a severe fitness disadvantage from the start. Poorly controlled diabetes during pregnancy leads to a very high risk of birth defects and/or miscarriage, and may pose health risks to the mother as well through e.g. an increased risk of preeclampsia (relevant link). It is only very recently that we’ve developed the knowledge and medical technology required to make pregnancy a reasonably safe option for female diabetics. You still had some diabetic females who gave birth before developing diabetes, like in the far past, and the situation was different for males, but either way I feel reasonably confident claiming that if you look for genetic causes of increasing incidence, vertical transmission should not be the main factor to consider.

iv) You need to be careful when evaluating questions like these to keep a distinction between questions relating to drivers of incidence and questions relating to drivers of prevalence at the back of your mind. These two sets of questions are not equivalent.

v) If people are interested to know more about the potential causes of increased incidence of type 1 diabetes, here’s a relevant review paper.”

I followed up with a second comment a while later, because I figured a few points of interest might not have been sufficiently well addressed in my first comment:

“@Nybbler:

A few additional remarks.

i) “Temporal trends in chronic disease incidence rates are almost certainly environmentally induced. If one observes a 50% increase in the incidence of a disorder over 20 yr, it is most likely the result of changes in the environment because the gene pool cannot change that rapidly. Type 1 diabetes is a very dynamic disease. […] results clearly demonstrate that the incidence of type 1 diabetes is rising, bringing with it a large public health problem. Moreover, these findings indicate that something in our environment is changing to trigger a disease response. […] With the exception of a possible role for viruses and infant nutrition, the specific environmental determinants that initiate or precipitate the onset of type 1 diabetes remain unclear.” (Type 1 Diabetes, Etiology and Treatment. Just to make it perfectly clear that although genes matter, environmental factors are the most likely causes of the rising levels of incidence we’ve seen in recent times.)

ii. Just as you need to always keep incidence and prevalence in mind when analyzing these things (for example low prevalence does not mean incidence is necessarily low, or was low in the past; low prevalence could also be a result of a combination of high incidence and high case mortality. I know from experience that even diabetes researchers tend to sometimes overlook stuff like this), you also need to keep the distinction between genotype and phenotype in mind. Given the increased importance of one or more environmental triggers in modern times, penetrance is likely to have changed over time. This means for example that ‘a diabetic genotype’ may have been less fitness reducing in the past than it is today, even if the associated ‘diabetic phenotype’ may on the other hand have been much more fitness reducing than it is now; people who developed diabetes died, but many of the people who might in the current environment be considered high-risk cases may not have been high risk in the far past, because the environmental trigger causing disease was absent, or rarely encountered. Assessing genetic risk for diabetes is complicated, and there’s no general formula for calculating this risk either in the type 1 or type 2 case; monogenic forms of diabetes do exist, but they account for a very small proportion of cases (1-5% of diabetes in young individuals) – most cases are polygenic and display variable levels of penetrance. Note incidentally that a story of environmental factors becoming more important over time is actually implicitly also, to the extent that diabetes is/has been fitness-reducing, a story of selection pressures against diabetic genotypes potentially increasing over time, rather than the opposite (which seems to be the default assumption when only taking into account stuff like the increased survival rates of type 1 diabetics over time). This stuff is complicated.”

I wasn’t completely happy with my second comment (I wrote it relatively fast and didn’t have time to go over it in detail after I’d written it), so I figured it might make sense to add a few details here. One key idea here is of course that you need to distinguish between people who are ‘vulnerable’ to developing type 1 diabetes, and people who actually do develop the disease. If fewer people who today would be considered ‘vulnerable’ developed the disease in the past than is the case now, selection against the ‘vulnerable’ genotype would – all else equal – have been lower throughout evolutionary time than it is today.

All else is not equal because of insulin treatment. But a second key point is that when you’re interested in fitness effects, mortality is not the only variable of interest; many diabetic women who were alive because of insulin during the 20th century but who were also being discouraged from having children may well have left no offspring. Males who committed suicide or died from kidney failure in their twenties likely also didn’t leave many offspring. Another point related to the mortality variable is that although diabetes mortality might in the past have been approximated reasonably well by a simple binary outcome variable/process (no diabetes = alive, diabetes = dead), type 1 diabetes has had large effects on mortality rates also throughout the chunk of history during which insulin has been a treatment option; mortality rates 3 or 4 times higher than those of non-diabetics are common in population studies, and such mortality rates add up over time even if base rates are low, especially in a fitness context, as they for most type 1 diabetics are at play throughout the entire fertile period of the life history. Type 2 diabetes is diagnosed mainly in middle-aged individuals, many of whom have already completed their reproductive cycle, but type 1 diabetes is very different in that respect. Of course there are multiple indirect effects at play as well here, e.g. those of mate choice; which is the more attractive potential partner, the individual with diabetes or the one without? What if the diabetic also happens to be blind?

A few other quotes from the comments:

“The majority of patients on insulin in the US are type 2 diabetics, and it is simply wrong that type 2 diabetics are not responsive to insulin treatment. They were likely found to be unresponsive in early trials because of errors of dosage, as they require higher levels of the drug to obtain the same effect as will young patients diagnosed with type 1 (the primary group on insulin in the 30es). However, insulin treatment is not the first-line option in the type 2 context because the condition can usually be treated with insulin-sensitizing agents for a while, until they fail (those drugs will on average fail in something like ~50% of subjects within five years of diagnosis, which is the reason – combined with the much (order(/s, depending on where you are) of magnitude) higher prevalence of type 2 – why a majority of patients on insulin have type 2), and these tend to a) be more acceptable to the patients (a pill vs an injection) and b) have fewer/less severe side effects on average. One reason which also played a major role in delaying the necessary use of insulin to treat type 2 diabetes which could not be adequately controlled via other means was incidentally the fact that insulin ca[u]ses weight gain, and the obesity-type 2 link was well known.”

“Type 1 is autoimmune, and most cases of type 2 are not, but some forms of type 2 seem to have an autoimmune component as well (“the overall autoantibody frequency in type 2 patients varies between 6% and 10%” – source) (these patients, who can be identified through genetic markers, will on average proceed to insulin dependence because of treatment failure in the context of insulin sensitizing-agents much sooner than is usually the case in patients with type 2). In general type 1 is caused by autoimmune beta cell destruction and type 2 mainly by insulin resistance, but combinations of the two are also possible […], and patients with type 1 can develop insulin resistance just as patients with type 2 can lose beta cells via multiple pathways. The major point here being that the sharp diagnostic distinction between type 1 and type 2 is a major simplification of what’s really going on, and it’s hiding a lot of heterogeneity in both samples. Some patients with type 1 will develop diabetes acutely or subacutely, within days or hours, whereas others will have elevated blood glucose levels for months before medical attention is received and a diagnosis is made (you can tell whether or not blood glucose has been elevated pre-diagnosis by looking at one of the key diagnostic variables, Hba1c, which is a measure of the average blood glucose over the entire lifetime of a red blood cell (~3-4 months) – in some newly diagnosed type 1s, this variable is elevated, in others it is not. Some type 1 patients will develop other autoimmune conditions later on, whereas others will not, and some will be more likely to develop complications than others who have the same level of glycemic control.

Type 1 and type 2 diabetes are quite different conditions, but in terms of many aspects of the diseases there are significant degrees of overlap (for example they develop many of the same complications, for similar (pathophysiological) reasons), yet they are both called diabetes. You don’t want to treat a type 2 diabetic with insulin if he can be treated with metformin, and treating a type 1 with metformin will not help – so different treatments are required.”

“In terms of whether it’s ideal to have one autistic diagnostic group or two (…or three, or…) [this question was a starting point for the debate from which I quote, but I decided not to go much into this topic here], I maintain that to a significant extent the answer to that question relates to what the diagnosis is supposed to accomplish. If it makes sense for researchers to be able to distinguish, which it probably does, but it is not necessary for support organizers/providers to know the subtype in order to provide aid, then you might end up with one ‘official’ category and two (or more) ‘research categories’. I would be fine with that (but again I don’t find this discussion interesting). Again a parallel might be made to diabetes research: Endocrinologists are well aware that there’s a huge amount of variation in both the type 1 and type 2 samples, to the extent that it’s sort of silly to even categorize these illnesses using the same name, but they do it anyway for reasons which are sort of obvious. If you’re type 1 diabetic and you have an HLA mutation which made you vulnerable to diabetes and you developed diabetes at the age of 5, well, we’ll start you on insulin, try to help you achieve good metabolic control, and screen you regularly for complications. If on the other hand you’re an adult guy who due to a very different genetic vulnerability developed type 1 diabetes at the age of 30 (and later on Graves’ disease at the age of 40, due to the same mutation), well, we’ll start you on insulin, try to help you achieve good metabolic control, and screen you regularly for complications. The only thing type 1 diabetics have in common is the fact that their beta cells die due to some autoimmune processes. But it could easily be conceived of instead as literally hundreds of different diseases. Currently the distinctions between the different disease-relevant pathophysiological processes don’t matter very much in the treatment context, but they might do that at some point in the future, and if that happens the differences will start to become more important. People might at that point start to talk about type 1a diabetes, which might be the sort you can delay or stop with gene therapy, and type 1b which you can’t delay or stop (…yet). Lumping ‘different’ groups together into one diagnostic category is bad if it makes you overlook variation which is important, and this may be a problem in the autism context today, but regardless of the sizes of the diagnostic groups you’ll usually still end up with lots of residual (‘unexplained’) variation.”

I can’t recall to which extent I’ve discussed this last topic – the extent to which type 1 diabetes is best modeled as one illness or many – but it’s an important topic to keep at the back of your mind when you’re reading the diabetes literature. I’m assuming that in some contexts the subgroup heterogeneities, e.g. in terms of treatment response, will be much more important than in other contexts, so you probably need specific subject matter knowledge to make any sort of informed decision about to which extent potential unobserved heterogeneities may be important in a specific setting, but even if you don’t have that ‘a healthy skepticism’, derived from keeping the potential for these factors to play a role in mind, is likely to be more useful than the alternative. In that context I think the (poor, but understandable) standard practice of lumping together type 1 and type 2 diabetics in studies may lead many people familiar with the differences between the two conditions to think along the lines that as long as you know the type, you’re good to go – ‘at least this study only looked at type 1 individuals, not like those crappy studies which do not distinguish between type 1 and type 2, so I can definitely trust these results to apply to the subgroup of type 1 diabetics in which I’m interested’ – and I think this tendency, to the extent that it exists, is unfortunate.

July 8, 2017 Posted by | autism, Diabetes, Epidemiology, Genetics, Medicine, Psychology | Leave a comment

A few autism papers

i. The anterior insula in autism: Under-connected and under-examined.

“While the past decade has witnessed a proliferation of neuroimaging studies of autism, theoretical approaches for understanding systems-level brain abnormalities remain poorly developed. We propose a novel anterior insula-based systems-level model for investigating the neural basis of autism, synthesizing recent advances in brain network functional connectivity with converging evidence from neuroimaging studies in autism. The anterior insula is involved in interoceptive, affective and empathic processes, and emerging evidence suggests it is part of a “salience network” integrating external sensory stimuli with internal states. Network analysis indicates that the anterior insula is uniquely positioned as a hub mediating interactions between large-scale networks involved in externally- and internally-oriented cognitive processing. A recent meta-analysis identifies the anterior insula as a consistent locus of hypoactivity in autism. We suggest that dysfunctional anterior insula connectivity plays an important role in autism. […]

Increasing evidence for abnormal brain connectivity in autism comes from studies using functional connectivity measures […] These findings support the hypothesis that under-connectivity between specific brain regions is a characteristic feature of ASD. To date, however, few studies have examined functional connectivity within and between key large-scale canonical brain networks in autism […] The majority of published studies to date have examined connectivity of specific individual brain regions, without a broader theoretically driven systems-level approach.

We propose that a systems-level approach is critical for understanding the neurobiology of autism, and that the anterior insula is a key node in coordinating brain network interactions, due to its unique anatomy, location, function, and connectivity.”

ii. Romantic Relationships and Relationship Satisfaction Among Adults With Asperger Syndrome and High‐Functioning Autism.

“Participants, 31 recruited via an outpatient clinic and 198 via an online survey, were asked to answer a number of self-report questionnaires. The total sample comprised 229 high-functioning adults with ASD (40% males, average age: 35 years). […] Of the total sample, 73% indicated romantic relationship experience and only 7% had no desire to be in a romantic relationship. ASD individuals whose partner was also on the autism spectrum were significantly more satisfied with their relationship than those with neurotypical partners. Severity of autism, schizoid symptoms, empathy skills, and need for social support were not correlated with relationship status. […] Our findings indicate that the vast majority of high-functioning adults with ASD are interested in romantic relationships.”

Those results are very different from other results in the field – for example: “[a] meta-analysis of follow-up studies examining outcomes of ASD individuals revealed that, [o]n average only 14% of the individuals included in the reviewed studies were married or ha[d] a long-term, intimate relationship (Howlin, 2012)” – and one major reason is that they only include high-functioning autistics. I feel sort of iffy about the validity of the selection method used for procuring the online sample, this may also be a major factor (almost one third of them had a university degree so this is definitely not a random sample of high-functioning autistics; ‘high-functioning’ autistics are not that high-functioning in the general setting. Also, the sex ratio is very skewed as 60% of the participants in the study were female. A sex ratio like that may not sound like a big problem, but it is a major problem because a substantial majority of individuals with mild autism are males. Whereas the sex ratio is almost equal in the context of syndromic ASD, non-syndromic ASD is much more prevalent in males, with sex ratios approaching 1:7 in milder cases (link). These people are definitely looking at the milder cases, which means that a sample which skews female will not be remotely similar to most random samples of such individuals taken in the community setting. And this matters because females do better than males. A discussion can be had about to which extent women are under-diagnosed, but I have not seen data convincing me this is a major problem. It’s important to keep in mind in that context that the autism diagnosis is not based on phenotype alone, but on a phenotype-environment interaction; if you have what might be termed ‘an autistic phenotype’ but you are not suffering any significant ill effects as a result of this because you’re able to compensate relatively well (i.e. you are able to handle ‘the environment’ reasonably well despite the neurological makeup you’ve ended up with), you should not get an autism diagnosis – a diagnostic requirement is ‘clinically significant impairment in functioning’.

Anyway some more related data from the publication:

“Studies that analyze outcomes exclusively for ASD adults without intellectual impairment are rare. […] Engström, Ekström, and Emilsson (2003) recruited previous patients with an ASD diagnosis from four psychiatric clinics in Sweden. They reported that 5 (31%) of 16 adults with ASD had ”some form of relation with a partner.” Hofvander et al. (2009) analyzed data from 122 participants who had been referred to outpatient clinics for autism diagnosis. They found that 19 (16%) of all participants had lived in a long-term relationship.
Renty and Roeyers (2006) […] reported that at the time of the[ir] study 19% of 58 ASD adults had a romantic relationship and 8.6% were married or living with a partner. Cederlund, Hagberg, Billstedt, Gillberg, and Gillberg (2008) conducted a follow-up study of male individuals (aged 16–36 years) who had been diagnosed with Asperger syndrome at least 5 years before. […] at the time of the study, three (4%) [out of 76 male ASD individuals] of them were living in a long-term romantic relationship and 10 (13%) had had romantic relationships in the past.”

A few more data and observations from the study:

“A total of 166 (73%) of the 229 participants endorsed currently being in a romantic relationship or having a history of being in a relationship; 100 (44%) reported current involvement in a romantic relationship; 66 (29%) endorsed that they were currently single but have a history of involvement in a romantic relationship; and 63 (27%) participants did not have any experience with romantic relationships. […] Participants without any romantic relationship experience were significantly more likely to be male […] According to participants’ self-report, one fifth (20%) of the 100 participants who were currently involved in a romantic relationship were with an ASD partner. […] Of the participants who were currently single, 65% said that contact with another person was too exhausting for them, 61% were afraid that they would not be able to fulfil the expectations of a romantic partner, and 57% said that they did not know how they could find and get involved with a partner; and 50% stated that they did not know how a romantic relationship works or how they would be expected to behave in a romantic relationship”

“[P]revious studies that exclusively examined adults with ASD without intellectual impairment reported lower levels of romantic relationship experience than the current study, with numbers varying between 16% and 31% […] The results of our study can be best compared with the results of Hofvander et al. (2009) and Renty and Roeyers (2006): They selected their samples […] using methods that are comparable to ours. Hofvander et al. (2009) found that 16% of their participants have had romantic relationship experience in the past, compared to 29% in our sample; and Renty and Roeyers (2006) report that 28% of their participants were either married or engaged in a romantic relationship at the time of their study, compared to 44% in our study. […] Compared to typically developed individuals the percentage of ASD individuals with a romantic relationship partner is relatively low (Weimann, 2010). In the group aged 27–59 years, 68% of German males live together with a partner, 27% are single, and 5% still live with their parents. In the same age group, 73% of all females live with a partner, 26% live on their own, and 2% still live with their parents.”

“As our results show, it is not the case that male ASD individuals do not feel a need for romantic relationships. In fact, the contrary is true. Single males had a greater desire to be in a romantic relationship than single females, and males were more distressed than females about not being in a romantic relationship.” (…maybe in part because the females who were single were more likely than the males who were single to be single by choice?)

“Our findings showed that being with a partner who also has an ASD diagnosis makes a romantic relationship more satisfying for ASD individuals. None of the participants, who had been with a partner in the past but then separated, had been together with an ASD partner. This might indicate that once a person with ASD has found a partner who is also on the spectrum, a relationship might be very stable and long lasting.”

Reward Processing in Autism.

“The social motivation hypothesis of autism posits that infants with autism do not experience social stimuli as rewarding, thereby leading to a cascade of potentially negative consequences for later development. […] Here we use functional magnetic resonance imaging to examine social and monetary rewarded implicit learning in children with and without autism spectrum disorders (ASD). Sixteen males with ASD and sixteen age- and IQ-matched typically developing (TD) males were scanned while performing two versions of a rewarded implicit learning task. In addition to examining responses to reward, we investigated the neural circuitry supporting rewarded learning and the relationship between these factors and social development. We found diminished neural responses to both social and monetary rewards in ASD, with a pronounced reduction in response to social rewards (SR). […] Moreover, we show a relationship between ventral striatum activity and social reciprocity in TD children. Together, these data support the hypothesis that children with ASD have diminished neural responses to SR, and that this deficit relates to social learning impairments. […] When we examined the general neural response to monetary and social reward events, we discovered that only TD children showed VS [ventral striatum] activity for both reward types, whereas ASD children did not demonstrate a significant response to either monetary or SR. However, significant between-group differences were shown only for SR, suggesting that children with ASD may be specifically impaired on processing SR.”

I’m not quite sure I buy that the methodology captures what it is supposed to capture (“The SR feedback consisted of a picture of a smiling woman with the words “That’s Right!” in green text for correct trials and a picture of the same woman with a sad face along with the words “That’s Wrong” in red text for incorrect trials”) (this is supposed to be the ‘social reward feedback’), but on the other hand: “The chosen reward stimuli, faces and coins, are consistent with those used in previous studies of reward processing” (so either multiple studies are of dubious quality, or this kind of method actually ‘works’ – but I don’t know enough about the field to tell which of the two conclusions apply).

iv. The Social Motivation Theory of Autism.

“The idea that social motivation deficits play a central role in Autism Spectrum Disorders (ASD) has recently gained increased interest. This constitutes a shift in autism research, which has traditionally focused more intensely on cognitive impairments, such as Theory of Mind deficits or executive dysfunction, while granting comparatively less attention to motivational factors. This review delineates the concept of social motivation and capitalizes on recent findings in several research areas to provide an integrated picture of social motivation at the behavioral, biological and evolutionary levels. We conclude that ASD can be construed as an extreme case of diminished social motivation and, as such, provides a powerful model to understand humans’ intrinsic drive to seek acceptance and avoid rejection.”

v. Stalking, and Social and Romantic Functioning Among Adolescents and Adults with Autism Spectrum Disorder.

“We examine the nature and predictors of social and romantic functioning in adolescents and adults with ASD. Parental reports were obtained for 25 ASD adolescents and adults (13-36 years), and 38 typical adolescents and adults (13-30 years). The ASD group relied less upon peers and friends for social (OR = 52.16, p < .01) and romantic learning (OR = 38.25, p < .01). Individuals with ASD were more likely to engage in inappropriate courting behaviours (χ2 df = 19 = 3168.74, p < .001) and were more likely to focus their attention upon celebrities, strangers, colleagues, and ex-partners (χ2 df = 5 =2335.40, p < .001), and to pursue their target longer than controls (t = -2.23, df = 18.79, p < .05).”

“Examination of relationships the individuals were reported to have had with the target of their social or romantic interest, indicated that ASD adolescents and adults sought to initiate fewer social and romantic relationships but across a wider variety of people, such as strangers, colleagues, acquaintances, friends, ex-partners, and celebrities. […] typically developing peers […] were more likely to target colleagues, acquaintances, friends, and ex-partners in their relationship attempts, whilst the ASD group targeted these less frequently than expected, and attempted to initiate relationships significantly more frequently than is typical, with strangers and celebrities. […] In attempting to pursue and initiate social and romantic relationships, the ASD group were reported to display a much wider variety of courtship behaviours than the typical group. […] ASD adolescents and adults were more likely to touch the person of interest inappropriately, believe that the target must reciprocate their feelings, show obsessional interest, make inappropriate comments, monitor the person’s activities, follow them, pursue them in a threatening manner, make threats against the person, and threaten self-harm. ASD individuals displayed the majority of the behaviours indiscriminately across all types of targets. […] ASD adolescents and adults were also found […] to persist in their relationship pursuits for significantly longer periods of time than typical adolescents and adults when they received a negative or no response from the person or their family.”

April 4, 2017 Posted by | autism, Neurology, Papers, Psychology | Leave a comment

Random stuff

It’s been a long time since I last posted one of these posts, so a great number of links of interest has accumulated in my bookmarks. I intended to include a large number of these in this post and this of course means that I surely won’t cover each specific link included in this post in anywhere near the amount of detail it deserves, but that can’t be helped.

i. Autism Spectrum Disorder Grown Up: A Chart Review of Adult Functioning.

“For those diagnosed with ASD in childhood, most will become adults with a significant degree of disability […] Seltzer et al […] concluded that, despite considerable heterogeneity in social outcomes, “few adults with autism live independently, marry, go to college, work in competitive jobs or develop a large network of friends”. However, the trend within individuals is for some functional improvement over time, as well as a decrease in autistic symptoms […]. Some authors suggest that a sub-group of 15–30% of adults with autism will show more positive outcomes […]. Howlin et al. (2004), and Cederlund et al. (2008) assigned global ratings of social functioning based on achieving independence, friendships/a steady relationship, and education and/or a job. These two papers described respectively 22% and 27% of groups of higher functioning (IQ above 70) ASD adults as attaining “Very Good” or “Good” outcomes.”

“[W]e evaluated the adult outcomes for 45 individuals diagnosed with ASD prior to age 18, and compared this with the functioning of 35 patients whose ASD was identified after 18 years. Concurrent mental illnesses were noted for both groups. […] Comparison of adult outcome within the group of subjects diagnosed with ASD prior to 18 years of age showed significantly poorer functioning for those with co-morbid Intellectual Disability, except in the domain of establishing intimate relationships [my emphasis. To make this point completely clear, one way to look at these results is that apparently in the domain of partner-search autistics diagnosed during childhood are doing so badly in general that being intellectually disabled on top of being autistic is apparently conferring no additional disadvantage]. Even in the normal IQ group, the mean total score, i.e. the sum of the 5 domains, was relatively low at 12.1 out of a possible 25. […] Those diagnosed as adults had achieved significantly more in the domains of education and independence […] Some authors have described a subgroup of 15–27% of adult ASD patients who attained more positive outcomes […]. Defining an arbitrary adaptive score of 20/25 as “Good” for our normal IQ patients, 8 of thirty four (25%) of those diagnosed as adults achieved this level. Only 5 of the thirty three (15%) diagnosed in childhood made the cutoff. (The cut off was consistent with a well, but not superlatively, functioning member of society […]). None of the Intellectually Disabled ASD subjects scored above 10. […] All three groups had a high rate of co-morbid psychiatric illnesses. Depression was particularly frequent in those diagnosed as adults, consistent with other reports […]. Anxiety disorders were also prevalent in the higher functioning participants, 25–27%. […] Most of the higher functioning ASD individuals, whether diagnosed before or after 18 years of age, were functioning well below the potential implied by their normal range intellect.”

Related papers: Social Outcomes in Mid- to Later Adulthood Among Individuals Diagnosed With Autism and Average Nonverbal IQ as Children, Adults With Autism Spectrum Disorders.

ii. Premature mortality in autism spectrum disorder. This is a Swedish matched case cohort study. Some observations from the paper:

“The aim of the current study was to analyse all-cause and cause-specific mortality in ASD using nationwide Swedish population-based registers. A further aim was to address the role of intellectual disability and gender as possible moderators of mortality and causes of death in ASD. […] Odds ratios (ORs) were calculated for a population-based cohort of ASD probands (n = 27 122, diagnosed between 1987 and 2009) compared with gender-, age- and county of residence-matched controls (n = 2 672 185). […] During the observed period, 24 358 (0.91%) individuals in the general population died, whereas the corresponding figure for individuals with ASD was 706 (2.60%; OR = 2.56; 95% CI 2.38–2.76). Cause-specific analyses showed elevated mortality in ASD for almost all analysed diagnostic categories. Mortality and patterns for cause-specific mortality were partly moderated by gender and general intellectual ability. […] Premature mortality was markedly increased in ASD owing to a multitude of medical conditions. […] Mortality was significantly elevated in both genders relative to the general population (males: OR = 2.87; females OR = 2.24)”.

“Individuals in the control group died at a mean age of 70.20 years (s.d. = 24.16, median = 80), whereas the corresponding figure for the entire ASD group was 53.87 years (s.d. = 24.78, median = 55), for low-functioning ASD 39.50 years (s.d. = 21.55, median = 40) and high-functioning ASD 58.39 years (s.d. = 24.01, median = 63) respectively. […] Significantly elevated mortality was noted among individuals with ASD in all analysed categories of specific causes of death except for infections […] ORs were highest in cases of mortality because of diseases of the nervous system (OR = 7.49) and because of suicide (OR = 7.55), in comparison with matched general population controls.”

iii. Adhesive capsulitis of shoulder. This one is related to a health scare I had a few months ago. A few quotes:

Adhesive capsulitis (also known as frozen shoulder) is a painful and disabling disorder of unclear cause in which the shoulder capsule, the connective tissue surrounding the glenohumeral joint of the shoulder, becomes inflamed and stiff, greatly restricting motion and causing chronic pain. Pain is usually constant, worse at night, and with cold weather. Certain movements or bumps can provoke episodes of tremendous pain and cramping. […] People who suffer from adhesive capsulitis usually experience severe pain and sleep deprivation for prolonged periods due to pain that gets worse when lying still and restricted movement/positions. The condition can lead to depression, problems in the neck and back, and severe weight loss due to long-term lack of deep sleep. People who suffer from adhesive capsulitis may have extreme difficulty concentrating, working, or performing daily life activities for extended periods of time.”

Some other related links below:

The prevalence of a diabetic condition and adhesive capsulitis of the shoulder.
“Adhesive capsulitis is characterized by a progressive and painful loss of shoulder motion of unknown etiology. Previous studies have found the prevalence of adhesive capsulitis to be slightly greater than 2% in the general population. However, the relationship between adhesive capsulitis and diabetes mellitus (DM) is well documented, with the incidence of adhesive capsulitis being two to four times higher in diabetics than in the general population. It affects about 20% of people with diabetes and has been described as the most disabling of the common musculoskeletal manifestations of diabetes.”

Adhesive Capsulitis (review article).
“Patients with type I diabetes have a 40% chance of developing a frozen shoulder in their lifetimes […] Dominant arm involvement has been shown to have a good prognosis; associated intrinsic pathology or insulin-dependent diabetes of more than 10 years are poor prognostic indicators.15 Three stages of adhesive capsulitis have been described, with each phase lasting for about 6 months. The first stage is the freezing stage in which there is an insidious onset of pain. At the end of this period, shoulder ROM [range of motion] becomes limited. The second stage is the frozen stage, in which there might be a reduction in pain; however, there is still restricted ROM. The third stage is the thawing stage, in which ROM improves, but can take between 12 and 42 months to do so. Most patients regain a full ROM; however, 10% to 15% of patients suffer from continued pain and limited ROM.”

Musculoskeletal Complications in Type 1 Diabetes.
“The development of periarticular thickening of skin on the hands and limited joint mobility (cheiroarthropathy) is associated with diabetes and can lead to significant disability. The objective of this study was to describe the prevalence of cheiroarthropathy in the well-characterized Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort and examine associated risk factors […] This cross-sectional analysis was performed in 1,217 participants (95% of the active cohort) in EDIC years 18/19 after an average of 24 years of follow-up. Cheiroarthropathy — defined as the presence of any one of the following: adhesive capsulitis, carpal tunnel syndrome, flexor tenosynovitis, Dupuytren’s contracture, or a positive prayer sign [related link] — was assessed using a targeted medical history and standardized physical examination. […] Cheiroarthropathy was present in 66% of subjects […] Cheiroarthropathy is common in people with type 1 diabetes of long duration (∼30 years) and is related to longer duration and higher levels of glycemia. Clinicians should include cheiroarthropathy in their routine history and physical examination of patients with type 1 diabetes because it causes clinically significant functional disability.”

Musculoskeletal disorders in diabetes mellitus: an update.
“Diabetes mellitus (DM) is associated with several musculoskeletal disorders. […] The exact pathophysiology of most of these musculoskeletal disorders remains obscure. Connective tissue disorders, neuropathy, vasculopathy or combinations of these problems, may underlie the increased incidence of musculoskeletal disorders in DM. The development of musculoskeletal disorders is dependent on age and on the duration of DM; however, it has been difficult to show a direct correlation with the metabolic control of DM.”

Rheumatic Manifestations of Diabetes Mellitus.

Prevalence of symptoms and signs of shoulder problems in people with diabetes mellitus.

Musculoskeletal Disorders of the Hand and Shoulder in Patients with Diabetes.
“In addition to micro- and macroangiopathic complications, diabetes mellitus is also associated with several musculoskeletal disorders of the hand and shoulder that can be debilitating (1,2). Limited joint mobility, also termed diabetic hand syndrome or cheiropathy (3), is characterized by skin thickening over the dorsum of the hands and restricted mobility of multiple joints. While this syndrome is painless and usually not disabling (2,4), other musculoskeletal problems occur with increased frequency in diabetic patients, including Dupuytren’s disease [“Dupuytren’s disease […] may be observed in up to 42% of adults with diabetes mellitus, typically in patients with long-standing T1D” – link], carpal tunnel syndrome [“The prevalence of [carpal tunnel syndrome, CTS] in patients with diabetes has been estimated at 11–30 % […], and is dependent on the duration of diabetes. […] Type I DM patients have a high prevalence of CTS with increasing duration of disease, up to 85 % after 54 years of DM” – link], palmar flexor tenosynovitis or trigger finger [“The incidence of trigger finger [/stenosing tenosynovitis] is 7–20 % of patients with diabetes comparing to only about 1–2 % in nondiabetic patients” – link], and adhesive capsulitis of the shoulder (5–10). The association of adhesive capsulitis with pain, swelling, dystrophic skin, and vasomotor instability of the hand constitutes the “shoulder-hand syndrome,” a rare but potentially disabling manifestation of diabetes (1,2).”

“The prevalence of musculoskeletal disorders was greater in diabetic patients than in control patients (36% vs. 9%, P < 0.01). Adhesive capsulitis was present in 12% of the diabetic patients and none of the control patients (P < 0.01), Dupuytren’s disease in 16% of diabetic and 3% of control patients (P < 0.01), and flexor tenosynovitis in 12% of diabetic and 2% of control patients (P < 0.04), while carpal tunnel syndrome occurred in 12% of diabetic patients and 8% of control patients (P = 0.29). Musculoskeletal disorders were more common in patients with type 1 diabetes than in those with type 2 diabetes […]. Forty-three patients [out of 100] with type 1 diabetes had either hand or shoulder disorders (37 with hand disorders, 6 with adhesive capsulitis of the shoulder, and 10 with both syndromes), compared with 28 patients [again out of 100] with type 2 diabetes (24 with hand disorders, 4 with adhesive capsulitis of the shoulder, and 3 with both syndromes, P = 0.03).”

Association of Diabetes Mellitus With the Risk of Developing Adhesive Capsulitis of the Shoulder: A Longitudinal Population-Based Followup Study.
“A total of 78,827 subjects with at least 2 ambulatory care visits with a principal diagnosis of DM in 2001 were recruited for the DM group. The non-DM group comprised 236,481 age- and sex-matched randomly sampled subjects without DM. […] During a 3-year followup period, 946 subjects (1.20%) in the DM group and 2,254 subjects (0.95%) in the non-DM group developed ACS. The crude HR of developing ACS for the DM group compared to the non-DM group was 1.333 […] the association between DM and ACS may be explained at least in part by a DM-related chronic inflammatory process with increased growth factor expression, which in turn leads to joint synovitis and subsequent capsular fibrosis.”

It is important to note when interpreting the results of the above paper that these results are based on Taiwanese population-level data, and type 1 diabetes – which is obviously the high-risk diabetes subgroup in this particular context – is rare in East Asian populations (as observed in Sperling et al., “A child in Helsinki, Finland is almost 400 times more likely to develop diabetes than a child in Sichuan, China”. Taiwanese incidence of type 1 DM in children is estimated at ~5 in 100.000).

iv. Parents who let diabetic son starve to death found guilty of first-degree murder. It’s been a while since I last saw one of these ‘boost-your-faith-in-humanity’-cases, but they in my impression do pop up every now and then. I should probably keep at hand one of these articles in case my parents ever express worry to me that they weren’t good parents; they could have done a lot worse…

v. Freedom of medicine. One quote from the conclusion of Cochran’s post:

“[I]t is surely possible to materially improve the efficacy of drug development, of medical research as a whole. We’re doing better than we did 500 years ago – although probably worse than we did 50 years ago. But I would approach it by learning as much as possible about medical history, demographics, epidemiology, evolutionary medicine, theory of senescence, genetics, etc. Read Koch, not Hayek. There is no royal road to medical progress.”

I agree, and I was considering including some related comments and observations about health economics in this post – however I ultimately decided against doing that in part because the post was growing unwieldy; I might include those observations in another post later on. Here’s another somewhat older Westhunt post I at some point decided to bookmark – I in particular like the following neat quote from the comments, which expresses a view I have of course expressed myself in the past here on this blog:

“When you think about it, falsehoods, stupid crap, make the best group identifiers, because anyone might agree with you when you’re obviously right. Signing up to clear nonsense is a better test of group loyalty. A true friend is with you when you’re wrong. Ideally, not just wrong, but barking mad, rolling around in your own vomit wrong.”

vi. Economic Costs of Diabetes in the U.S. in 2012.

“Approximately 59% of all health care expenditures attributed to diabetes are for health resources used by the population aged 65 years and older, much of which is borne by the Medicare program […]. The population 45–64 years of age incurs 33% of diabetes-attributed costs, with the remaining 8% incurred by the population under 45 years of age. The annual attributed health care cost per person with diabetes […] increases with age, primarily as a result of increased use of hospital inpatient and nursing facility resources, physician office visits, and prescription medications. Dividing the total attributed health care expenditures by the number of people with diabetes, we estimate the average annual excess expenditures for the population aged under 45 years, 45–64 years, and 65 years and above, respectively, at $4,394, $5,611, and $11,825.”

“Our logistic regression analysis with NHIS data suggests that diabetes is associated with a 2.4 percentage point increase in the likelihood of leaving the workforce for disability. This equates to approximately 541,000 working-age adults leaving the workforce prematurely and 130 million lost workdays in 2012. For the population that leaves the workforce early because of diabetes-associated disability, we estimate that their average daily earnings would have been $166 per person (with the amount varying by demographic). Presenteeism accounted for 30% of the indirect cost of diabetes. The estimate of a 6.6% annual decline in productivity attributed to diabetes (in excess of the estimated decline in the absence of diabetes) equates to 113 million lost workdays per year.”

vii. Total red meat intake of ≥0.5 servings/d does not negatively influence cardiovascular disease risk factors: a systemically searched meta-analysis of randomized controlled trials.

viii. Effect of longer term modest salt reduction on blood pressure: Cochrane systematic review and meta-analysis of randomised trials. Did I blog this paper at some point in the past? I could not find any coverage of it on the blog when I searched for it so I decided to include it here, even if I have a nagging suspicion I may have talked about these findings before. What did they find? The short version is this:

“A modest reduction in salt intake for four or more weeks causes significant and, from a population viewpoint, important falls in blood pressure in both hypertensive and normotensive individuals, irrespective of sex and ethnic group. Salt reduction is associated with a small physiological increase in plasma renin activity, aldosterone, and noradrenaline and no significant change in lipid concentrations. These results support a reduction in population salt intake, which will lower population blood pressure and thereby reduce cardiovascular disease.”

ix. Some wikipedia links:

Heroic Age of Antarctic Exploration (featured).

Wien’s displacement law.

Kuiper belt (featured).

Treason (one quote worth including here: “Currently, the consensus among major Islamic schools is that apostasy (leaving Islam) is considered treason and that the penalty is death; this is supported not in the Quran but in the Hadith.[42][43][44][45][46][47]“).

Lymphatic filariasis.

File:World map of countries by number of cigarettes smoked per adult per year.

Australian gold rushes.

Savant syndrome (“It is estimated that 10% of those with autism have some form of savant abilities”). A small sidenote of interest to Danish readers: The Danish Broadcasting Corporation recently featured a series about autistics with ‘special abilities’ – the show was called ‘The hidden talents’ (De skjulte talenter), and after multiple people had nagged me to watch it I ended up deciding to do so. Most of the people in that show presumably had some degree of ‘savantism’ combined with autism at the milder end of the spectrum, i.e. Asperger’s. I was somewhat conflicted about what to think about the show and did consider blogging it in detail (in Danish?), but I decided against it. However I do want to add here to Danish readers reading along who’ve seen the show that they would do well to repeatedly keep in mind that a) the great majority of autistics do not have abilities like these, b) many autistics with abilities like these presumably do quite poorly, and c) that many autistics have even greater social impairments than do people like e.g. (the very likeable, I have to add…) Louise Wille from the show).

Quark–gluon plasma.

Simo Häyhä.

Chernobyl liquidators.

Black Death (“Over 60% of Norway’s population died in 1348–1350”).

Renault FT (“among the most revolutionary and influential tank designs in history”).

Weierstrass function (“an example of a pathological real-valued function on the real line. The function has the property of being continuous everywhere but differentiable nowhere”).

W Ursae Majoris variable.

Void coefficient. (“a number that can be used to estimate how much the reactivity of a nuclear reactor changes as voids (typically steam bubbles) form in the reactor moderator or coolant. […] Reactivity is directly related to the tendency of the reactor core to change power level: if reactivity is positive, the core power tends to increase; if it is negative, the core power tends to decrease; if it is zero, the core power tends to remain stable. […] A positive void coefficient means that the reactivity increases as the void content inside the reactor increases due to increased boiling or loss of coolant; for example, if the coolant acts as a neutron absorber. If the void coefficient is large enough and control systems do not respond quickly enough, this can form a positive feedback loop which can quickly boil all the coolant in the reactor. This happened in the RBMK reactor that was destroyed in the Chernobyl disaster.”).

Gregor MacGregor (featured) (“a Scottish soldier, adventurer, and confidence trickster […] MacGregor’s Poyais scheme has been called one of the most brazen confidence tricks in history.”).

Stimming.

Irish Civil War.

March 10, 2017 Posted by | Astronomy, autism, Cardiology, Diabetes, Economics, Epidemiology, Health Economics, History, Infectious disease, Mathematics, Medicine, Papers, Physics, Psychology, Random stuff, Wikipedia | Leave a comment

Role of Biomarkers in Medicine

“The use of biomarkers in basic and clinical research has become routine in many areas of medicine. They are accepted as molecular signatures that have been well characterized and repeatedly shown to be capable of predicting relevant disease states or clinical outcomes. In Role of Biomarkers in Medicine, expert researchers in their individual field have reviewed many biomarkers or potential biomarkers in various types of diseases. The topics address numerous aspects of medicine, demonstrating the current conceptual status of biomarkers as clinical tools and as surrogate endpoints in clinical research.”

The above quote is from the preface of the book. Here’s my goodreads review. I have read about biomarkers before – for previous posts on this topic, see this link. I added the link in part because the coverage provided in this book is in my opinion generally of a somewhat lower quality than is the coverage that has been provided in some of the other books I’ve read on these topics. However the fact that the book is not amazing should probably not keep me from sharing some observations of interest from the book, which I have done in this post.

we suggest more precise studies to establish the exact role of this hormone […] additional studies are necessary […] there are conflicting results […] require further investigation […] more intervention studies with long-term follow-up are required. […] further studies need to be conducted […] further research is needed (There are a lot of comments like these in the book, I figured I should include a few in my coverage…)

“Cancer biomarkers (CB) are biomolecules produced either by the tumor cells or by other cells of the body in response to the tumor, and CB could be used as screening/early detection tool of cancer, diagnostic, prognostic, or predictor for the overall outcome of a patient. Moreover, cancer biomarkers may identify subpopulations of patients who are most likely to respond to a given therapy […] Unfortunately, […] only very few CB have been approved by the FDA as diagnostic or prognostic cancer markers […] 25 years ago, the clinical usefulness of CB was limited to be an effective tool for patient’s prognosis, surveillance, and therapy monitoring. […] CB have [since] been reported to be used also for screening of general population or risk groups, for differential diagnosis, and for clinical staging or stratification of cancer patients. Additionally, CB are used to estimate tumor burden and to substitute for a clinical endpoint and/or to measure clinical benefit, harm or lack of benefit, or harm [4, 18, 30]. Among commonly utilized biomarkers in clinical practice are PSA, AFP, CA125, and CEA.”

“Bladder cancer (BC) is the second most common malignancy in the urologic field. Preoperative predictive biomarkers of cancer progression and prognosis are imperative for optimizing […] treatment for patients with BC. […] Approximately 75–85% of BC cases are diagnosed as nonmuscle-invasive bladder cancer (NMIBC) […] NMIBC has a tendency to recur (50–70%) and may progress (10–20%) to a higher grade and/or muscle-invasive BC (MIBC) in time, which can lead to high cancer-specific mortality [2]. Histological tumor grade is one of the clinical factors associated with outcomes of patients with NMIBC. High-grade NMIBC generally exhibits more aggressive behavior than low-grade NMIBC, and it increases the risk of a poorer prognosis […] Cystoscopy and urine cytology are commonly used techniques for the diagnosis and surveillance of BC. Cystoscopy can identify […] most papillary and solid lesions, but this is highly invasive […] urine cytology is limited by examiner experience and low sensitivity. For these reasons, some tumor markers have been investigated […], but their sensitivity and specificity are limited [5] and they are unable to predict the clinical outcome of BC patients. […] Numerous efforts have been made to identify tumor markers. […] However, a serum marker that can serve as a reliable detection marker for BC has yet to be identified.”

“Endometrial cancer (EmCa) is the most common type of gynecological cancer. EmCa is the fourth most common cancer in the United States, which has been linked to increased incidence of obesity. […] there are no reliable biomarker tests for early detection of EmCa and treatment effectiveness. […] Approximately 75% of women with EmCa are postmenopausal; the most common symptom is postmenopausal bleeding […] Approximately 15% of women diagnosed with EmCa are younger than 50 years of age, while 5% are diagnosed before the age of 40 [29]. […] Roughly, half of the EmCa cases are linked to obesity. Obese women are four times more likely to develop EmCa when compared to normal weight women […] Obese individuals oftentimes exhibit resistance to leptin and show high levels of the adipokine in blood, which is known as leptin resistance […] prolonged exposure of leptin damages the hypothalamus causing it to become insensitive to the effects of leptin […] Evidence shows that leptin is an important pro-inflammatory, pro-angiogenic, and mitogenic factor for cancer. Leptin produced by cancer cells acts in an autocrine and paracrine manner to promote tumor cell proliferation, migration and invasion, pro-inflammation, and angiogenesis [58, 70]. High levels of leptin […] are associated with metastasis and decreased survival rates in breast cancer patients [58]. […] Metabolic syndrome including obesity, hypertension, insulin resistance, diabetes, and dyslipidemia increase the risk of developing multiple malignancies, particularly EmCa [30]. Younger women diagnosed with EmCa are usually obese, and their carcinomas show a well-differentiated histology [20].

“Normally, tumor suppressor genes act to inhibit or arrest cell proliferation and tumor development [37]. However; when mutated, tumor suppressors become inactive, thus permitting tumor growth. For example, mutations in p53 have been determined in various cancers such as breast, colon, lung, endometrium, leukemias, and carcinomas of many tissues. These p53 mutations are found in approximately 50% of all cancers [38]. Roughly 10–20% of endometrial carcinomas exhibit p53 mutations [37]. […] overexpression of mutated tumor suppressor p53 has been associated with Type II EmCa (poor histologic grade, non-endometrioid histology, advanced stage, and poor survival).”

“Increasing data indicate that oxidative stress is involved in the development of DR [diabetic retinopathy] [16–19]. The retina has a high content of polyunsaturated fatty acids and has the highest oxygen uptake and glucose oxidation relative to any other tissue. This phenomenon renders the retina more susceptible to oxidative stress [20]. […] Since long-term exposure to oxidative stress is strongly implicated in the pathogenesis of diabetic complications, polymorphic genes of detoxifying enzymes may be involved in the development of DR. […] A meta-analysis comprising 17 studies, including type 1 and type 2 diabetic patients from different ethnic origins, implied that the C (Ala) allele of the C47T polymorphism in the MnSOD gene had a significant protective effect against microvascular complications (DR and diabetic nephropathy) […] In the development of DR, superoxide levels are elevated in the retina, antioxidant defense system is compromised, MnSOD is inhibited, and mitochondria are swollen and dysfunctional [77,87–90]. Overexpression of MnSOD protects [against] diabetes-induced mitochondrial damage and the development of DR [19,91].”

Continuous high level of blood glucose in diabetes damages micro and macro blood vessels throughout the body by altering the endothelial cell lining of the blood vessels […] Diabetes threatens vision, and patients with diabetes develop cataracts at an earlier age and are nearly twice as likely to get glaucoma compared to non-diabetic[s] [3]. More than 75% of patients who have had diabetes mellitus for more than 20 years will develop diabetic retinopathy (DR) [4]. […] DR is a slow progressive retinal disease and occurs as a consequence of longstanding accumulated functional and structural impairment of the retina by diabetes. It is a multifactorial condition arising from the complex interplay between biochemical and metabolic abnormalities occurring in all cells of the retina. DR has been classically regarded as a microangiopathy of the retina, involving changes in the vascular wall leading to capillary occlusion and thereby retinal ischemia and leakage. And more recently, the neural defects in the retina are also being appreciated […]. Recently, various clinical investigators [have detected] neuronal dysfunction at very early stages of diabetes and numerous abnormalities in the retina can be identified even before the vascular pathology appears [76, 77], thus suggesting a direct effect of diabetes on the neural retina. […] An emerging issue in DR research is the focus on the mechanistic link between chronic low-grade inflammation and angiogenesis. Recent evidence has revealed that extracellular high-mobility group box-1 (HMGB1) protein acts as a potent proinflammatory cytokine that triggers inflammation and recruits leukocytes to the site of tissue damage, and exhibits angiogenic effects. The expression of HMGB1 is upregulated in epiretinal membranes and vitreous fluid from patients with proliferative DR and in the diabetic retina. […] HMGB1 may be a potential biomarker [for diabetic retinopathy] […] early blockade of HMGB1 may be an effective strategy to prevent the progression of DR.”

“High blood pressure is one of the leading risk factors for global mortality and is estimated to have caused 9.4 million deaths in 2010. A meta‐analysis which includes 1 million individuals has indicated that death from both CHD [coronary heart disease] and stroke increase progressively and linearly from BP levels as low as 115 mmHg systolic and 75 mmHg diastolic upwards [138]. The WHO [has] pointed out that a “reduction in systolic blood pressure of 10 mmHg is associated with a 22% reduction in coronary heart disease, 41% reduction in stroke in randomized trials, and a 41–46% reduction in cardiometabolic mortality in epidemiological studies” [139].”

Several reproducible studies have ascertained that individuals with autism demonstrate an abnormal brain 5-HT system […] peripheral alterations in the 5-HT system may be an important marker of central abnormalities in autism. […] In a recent study, Carminati et al. [129] tested the therapeutic efficacy of venlafaxine, an antidepressant drug that inhibits the reuptake of 5-HT, and [found] that venlafaxine at a low dose [resulted in] a substantial improvement in repetitive behaviors, restricted interests, social impairment, communication, and language. Venlafaxine probably acts via serotonergic mechanisms  […] OT [Oxytocin]-related studies in autism have repeatedly reported lower blood OT level in autistic patients compared to age- and gender-matched control subjects […] autistic patients demonstrate an altered neuroinflammatory response throughout their lives; they also show increased astrocyte and microglia inflammatory response in the cortex and the cerebellum  [47, 48].”

November 3, 2016 Posted by | autism, Books, Cancer/oncology, Cardiology, Diabetes, Epidemiology, Genetics, Immunology, Medicine, Neurology, Ophthalmology, Pharmacology | Leave a comment

Nonverbal Communication

“The purpose of the book is to bring together a number of nonverbal behavior researchers to discuss current themes and research. The book is meant for senior undergraduates, graduates, academics and nonverbal communication researchers, as well as for everyone else who wants to interpret and understand better nonverbal behavior and the states of their interlocutors. The texts in this book show the results of contemporary research and theorization of the nature, functions, and modalities of nonverbal behavior in different areas of life.”

From the introduction of the book. The book has two parts; a theoretical part and an applied part. The first half of the book covers theoretical research and as I also noted in my goodreads review I found this part of the book quite weak, but a few of the chapters in the second half of the book, dealing with applied research into these topics, had some interesting stuff (‘If you decide to have a go at this book I’d probably be tempted to recommend only reading the first four chapters of part 2’ – from my goodreads review). My coverage of the book in this post will skip a lot of chapters; I’ll focus on the stuff I found interesting and just ignore the rest. The four chapters mentioned above cover ‘Nonverbal Firsts: When Nonverbal Cues Are the Impetus of Relational and Personal Change in Romantic Relationships’ (chapter 7), ‘Beyond Facial Expression: Spatial Distance as a Factor in the Communication of Discrete Emotions’ (chapter 8), Theoretical Foundation for Emotion-Based Strategies in Political Campaigns (chapter 9), and ‘The Impact of Nonverbal Behavior in the Job Interview’ (chapter 10).

I would note that I actually emailed a few quotes from the last of these chapters to a good friend of mine who recently had a job interview coming up, which is perhaps a good illustration of how potentially useful I consider some of the content covered here to be – this is worth keeping in mind when interpreting the two star (and ‘much closer to one star than three’) goodreads rating. It should however also be recalled that the authors of chapter 8, which is incidentally far from the worst chapter in the book, claim/think the so-called McClintock effect is real, based on outdated research. They write in the chapter that: “Martha McClintock and colleagues reported evidence that the menstrual cycles of co-habiting women can become synchronized, a phenomenon termed the McClintock effect (McClintock, 1971; Hummer & McClintock, 2009). Although controversial, the reality of the phenomenon is now generally accepted (Wysocki & Preti, 2004).” Compare with wikipedia: “A 2013 review of menstrual synchrony concluded that menstrual synchrony is an erroneous theory. […] Harris and Vitzthum concluded, “In light of the lack of empirical evidence for MS [menstrual synchrony] sensu stricto, it seems there should be more widespread doubt than acceptance of this hypothesis””.

Below I have added some quotes from the book, as well as a few observations of my own. I would note that I have read and written about stuff related to the content covered in this post before here on the blog, so if you’re curious to learn more after having read this post, you might consider following some of those links.

“[N]onverbal behaviors have the potential to be transformative. That is, they may act as triggers for a change in a relationship, perception, behavior, or affect. In particular, […] when a nonverbal behavior occurs or is noticed for the first time, these behavioral “firsts” can have big implications, positive or negative, for people in relationships. […] the authors find that touch, eye behavior, and personal space are the cues reported most commonly as triggers for change and which help bring about the start of a romantic relationship, perception of how much or little another cares, relational problems, instant break-ups, and indicators of another’s untrustworthiness.”

“Baxter and Bullis (1986) found that the first time their participants kissed or had sex with a partner altered the degree of commitment that they had to the relationship. In this way, the first appearance of certain nonverbal cues or acts may be important triggers of change within a relationship. […] In our respondents’ reports, we read many accounts of how a single behavior, used for what the respondent recalled was the first time, instantly changed the relationship or the perception of the relationship between the two individuals. There was some variety in the behaviors, but most typically they were handholding, prolonged gaze, kisses, closer proximity, and “changes” in touch behavior. In most of the situations described by our participants, the behavior was received positively and started a romantic relationship. In a few instances, however, it indicated to the respondent that they or another person had romantic feelings that were unreciprocated. These latter situations reportedly resulted in either the termination of the existing relationship or awkwardness in the relationship. […] the same actions – kisses, close personal distance – may have very different outcomes, depending on the reciprocity of the behaviors and feelings. […] a rather common claim about touch is that it “is a signal in the communication process that, above all other communication channels, most directly and immediately escalates the balance of intimacy” […]. Perhaps above all other nonverbal cues, touch has been shown to facilitate dramatic “surge[s] in affective involvement” […] nonverbal cues, although sometimes subtle and easy to miss, may actually be “big” actions in relational change.”

“[P]articipants often commented on the lack of a behavior (e.g., no eye contact, ignoring behavior [which presumably was determined by lack of gaze, not responding, and the like], and not talking [silence]). The themes were consistent whether they were discussing their own or their partner’s behaviors. […] Avoidance of eye contact, silence, and “ignoring,” rather than immediate, engaged, intimate, behavior was common in this group of entries and marked the beginning (or the first signal) of the relationship’s decline.”

The research they presented in the chapter was disappointing to me in a way, due to the methodology applied. Basically they asked people (…well, psychology undergrads…) which non-verbal behaviours ‘stood out’ to them, and then they interpreted the behaviours based on these accounts. Recall biases are a potentially serious problem, and if you ask people to explain relationship changes as a function of nonverbal behaviours then you’ll probably get answers indicating that nonverbal behaviours are important, regardless of whether they really are or not. But on a related note it seems hard to do ‘naturalistic/observational’ research into these topics (‘follow people around with video cameras and try to spot which nonverbal behaviours on display might be associated with relationship formation?’), and even if the self-reports are not wholly reliable they may provide some information. A big problem in the context of research into these things is of course that you can’t really directly observe relationships and relationship formation; these things are to a very large extent nothing but mental constructs in the minds of the people involved, meaning that you probably to some extent sort of have to rely on things like self-report variables. This makes everything quite a bit more ‘fuzzy’ than it otherwise would be. Note that the fact that ‘relationships are mental constructs existing only in the minds of the people involved’ does not to me seem to necessarily indicate that asking people what they think caused a relationship to change will yield reliable answers; people may not know why they feel the way they do about a given individual or why their feelings changed at some point, and/but if you give them a specific reason/variable to consider they’ll be likely to overestimate the importance of said variable. If they’d asked the same people if specific verbal exchanges (‘first time he said ‘I love you’?’) had changed how they felt about that individual, they might have got different answers.

When you consider how ‘squishy’ this stuff is, I think other approaches besides the ones considered by the authors might also be useful to consider if you want to get at the extent to which nonverbal behaviour is important; for example I feel tempted to conclude that the poor relationship outcomes of autistics (“In terms of outcome studies to date, very few adults with ASD have been reported to have successful, long-term romantic relationships […] Between 10 and 30 % of adults in recent studies […] had experience in a romantic relationship.” – link), a population including people who often have great difficulties interpreting nonverbal behaviours and cues, might provide stronger evidence in favour of the importance of nonverbal behaviours in relationship contexts than the study in question provides. Although I’d certainly agree that important confounders are present in this context (…as well), making it very difficult to take the poor relationship outcomes of this group as solely a consequence of nonverbal behavioural aspects.

“[In political contexts,] candidates and issues that emphasize freedom (e.g., fewer restrictions and external constraints on behavior and opportunities, less limitation on social and economic mobility) are more likely to appeal to men than to women. […] political messages or tactics that repeatedly produce anxious feelings (e.g., bewilderment, distress, pain, insecurity, fear) in voters are likely to magnify the influence of voter emotions on voter political judgments. Additional related effects are expected to include greater polarization of competing groups and simplification of decision rules and belief systems (e.g., increased single-issue voting, greater reliance on candidates’ physical features and communication styles than on candidates’ ideological positions).”

“Research shows that there is a positive relation between [job] applicant positive nonverbal behavior and recruiter evaluation. Positive nonverbal behavior can be defined as immediacy behavior which elicits proximity and liking in the interaction partner as for example a high level of eye contact, smiling, confirmative nodding, hand gestures, and variation in pitch and speaking rate […]. Applicants who used more immediacy behavior (i.e., eye contact, smiling, body orientation toward interviewer, less personal distance) were perceived as being more suitable for the job, more competent, more motivated, and more successful than applicants using less immediacy behavior […] Forbes and Jackson (1980) showed that selected applicants maintained more direct eye contact, smiled more, and nodded more during the job interview than applicants who were not selected for the job. Moreover, applicants who maintained a high amount of eye contact with the recruiter, who showed a high energy level, were affective, modulated their voice, and spoke fluently during the job interview were more likely to be invited for a second job interview than applicants revealing less of those nonverbal behaviors”.

“In terms of applicant characteristics, applicants high in communication apprehension who used more nonverbal avoidance behavior (i.e., less talking, less eye contact, less fluent talking) were less effective in mock job interviews and were perceived as less suitable for the job than applicants with low levels of communication apprehension […] Overall, there are only few studies that did not show an effect between applicant nonverbal immediacy behavior and a favorable hiring decision […] and meta-analyses reveal a clear net effect showing that the more the applicant uses nonverbal immediacy behavior, the better the interview outcome for the applicant (i.e., better chances of getting hired or of being evaluated positively) […] Applicant nonverbal behavior seems to have a remarkable impact on the job interview outcome. The more immediacy (or positive) nonverbal behavior the applicant shows during the job interview, the more positive recruiter evaluations of the applicant are.”

“the question can be asked how accurate recruiters are when inferring applicant characteristics. For many personality characteristics, they seem to use the “wrong,” meaning non-diagnostic, cues. […] many more nonverbal cues are used to infer applicant’s personality traits than are cues actually revealing these traits. […] recruiters seem to use the nonverbal cues that are not diagnostic to assess applicants – in a sense they use the wrong cues – and [yet] are still accurate in assessing applicants’ personality. It remains therefore largely unknown how the recruiters make those correct inferences.”

How accurate the inferences are is to some extent an open question (though it’s probably safe to say that interviews provide less relevant information than many people think – including the authors of that chapter: “[interviews] provide very little unique information about a candidate and show little incremental validity over established psychometric tests (of ability and personality) in the prediction of future job performance […] All sorts of extraneous factors like the perfume a person wears at interview have been shown to influence ratings.” – link). A related observation is that assessment accuracy definitely depends upon the dimension of the variable of interest; some personality characteristics are much easier to observe/deduce than are others, as noted e.g. in Funder’s (‘some behaviors are more dependent on the situation than are others’) book (‘traits like extraversion and agreeableness are the ones most likely to become visible in overt social behavior’).

February 17, 2016 Posted by | autism, Books, Psychology | Leave a comment

Providing practical support for people with autism spectrum disorder – supported living in the community

I actually wasn’t planning on blogging this book because of how disappointing it was. Here’s what I wrote in my goodreads review:

“The last few chapters managed to almost push me all the way towards giving the book one star. You can’t just claim in a book like this that very expensive and comprehensive support systems which you’re dreaming about are cost-effective without citing a single study, especially not in a context where you’ve just claimed that activities which usually end up costing a lot of money will end up saving money. If you envision a much more comprehensive support system, you can’t not address obvious cost drivers.

Some interesting stuff and important observations are included in the book, but the level of coverage is not high and you should not take my two star (‘ok’) rating to indicate that I am in agreement with the author. The main reason why I ended up finishing it was that it was easy to read, not that it was a good book.”

There are no inline citations, and examples of things people with ASD might need help with and ways to help them with these problems seem to be derived from anecdotes, not systematic research. The author repeatedly emphasizes that aid should be individualized and focused on the specific needs of the person with ASD, and although this makes a lot of sense it also makes recommendations very difficult to evaluate (it’s a bit like figuring out what’s going on in the context of other areas of psychological research, where therapists will often ‘mix methods’ when dealing with specific individuals, making it impossible to figure out which components of the treatment regime are actually helpful and which are not because even if people were to try to figure this out, power issues would make it impossible to estimate the relevant interaction effects even in theory); though it should be made clear that the author makes no attempt to do this.

I however found some of the observations included and specific points raised in the book to be interesting, and I’ll mention some of these in the coverage below.

“Professional support needs to be developed and executed in partnership with people and families. For support to be successful, all concerned need to be aware of its objectives and agree with the plan and strategies involved.”

I decided to start out the coverage with this quote because the book is full of postulates like these. Often specific cases will be used to illustrate points like these, but don’t expect any references to actual research on such topics – it’s not that kind of book. The approach employed makes the book incredibly hard for me to evaluate; some of the ideas are presumably sound, but it’s difficult to tell which because they didn’t do the research. In theory it’s sometimes easy to see how a given approach mentioned might lead to, or solve, specific problems, but you’ll often get the idea that perhaps there are tradeoffs at play here which the advice included does not take into account, meaning that in specific cases an alternative solution/piece of advice to the one proposed might lead to better outcomes by trading off the problems associated with the approach mentioned and the problems associated with an alternative approach. In some cases you perhaps would ideally prefer the parents of an adult child living outside the home of the parents to not have too much influence on support strategies employed even though they might traditionally have had a significant role to play in the context of support provision, because the family’s approach to problem solving might be counterproductive, in which case a support plan not supported by the parents might still in some cases be preferable to one which would be supported by them. The emphasis on individualized care throughout the book is, it must be said, on the other hand helpful in terms of thinking about such potential problems, but you still have this impression that a lot of the suggestions in the book are really not based on anywhere near a sufficient amount of data or research, and although they’re often ‘common sense suggestions’ it’s quite clear from a lot of different areas of psychological research by now that common sense can sometimes deceive us.

A general problem I have with the book is, I think, that I think the author is too confident about which support approaches/strategies/etc. might, or might not, work – and perhaps a key reason why she seems overconfident is that she’s not provided the research results in the book which one would in my opinion need in order to draw conclusions like the ones she draws, regardless of whether such research actually exists. A related problem is that quite a few of the concluding statements in the book are at least partly normative statements (which I generally dislike to encounter in non-fiction), not descriptive statements (which I do like to encounter). In the book she repeatedly makes claims about what people with ASD are like without referring to research on these topics, so you’re wondering how she knows these things, and whether or not those claims are actually true, or just true for a small subset of people with ASD which she’s encountered or read about. Many of the observations seemed familiar to me (having encountered them either in other textbooks, or having personal experience with the issues mentioned) so I’d be likely to grant that many of the observations are valid, but you are sometimes wondering how she knows the things she claims to know. A big problem is actually the way she covers the material; she covers various topics in various chapters, but the way she does is makes it relatively hard for a reader to know which parts of a given chapter might actually be useful for a specific individual curious about these things; another way to do things might have been to split the coverage up into chapters about support provision for people with low support requirements, and other chapters about support provision for people with high support requirements. It’s made clear in the book that needs are different for different individuals, but you’re often sort of wondering which passages are most relevant to which groups of people with ASD. One might argue that ‘people ought to be able to tell this on their own’, but then we get to the problems that people with ASD tend to be bad at asking for support, perhaps not realizing that they need it, and the problem that people without ASD who do not know much about ASD perhaps have a difficult time figuring out which types of help might be useful in a specific setting. This stuff is difficult as it is, but I don’t think the way the coverage is structured in this book is helping at all with solving these sorts of issues.

Oh well, let’s move on…:

“The ultimate aim of support should be to improve skills and develop strategies to enable the person with ASD to feel in control and better able to cope independently.”

“The fact is that extremely able people with ASD frequently struggle with day-to-day life skills. Very intelligent students cannot organize themselves to launder their clothes, and may get up to find they are all dirty or still wet in the machine from several days ago. This is one of those superficially trivial things that can be a major problem to the person it repeatedly happens to. On a practical domestic front, what may be a massive difficulty for a person with ASD, may be an easily solved problem for someone without it. […] People with ASD like to have regular routines. The ability to adhere to routine is an advantage in many situations, and this skill can be used productively. Structure and organization can be brought to running the household. As a plan is constructed, problems can be considered and systems put in place to deal with them. A planning session when the individual collaborates with support to work out a weekly menu and the necessary shopping plan, gives the person more autonomy, than having someone turn up to go shopping or cook with them. Having someone alongside is sometimes necessary, but has the disadvantage of creating dependence. The individual is empowered instead by being facilitated to complete tasks independently. […] The best support methods promote independence. […] The aspects of forward planning can be incredibly challenging for a person with ASD, regardless of their intellectual level. […] As people with ASD have great difficulty seeing consequences or planning ahead, they may find it hard to become motivated if the gratification is not instant. Things have to be broken down and explained in a practical way.”

“Most people instigate minor changes easily. It may be more convenient to vary a normal routine on a particular day, even pleasurable. I might decide that as it is a sunny day I will go out, and do the housework in the evening. As a supporter for someone with ASD it is vital to remember, that he will not have the flexibility of thought that people generally have and so may need routines to be more stringently adhered to. Such a simple adjustment may not be easy, and it may be preferable to stay with the usual unless there is a strong argument for change. The world becomes easier to interpret if as much as possible is held constant. […] Change is easier to manage if we know it is coming. The better prepared someone is for a change, generally the easier it is to cope. For people with ASD, it helps if the preparation can be as concrete as possible.”

“The paradoxical nature of ASD is demonstrated again in attention span. The person will be absolutely absorbed, blocking out the rest of the world, when he is engrossed in something of particular interest; but at other times his attention span can be low. Most people will recognize the experience of being called away to answer a phone call, or speaking to a visitor and completely forgetting that they were in the middle of doing something. This distractibility is a common experience for those with ASD. […] I often think that ASD is the source of the stereotype of the ‘absent-minded professor’.”

A personal remark on these topics is perhaps in order here, and I add it because it is my impression that mass media portrails of individuals with these sorts of traits are generally if anything favourably inclined; in the sense that distractibility, forgetfulness and these sorts of traits are in those contexts in general traits you smile about and which are mildly funny. My impression is that the first word that springs to mind in these contexts is ‘amusing’, or something along those lines, not ‘annoying’. The downsides are usually to some extent neglected. However I know from Real Life experience that things like forgetfulness and distractability can be really annoying. Forgetting the key to your flat and locking yourself out of your flat (multiple times); forgetting to bring home your laptop from the university and having to go back and get it while worrying about whether or not it’s been stolen in the meantime (it fortunately wasn’t); getting caught up in an interesting exchange on the internet causing you to you forget that you turned on the stove an hour ago (or was it two hours ago? Time flies when you’re engaged in stuff that interests you…), so now you’ll have to spend another hour trying to clean the pot and separate the charred chunks of vegetables and the metal; getting a burn while taking something out of the oven because you were thinking about something else and didn’t pay sufficient attention to the task at hand – these things border from annoying to dangerous, as also noted in the book: “Depending on what we were doing, finding that we have left something in the middle of it can be anything from mildly annoying (left the kitchen half cleaned) to very distressing (left the pan on the hob and burnt the house down).” Similar observations might be made in the context of ‘clumsiness’ (not a diagnostic trait, but apparently often observed) and combinations of these traits. The sorts of things people often find amusing when they happen to, say, cartoon characters are a lot less funny when they happen to you personally, especially if you are having difficulties finding ways to address the issues and other people are impacted by them as well. Problems like these may cause amusement among others, but I know from both personal experience and the experiences of a good friend of mine that they may also cause profound exasperation among the people around you.

“Difficulty with communication is a core problem for those with autism spectrum disorder (ASD). Some people have little or no speech, some have an extensive vocabulary, some make grammatical mistakes, some have a wide use of language – but all people with ASD have problems with communication. These problems are extremely complex, leading to much misunderstanding, confusion and stress. The more sophisticated the person’s language is the greater the problem may be. Ros Blackburn, a highly intelligent British woman with ASD who gives many talks on the subject, highlights that a person’s ability can also be their greatest disability. As a verbal, intellectually able woman, she finds that people do not appreciate the support that she needs in everyday and social situations. The power to have a seemingly normal conversation can cause many troubles for a person with ASD by giving a false impression of their comprehension. […] Care should be taken not to give too much information at one time. People with ASD generally process language slowly and have difficulty handling a lot of verbal input. […] People with ASD work through matters slowly, and speed of discussion is problematic. […] So time needs to be offered to assimilate information before a response is expected. […] For most people with ASD, it is easier to talk if there are fewer people in the group. In a large meeting there is too much to take in, and few silences in which to process what has been said. […] They almost always prefer one to one conversation to group discussion, and small intimate gatherings to parties.”

“We all make blunders in relationships. We misjudge what is acceptable in a situation, mistake another person’s intention or misinterpret someone’s meaning. We then feel upset, isolated and embarrassed. People with ASD are more prone to doing this sort of thing than most – and they do experience the same unpleasant aftermath. […] Coping well is a double-edged sword; the better a person manages, the more likely he is to be judged harshly when he does make a mistake. […]  Some people with ASD are able to think their way through social situations. They teach themselves or have been taught to interpret non-verbal signals. They can use cognition to remember that the other person may feel differently to them, and to compute what their perception and emotions may be. This is a slow, cumbersome method compared to the automatic, rapid assimilation that those without ASD make. Even those who compensate well appear slow, stilted, awkward, and are liable to make significant mistakes.”

“Neurotypical people (NTs) are as lacking in empathy towards people with ASD as vice versa.” This is in my opinion a bold claim and I’m not sure it’s true, but I think she does have a point here. I think it’s likely that NTs often judge people with ASD based on the standards of NTs; standards which may well be impossible for the person with ASD to ever meet, regardless of the amount of effort the individual puts into meeting those standards. She however argues later on in the coverage that: “Most people are not unkind, but are unthinking or, because of lack of knowledge about disability, make incorrect assumptions.” This seems plausible.

“The rigidity of AS thinking and the tendency to obsess means that a worry can escalate and dominate a person’s life. […] As a basic rule of thumb, regular, familiar routines are better stress busters than a novel idea. A holiday, for example, is more likely to add to stress than relieve it.” (This sounds very familiar, and I’ll keep this quote in mind…)

“Many people with ASD remain more susceptible to parental influence than the majority of their peers. […] All people with ASD, including the highly intelligent, are susceptible to being led by others and it is very easy for the person offering support, either knowingly or unwittingly, to lead the person down a route, which is not the course he wants to follow.”

“Social inabilities create problems for people with autism spectrum disorder (ASD) in establishing peer relationships and so naturally accessing the support that evolves between members of groups, such as work colleagues, fellow students or regulars in the pub. Asking for assistance appropriately will be challenging for people with ASD. […] adults often only appear on the services ‘radar’ when they reach crisis point. Forty-nine per cent of adults with ASD are still living with their parents. […] Only 6 per cent of adults with ASD are in full-time employment [no sources provided, US]”

“It is not always possible to tell from meeting a person or even from having regular contact with him that he has autism spectrum disorder (ASD). Individuals therefore face the decision as to whether or not to disclose that they have the disorder. […] Generally disclosure is on a sliding scale. Most people tell close family; whilst it would probably be inappropriate to tell a casual stranger. Some will disclose to professionals, but prefer to keep the information from social contacts. […] There are no easy answers as to who and when to tell. Disclosure to professionals in formal situations appears advisable so that all are aware of the condition and any differences are accepted and planned for. Informal social situations are more fluid and difficult to read.”

“NAS statistics show that only six per cent of people with autism spectrum disorder (ASD) (12% of those with Asperger Syndrome (AS)) in the UK are in full-time employment. This compares with 49 per cent of people with general disabilities who are employed. […] Given the talents which many with ASD have, this is a great loss to the workforce. […] Traits common to ASD, such as conscientiousness, attention to detail, perseverance and loyalty, are great assets to an employer. […] People with ASD tend to be loyal, to stick to routines and dislike change. […] The characteristics of the disorder mean that the individual may not make a good impression at interview. Social skills will not be a forté. […] The employer needs to be aware of any ASD traits the person displays, such as lack of eye contact. Questions may be prepared with support so that they elicit the information needed, but are specific, factual and clear. Broad questions, such as, ‘Tell me about yourself ’, will leave the interviewee floundering. […] Interviews are not always the most appropriate way of assessing candidates, especially not those with ASD.”

The author does not address in the book the specific problems and tradeoffs related to the question of whether or not it’s optimal to disclose an autism spectrum disorder to a potential employer, but rather seems to take it for granted that the interviewee should always disclose, preferably beforehand. I’ve given this a lot of thought, and I’m really not convinced this is always the right approach.

May 17, 2015 Posted by | autism, Books, Medicine, Personal, Psychology | Leave a comment

Adolescents and Adults with Autism Spectrum Disorders (2)

I read the rest of the book, but I didn’t particularly like the last part either – I gave the book one star on goodreads. A couple of the last chapters were sort of okay, but they were not good enough for me to change my mind about the book in general.

“Whether the child who is suspected as being on the autism spectrum is “high” or “low” functioning, it is important to ascertain a sense of their global functioning particularly in the area of ADLs [activities of daily living]. Many professionals erroneously assume a “highfunctioning” individual with perhaps, Asperger syndrome functions in the community at an age appropriate level. Professionals are often beguiled by “Aspies” vocabularies and intelligence. They may think it is unnecessary to conduct an assessment of the person’s adaptive functioning because his or her IQ is in the normal to superior range. However, because of impairments in social communication, executive functioning, and the ability to read facial expressions and non-literal communication, individuals with Asperger syndrome can have extreme difficulty functioning on a daily basis. […] many are diagnosed in adulthood […]. For a community-based sample in Canada, 48 % of individuals with “high-functioning autism” and AS were not diagnosed until they were 21 years or older (Stoddart et al., 2013). […] In higher-functioning individuals with average to above-average IQs, there is often a “cloak of competence” […] or an assumption of competence when it comes to […] basic life skills. Adults who are highly accomplished in their work may have basic problems with organization at home, or for tasks which are of less interest […] outcome is variable, as some individuals with very high IQ face significant challenges in adulthood. […] Depressed mood may be particularly common in high functioning adults, who have insight into their social and adaptive difficulties, and who may desire to make changes but have limited success in doing so”

“higher functioning individuals who have a considerable vocabulary may still have a [speech] disability. Individuals with Asperger syndrome for example have an impressive vocabulary even at a young age, but they have impairments in the semantics and pragmatics of speech. They may also have issues with prosody that need to be assessed and addressed.”

“Understanding which variables predict adult outcomes in ASD is a crucial goal for the field, but we know little about what variables predict different outcomes. […] Longitudinal studies of ASD from childhood to adulthood have consistently yielded only two useful prognostic factors for adult outcome in ASD. A childhood IQ score in the near-average or average ranges (i.e., ≥70) and communicative phrase speech before 6 appear necessary but insufficient for a person to access a moderate level of independence in adulthood […] Individuals having these childhood characteristics have widely varying adult outcomes, so exhibiting these characteristics in childhood is no guarantee that a person will achieve adult independence. The predictive utility of other childhood variables has been examined. Findings regarding severity ratings of childhood ASD symptoms have been mixed”

“Almost all studies that have examined developmental trajectories for individuals with ASDs show that these individuals exhibit reductions in autistic symptoms over time […] Symptoms of ASD tend to diminish both in severity and number. The most improvement has usually been recorded for participants with IQ scores in the normal range and the least severe symptom presentations at their initial evaluation […] Published reports also indicate that there are subgroups of individuals with ASD who experience marked change in the course of their development at some point, either as deterioration or dramatic improvement. […] This phenomenon was […] noted in a Japanese sample of 201 young adults, although marked improvement was also described […]. Roughly one-third of this sample experienced a marked deterioration in behavior, most often occurring after age 10. The change occurred after age 20 in six cases. Declines were characterized by specific skill regressions or by increases in hyperactivity, aggression, destructiveness, obsessive behavior, or stereotyped behaviors. Notable improvements in the developmental course occurred in 43 % of the sample […] Improvements occurred between the ages of 10 and 15 years for most participants. No predictable antecedents to changes in the developmental course have been noted in previous studies. […] Significant improvements in verbal communication abilities have been reported on the ADI-R, although findings related to nonverbal communication have been mixed.”

“While not a core diagnostic domain at this time, difficulties processing sensory information are common in people with ASD and considered an associated feature […]. In a study of sensory processing difficulties in 18 adults with ASD and normal-range IQ scores aged 18–65, Crane, Goddard, and Pring (2009) found that, compared to matched controls, adults with ASD reported more experiences with low registration (i.e., responding slowly or not noticing sensory stimuli), sensitivity to sensory input, and avoiding sensations. All but one person reported extreme scores in at least one area.”

“Outcome classifications usually include five nodes ranging from Very Poor (i.e., the person cannot function independently in any way) to Very Good (i.e., achieving great independence; having friends and a job). There is considerable variation in outcomes for samples studied, but in general outcome for approximately 60 % of individuals with ASD is considered Fair, Poor, or Very Poor […]  Most outcome studies indicate that few adults with ASD develop significant relationships
outside of their families of origin. […] It is [however] likely that the majority of adults with ASD who also have normal range intellectual abilities have not been diagnosed, and many of these individuals may have married or developed other close relationships outside of their families of origin. […] In terms of outcome studies to date, very few adults with ASD have been reported to have successful, long-term romantic relationships […]. Some outcome studies indicate that no participants or only one participant has been involved in a romantic relationship […]. One-third to half of adults in outcome studies have friendships outside of their families […]. Almost 75 % of family members reporting on the sample described by Eaves and Ho (2008) indicated that they enjoyed good to excellent relationships with their relative with ASD. Similar results have been found in other studies of adults with A[S]D […]. Females have reportedly experienced greater success with peer relationships than males […]. Between 10 and 30 % of adults in recent studies (Eaves & Ho, 2008; Engstrom et al., 2003; Farley et al., 2009) had experience in a romantic relationship. […] Roughly one-third of adults with normal-range IQ scores in outcome studies are employed, inclusive of regular, full-time work, part-time or volunteer work, supported employment, and sheltered employment. […] Roughly 40 % of participants in outcome studies have been prescribed medications for psychiatric conditions or to control behavior”

“Ganz (2007) estimated the societal costs of ASD across the lifespan, calculating a total per capita societal cost for an individual with ASD at over $3 million. The most expensive period was early childhood, at which time many children are undergoing diagnostic studies, receiving medical treatments, and participating in intensive intervention programs. Costs for young adults (ages 23 through 27) were estimated to be $404,260 (in 2003 dollars). Ganz calculated direct medical, direct nonmedical, and indirect costs. Direct medical costs are expenses incurred in the course of medical care, and these tended to be lower for adults than other age groups. Direct nonmedical costs include adult support services and employment services, as examples. This life period often involves much trial-and-error while families attempt to identify services that will result in a good fit with their son or daughter. Direct nonmedical costs were higher in this age group than any other, estimated at $27,539 over this 5-year period. Indirect costs mainly comprise lost productivity costs, as when family members must leave work or reduce hours in order to support their family member. These costs are also the highest for this age group because adult children may remain dependent on their parents, but are also technically old enough to enter the workforce. Therefore, lost productivity costs are calculated for parents as well as the young adult, a phenomenon unique to this life period. Societal costs diminish as adults with ASD age, so that someone aged 48 through 52 incurs less than half the cost of someone aged 23 through 27.”

“Virtually nothing is known about ASDs in late life. Questions at the forefront about this period are related to brain changes, the transfer of care from parents to other family members or human service agencies as parents become unable to care for their adult children through illness or death, and the adequacy of existing services to care for this population. There are many questions about the nature of changes in the brain in adults ASD as they approach old age. We do not know whether or not they experience memory problems at a similar rate to adults in general population, nor whether they may experience earlier onset of dementia and increased rates of dementia”

Chapter 15 was actually sort of okay and deals with a community survey conducted in Britain where some researchers tried to figure out how many autistics are out there, undiagnosed, in the community, and how well those individuals are actually doing compared to other people. Instead of going into the details of that chapter I’ll just point you to the original paper they describe in the text. The paper behind chapter 16, which I’ll talk a little bit about below, is available here.

“While evidence is accumulating regarding the benefits of psychosocial interventions for adults with ASD, there have been no systematic reviews or meta-analyses conducted to summarize the cumulative evidence base for these approaches. Therefore, we conducted a systematic review to examine the evidence base of psychosocial interventions for adults with ASD […] An extensive literature search was conducted in order to locate published studies documenting interventions for adults with ASD […] These searches revealed 1,217 published reports. Additionally, references of relevant studies were examined for additional studies to be included in this research. […] From these abstract searches, studies were then examined and included in this review if they (1) were conducted using a single case study, noncontrolled trial, non-randomized controlled trial, or RCT design that reported pretest and post-test data, (2) reported quantitative findings, (3) included participants ages 18 and older, and (4) included participants with ASD. In total, 13 studies assessing psychosocial interventions for adults with ASD were found. […] The included studies were diverse in their methodologies and represented numerous categories of interventions. A total of five were single case studies, four were RCTs, three were non-randomized controlled trials, and one was an uncontrolled pre–post trial. Six studies evaluated the efficacy of social cognition training, five studies evaluated the efficacy of applied behavior analysis (ABA) techniques, and two studies evaluated the efficacy of other types of communitybased interventions. […] All of the included ABA studies were single case studies. […] All ABA studies reported positive benefits of treatment, although the maintenance of this benefit varied between studies. Effect size was not reported for the ABA studies, as findings were based on a single subject. […] As a whole, the studies identified had modest sample sizes, with the greatest including 71 participants and over three-quarters of studies having less than 20 participants.”

“there are significant limitations to the current evidence base. While we conducted an extensive search of the literature available on psychosocial interventions for adults with ASD since 1950, only 13 studies were found. Due to the small number of studies, we were unable to conduct a meta-analysis of the adult ASD literature. As a consequence, clear estimates of effect size for different types of psychosocial interventions are not available. Effect sizes should also be interpreted with caution, especially for studies with small sample sizes, which comprised the majority of studies. The incongruent nature of outcome measures used in some of the included studies also indicate that the reader should take caution before generalizing the results of included studies. For instance, García-Villamisar & Hughes (2007) used cognitive functioning outcomes, such as the Stockings of Cambridge and Big Circle/Little Circle tasks, to measure the effectiveness of a supported employment program but did not report outcome data on the number of adults with ASD who were employed as a result of the program.”

October 4, 2014 Posted by | autism, Books, Psychology | Leave a comment

Adolescents and Adults with Autism Spectrum Disorders (1?)

I’ve been reading and I have at this point almost finished Sexual Selection in Primates: New and Comparative Perspectives, an awesome book which I’ll certainly give five stars and most likely add to my goodreads favourites, yet now I find myself covering this borderline-lousy book instead. The reason why I’m doing that is simple: Kappeler & van Schaik’s book (the awesome one) is an oldfashioned paper book, which makes it a lot more work to blog than this one.

I’m not impressed with Volkmar et al.’s coverage, and I’m at the moment considering whether I should even finish it – thus the question mark in the parenthesis; if I don’t read any more of it, I’ll certainly not post another post about the book later. It is a rare thing for me to do, to stop reading a book once I’ve decided that it’s worth reading; I’ll often quite quickly get a sense of whether a book is worth reading or not, and I rarely give up on a book once I’m past the first 100 pages. I did not at any point think this book was awesome and I’ve throughout the book so far been somewhere between one and two stars on goodreads, but it’s one of very few books dealing with the topic covered so it’s not like there are a lot of alternatives out there, and this gave the authors some leeway they would not otherwise have had. The most recent chapter I read, on Pharmacotherapy of Behavioral Symptoms and Psychiatric Comorbidities in Adolescents and Adults with Autism Spectrum Disorders, however was very close to pushing me over the limit. Here are some sample quotes from that chapter:

“A case report described a 25-year-old male with Asperger’s disorder who was diagnosed with bipolar I disorder with psychotic features after exhibiting a period of hyperactive, irritable, and assaultive behavior, reduced need for sleep, and grandiose, persecutory delusions (Arora, Praharaj, Sarkhel, & Sinha, 2011). Symptoms of mania improved on a combination of clozapine 200 mg/day and haloperidol 20 mg/ day”

“Clozapine is an atypical antipsychotic that is limited in use due to an increased risk of agranulocytosis and potential to lower the seizure threshold. A case series in three individuals with autism, aged 15-, 17-, and 27-years-old, highlighted successful treatment with clozapine for the management of recurrent aggression toward self and others (Chen, Bedair, McKay, Bowers, & Mazure, 2001; Gobbi & Pulvirenti, 2001; Lambrey et al., 2010).”

“A case series examined this glutamate antagonist in the treatment of three individuals with autism and MR, aged 15–20 years (Wink, Erickson, Stigler, & McDougle, 2011). Dosages ranged from 100 to 200 mg/day. There were reductions in interfering repetitive behaviors in all three subjects.”

“There is one double-blind, placebo-controlled, crossover study of clonidine involving adolescents and adults in the treatment of “hyperarousal behaviors” associated with autism (Fankhauser, Karumanchi, German, Yates, & Karumanchi, 1992). […] This study examined nine males with autism, aged 5–33 years (mean age, 13 years) […] Transdermal clonidine resulted in significant clinical improvement on the Clinical Global Impression-Improvement (CGI-I) scale.”

“The majority of published research on the pharmacological treatment of comorbid psychiatric disorders is limited to case reports and a few open-label studies. […] Although case reports have found some pharmacologic treatment beneficial for psychiatric comorbidities in individuals with ASDs, double-blind, placebo-controlled studies are needed”

One of the authors of that chapter had multiple conflicts of interest which were disclosed towards the end of the chapter, as he’s apparently received research funds from six different pharmaceutical companies. In the chapter they cover studies involving three individuals and even single case stories like the one above (it’s far from the only one). I’m not sure those two observations are unrelated. I think if all you have is a case series involving 3 individuals it’s probably not necessary to include that stuff in a book like this; that sort of information is close to worthless (single case stories certainly are. That’s what we in other areas call ‘anecdotes’). Once you know that some of the randomized controlled trials in this field involve only 9 subjects, you also start becoming a lot less impressed with those. They make conclusions in that chapter which I would not have made based on the evidence they present. A really serious omission is also that polypharmacy is not even mentioned in the chapter, despite a substantial number of people taking more than one type of drug and despite the fact that we basically have no clue how this affects them (see Lubetsky et al. for more on this). This omission is so much more striking as the polypharmacy issue is actually brought up, or at least mentioned, already in the introductory chapter of the book, where the authors note that “Of those receiving medications [in one study of 480 Canadians from Ontario with ASD], over 80 % received more than one medication.”

One reason why I’ve been reading on is that occasionally there are some interesting data, but another reason is that this book probably provides a good illustration of how people working in this field thinks. They, incidentally much like the authors in Lubetsky et al., seem to think there’s no budget constraint – they worry about it to the extent that they’re not given money to spend, but they seem to have no notion of the existence of questions like: ‘but isn’t it simply insane to be spending that kind of money on this?’ They have  a lot of ideas about how you could improve outcomes, and I’m sure some of those ideas if implemented might improve outcomes – whether it would be ‘worth it’ is however a completely different question, a question they do not ask.

I have added some observations from the first half of the book below.

“adolescence and adulthood in ASD [autism spectrum disorder] remain rather poorly understood. Much of the research and clinical work has centered on young children and those of primary school age […] We now understand that ASD is an early-emerging, usually lifelong neurodevelopmental disorder that significantly impact social, communicative, cognitive, and adaptive skills and has a strong genetic basis […]. There is now an extensive literature of peer-reviewed, scientific papers focused on ASD, and multiple studies on adult outcome have been published (for a review, see Howlin, 2013). As Howlin notes, however, these focus almost exclusively on outcome in young adulthood and information on older individuals is limited […], with almost no research focused on aging […]. Of the studies focused on outcome, most have studied individuals with classic ASD, or “Kanner’s” autism and “outcome” is essentially confined largely to early adulthood. […] heterogeneity in both the disorder itself and in service delivery, render it a complicated landscape for the study of intervention and outcome […]. Changes in nomenclature and diagnostic taxonomy have also complicated interpretation of research over the years and of identification of older individuals on the autism spectrum […] The relationship between severity of early symptoms of autism and ultimate outcome remains unclear, with at least a few studies suggesting that the severity of social skills impairment is the most significant outcome predictor […]. This and many other questions regarding changes in outcome remain to be discovered. Past young adulthood the literature becomes quite sparse. In one review of autism, research studies conducted between 2000 and 2010 only 23 (of an estimated 11,000) were focused on adult services […] Despite the important limitations of the research literature, it does appear that on balance outcome has, and is continuing, to improve.”

“The data available suggest that most individuals as adults live with parents/family and that a minority is employed. […] Even for the most able adults, however, limitations in social interaction, in adaptive/daily life skills, and occupational status [are] striking, with nearly 60 % of cases [in the previously mentioned Canadian study] continuing to live with their families. About one third of [that] sample had had romantic relationships and in a few cases had been married (sometimes with offspring). Most of the sample reported major limitations in social connections (with many having one or fewer social encounters outside their living situation each month). […] Outcome studies have shown a wide range of variation in the number of individuals with autism who have left home to live independently, in a group home, or some supported living arrangement. A number of studies have shown that the majority of young adults continue to live at home with their parents. […] Even when adults with autism live outside the family, their families especially their mothers have extensive contact and involvement in their care. Kraus et al. (2005) reported that 50% of families visited their adult with autism at least weekly and an equal number of adults came weekly to visit at their mother’s home. […] This need for continued parental support crosses the entire spectrum of individuals with autism.”

“Recent reviews of outcomes for individuals with ASD through the National Longitudinal Transition Study-2 (NTLS2) have indicated that, as a group, individuals with ASD have low rates of employment, independent living, and lifelong friendships (Newman, Wagner, Cameto, & Knokey, 2009). This longitudinal study followed 11,000 transition-aged students with disabilities from 2001 to 2009. The age range of youth and young adults included in this study were between 13 and 26. This sample included 922 students with autism spectrum disorders. Outcomes recorded for this sample included the following findings […]: • 32 % of this sample attended post-secondary education of one type or another • Only 6 % achieved competitive employment • 21 % had no job or post-secondary education experiences at all • 80 % continued to live with their parents • 40 % reported having no friends”

“The relationship between typically developing siblings has been extensively studied; however, very few studies have been conducted in order to investigate the interactions and quality of relationship between siblings when one has autism. For a typically developing sibling, the influence of having a brother or sister with autism is associated with higher rates of behavioral and emotional concerns […] and fewer prosocial behaviors towards their sibling with autism in some studies […] Within the literature, higher levels of education of the typically developing sibling as well as living at a distance from their sibling with autism have negative consequences for their perceptions of the sibling bond”

“There is limited research on the spouses of individuals with ASD. With the increasing knowledge and identification of high functioning men and women, there is a growing awareness that a portion of adults with ASD do enter into long-term relationships with others […]. However, there is limited empirical data about the nature of these relationships. […] adolescents and adults with ASD have far fewer sexual experiences than their typically developing peers […] Nichols and Byers (2008) found that participants who were older and had fewer ASD symptoms reported better sexual functioning. Specifically, individuals with fewer ASD symptoms reported greater sexual satisfaction, sexual self-esteem, assertiveness, arousability, and desire. They also reported fewer sexual problems and less anxiety surrounding sexual issues. As such, a sizable population of individuals with ASD is capable of having a satisfying sex life.”

“An impairment in social interaction is a core symptom of ASD […] and can impact social communication, friendship-making, dating, relationship-building, as well as sexuality. These deficiencies can lead to a decrease in social relationships […], an increase in loneliness […], an increase in social isolation, and poor quality friendships […]. Furthermore, co-morbid diagnoses of other mental disorders are common among this population. Individuals with Asperger’s are 5.7 times more likely to develop symptoms of depression in comparison to the typically developing population (McHale, Dariotis, & Kauh, 2003; Stewart et al., 2006). The literature suggests that most individuals with ASDs show a desire for relationships, but experience loneliness because their difficulties with social skills often interfere with friendship formation […] in a study of “high-functioning” individuals with autism, more than 56% had never experienced a sexual relationship and only 25% had dated […] as a whole, studies repeatedly show that although individuals with ASD desire intimate relationships, few actually have them. […] [People] with ASD often lack the social skills knowledge and competence to appropriately pursue and engage in successful romantic relationships […]. For example, individuals with ASD have been known to naively behave in an intrusive manner with potential romantic partners, which may even be perceived as stalking behavior”

“Despite the pervasiveness of social deficits commonly experienced among individuals with ASD, social skills are comparatively much less studied than other aspects of ASD and research examining social skills interventions for adolescents and adults with ASD are especially rare. In a best evidence synthesis of 66 studies of social skills interventions for individuals with ASD published between 2001 and 2008, only three studies contained adolescent or adult participants […] Social deficits are typically a major source of impairment for individuals with ASD, regardless of cognitive or language ability […]. However, the considerable heterogeneity in the level of cognitive functioning and language ability among individuals with ASD may affect the presentation of social deficits. For example, Bauminger, Shulman, and Agam (2003) found that higher-functioning adolescents initiate social interaction with peers more frequently than do their lower-functioning peers; yet, their interactions are often awkward and sometimes even intrusive or offensive. […] high functioning adolescents may be no less affected by social deficits than those with cognitive limitations; rather, their heightened self-awareness and false appearance of being less impaired may actually increase the severity of their social limitations and motivation, perhaps increasing the likelihood of peer rejection and neglect. Consequences of poor social skills often manifest in the form of peer rejection, peer victimization, poor social support, and isolation. Consequently, individuals with ASD generally report higher levels of loneliness and poorer quality of friendships”

“adults with ASD often present with more depression and anxiety than their adolescent counterparts […]. Interestingly, higher-functioning adults with greater intelligence and less autistic symptomatology tend to experience more depression, anxiety, social isolation, withdrawal, and peer victimization […] than lower-functioning individuals. This may be due in part to greater social expectations often placed on higher-functioning adults occurring as a result of placement in less protective and more inclusive settings. With higher-functioning adults with ASD often giving the appearance of seeming more “odd” than disabled by their peers, these individuals may be more susceptible to peer rejection, and consequently greater negative socio-emotional outcomes like depression and anxiety. Furthermore, greater self-awareness about peer rejection and “differentness” more likely found in higher-functioning adults with ASD may also contribute to greater depression and anxiety”

“While social skills training has been utilized for decades and is not a particularly unique or novel treatment for individuals with ASD, the research literature suggests that these approaches have not been tremendously effective in improving the social functioning of individuals on the autism spectrum […] While social skills training has increasingly become a popular method for helping individuals with ASD adapt to their social environment […], a review of the research literature suggests there are very few evidence-based social skills interventions for adolescents and adults with ASD […]. With emphasis on early intervention, most social skills treatment studies have targeted younger children on the autism spectrum, with few clinical research trials focusing on adolescents or adults with ASD. Among the limited number of social skills intervention studies conducted with this population, most have not been formally tested in terms of their efficacy in improving social competence or the development of close friendships, nor do they examine the maintenance of treatment gains months or years after the intervention has ended. […] the literature on social skills training for youth with ASD has been far from encouraging. In a review of the social skills treatment literature, White et al. (2007) identified 14 studies that used group-based social skills training for children and adolescents with ASD. Among these studies, only one used a randomized control group design […] None of these studies examined the maintenance or trajectory of improvement in social competency over time […] Even fewer studies have focused on social skills treatment for adults with ASD. To date, only three published studies appear to have tested the effectiveness of a social skills intervention for adults with ASD […] Only 4 of the 14 studies White et al. (2007) included in their review employed a RCT with a control group. In a similar review of social skills training interventions for children and adolescents with ASD, Rao et al. (2008) found that 9 out of 10 reviewed studies did not use a RCT as their research design. […] Regrettably, most social skills intervention studies are limited in their ability to generalize research findings to other settings and other populations of adolescents and adults with ASD. Two of the biggest offenders to generalization relate to sample size and participant characteristics. Most social skills training intervention studies for adolescents and adults with ASD have small sample sizes […] single-case experimental designs with approximately three or four participants appear to be the most common research design employed within social skills training studies”

September 27, 2014 Posted by | autism, Books, Medicine, Psychology | Leave a comment

Habituation: Theories, Characteristics and Biological Mechanisms

As already mentioned, this book was one of the books I read last week. I gave it two stars on goodreads.

The book did not have a goodreads profile, so I had to add one. When books don’t have goodreads profiles and/or I’m unable to find an amazon rating, I usually end up (cautiously) assuming that the book probably has not been read by, well, let’s use the words ‘a lot of people’. As you may be able to tell from the goodreads book description which I included in the profile at the link above, it’s a book which deals with some slightly obscure stuff: “Topics include the important roles for matrix metalloproteinases and cell adhesion molecules in long-term potentiation (LTP)” and “a mathematical description of habituation and recovery of the head-shake response in rats“. The description at the link is a quote from the book – it’s the first paragraph of the preface. Some of the stuff in here is fairly technical and really quite difficult to blog also on account of being somewhat difficult to summarize – for these reasons there was some stuff in the book which I decided against covering here despite it being interesting, including most of the first chapter. The stuff I decided to exclude includes the stuff about ‘important roles for matrix metalloproteinases and cell adhesion molecules’ but I also decided to exclude the coverage of the drug addiction stuff in that chapter, however for a different reason; I’ve dealt with this kind of stuff before, and Clark et al.’s coverage go into much more detail than does this book.

Below I have added some observations from the book and a few remarks of my own.

“Nonassociative learning is considered to be the simplest form of learning and includes the phenomena of habituation, dishabituation, and sensitization. Of these phenomena, habituation is the most frequently studied and refers to a decrease in responding, as related to frequency, magnitude, or intensity to a stimulus repeatedly presented, or presented for a prolonged period of time […] Habituation has been documented across many species and response systems ranging from the gill-withdrawal reflex in Aplysia [sea slugs] […] and tap withdrawal or chemotaxic response in the nematode Caenorhabditis elegans [a ~1 mm long roundworm] […], to acoustic startle response in rats and mice […], schedules of reinforcement in operant conditioning […] and feeding in humans (Myers and Epstein, 2002).”

“From the viewpoint of neuroscience, tinnitus has been defined as (i) the perception of a sound in the ear in the absence of external stimulation […]; (ii) an ongoing conscious perception of a sound in the absence of any external sound source […]; (iii) the conscious perception of a sound that is not generated by any source outside the body […]; (iv) a phantom auditory perception or the perception of abnormal activity not induced by any combination of external sounds […]. As documented almost thirty years ago by Coles (1984), approximately 14-18 per cent of the population included in an epidemiological study in Great Britain reported tinnitus. Findings from a community survey conducted in Gothenburg, Sweden showed that 14.2 per cent suffer “always” or “often”, and it has been estimated that 1-2 per cent perceive tinnitus as a plague all day or as a threat towards quality of life […]. More recent epidemiological surveys from China (Xu et al. 2011) and Egypt (Khedr et al. 2010) demonstrate that tinnitus can be a significant problem for the inhabitants in the eastern part of the world as well. Overall prevalence of tinnitus in a population of 6333 inhabitants in a province (Jiangsu) in China was 12.4 per cent and standardized rates for China was calculated to be 11.4 per cent. […] In a survey in Assiut, Egypt including 4848 inhabitants prevalence rate of tinnitus was 5.17 per cent. […] Along with these results, earlier epidemiological studies also disclosed that a large proportion of individuals do not seek help for having tinnitus, so a clinically relevant question to rise was, and still is, why some patients are plagued by tinnitus, while others seem to be able to cope. In one of the first larger tinnitus populations studies Meikle et al. (1983) investigated the relationship between tinnitus loudness obtained by a loudness balance procedure and tinnitus severity ratings in 1800 patients attending a tinnitus clinic. No significant correlation was found between tinnitus loudness and severity. Neither was the severity ratings associated to type, quality and the pitch of tinnitus.”

I thought prevalence was significantly lower than that, but I must admit that i did not have good reasons for assuming this. Tinnitus seems to be yet another one of those sneaky health problems which are both reasonably hard to observe when other people suffer from them (you can’t tell if someone has tinnitus or not unless the individual in question tells you that he or she does) and actually quite common. The chapter has a lot of stuff, much of which are critical remarks towards current therapeutic approaches and the interpretive frameworks (there are two relevant models, a ‘psychological model’ and a ‘neurophysiological model’) on which they are based. The reason why this condition is included in the book is that a habituation process often occurs in people who are affected by this condition – most people with tinnitus adjust to some extent to the condition. However: “To date, habituation to tinnitus remains an unexplained process [and] it is not legitimate to state that tolerance to tinnitus is a natural process”. Habituation is the common outcome, but sometimes it fails and they don’t really seem to have a good explanatory model of what goes wrong when it does. It should be noted that a few of the people who do not habituate to tinnitus end up killing themselves – so figuring out more about this stuff is most certainly not unimportant to some of the people who are affected. Some of the details which are clear at this point is that the habituation process relates to a lot of stuff besides what’s going on in the ear, and that some treatment-relevant patient heterogeneities do not seem to be taken into account in the current treatment modalities on offer (or for that matter in the theoretical models on which the treatment modalities are based). Incidentally it may be a mistake to think of the neurological research into these things as only being relevant to the organism’s ‘response to tinnitus’, as such processes may well also be implicated in the pathophysiology more broadly defined – at least this is how I interpret some of the findings. For example they point out in chapter 5 of the book that: “recent auditory neuroscience research has suggested that an imbalance of excitatory and inhibitory neural interactions within the auditory cortex could lead to the perception of tinnitus”.

“The model of orientation and habituation that will be discussed is derived from the work of Sokolov (1975). Sokolov postulated that production of an orienting response is dependent on incongruity between incoming stimulus and existing neural templates that are created by previously stored memory traces of environmental stimuli. The neural template or model encodes all aspects of the stimulus including duration, interstimulus interval and the relationship between several stimuli across time. If there is a mismatch between the new stimuli and the neuronal template, sensitization to the stimulus occurs and a response will be generated. If the new stimulus matches the neural template, habituation occurs (i.e., decrease in responding to repeated presentations of the same stimuli). […] If a stimulus differs in any way from the original stimulus presented (i.e. higher or lower pitch), the orienting response will reappear to a previously habituated stimulus because of the change. Sokolov termed the reappearance of the orienting response dishabituation. […] It is argued that Sokolov’s model captures the organism’s ability to modulate internal memory traces and compare these traces to external stimuli to determine the importance or irrelevance of stimuli in the environment. However, it does not directly address the activation or suppression of the motor system in orienting to novelty or inhibiting responding to irrelevant stimuli. Orienting must involve two interactive channels of information processing: automatic and conscious. These two channels must be integrated by feedforward and feedback interconnections that involve many functional brain systems. The widespread involvement of different brain regions is further implicated by the research finding of cingulotomy patients. […] damage to the cingulate can produce attentional impairments.”

“It is proposed that orientation and habituation occur through the modulation of both internal and external states. The modulation of information occurs in three separate levels as follows: (1) memory comparator level, (2) value-appraisal level, and (3) behavioral-response/decision-making level […]. All of these levels are processing the information simultaneously through synchronized connections of neural circuits between the functional areas involved. The memory comparator level is composed of the hippocampus.
The value-appraisal system is composed of the amygdala, orbitofrontal cortex and peripheral nervous system. The peripheral nervous system is important in controlling the organism’s arousal system. One division expends energy (sympathetic) and the other division conserves energy (parasympathetic). The behavioral-response/decision-making level is composed of the cerebellum, basal ganglia, premotor, motor cortex and anterior cingulate. It is proposed that the cerebellum is the key structure involved in linking the temporal properties of signals especially with regard to the basal ganglia and the anterior cingulate.
It is also proposed that the anterior cingulate plays an important role in coordinating internal and external influences on stimuli processing and response monitoring. The anterior cingulate receives initial information as well as feedback; it determines priorities in selecting which stimuli to attend and respond to. There is considerable agreement in the literature indicating that the role of the anterior cingulate cortex is to assist in bringing together the influences of internal and external stimuli with behavioral goals and plans for activation […] Evidence from animal, clinical and neuroimaging studies indicates that the anterior cingulate cortex is involved in directing attention and action by modulating cognitive and affective states […] The anterior cingulate cortex may be involved in processing competing inputs and inhibiting competing actions (Pardo, Pardo, Janer and Raichle, 1990) or directing attentional responses when there are multiple or competing inputs and action (Pardo, Fox, and Raichle, 1991). In this sense the anterior cingulate has several roles but its most important role may be in optimizing behavioral stability. […] The proposed three levels of modulation are highly dependent on the diffuse and broadly distributed neuronal circuits in the brain.”

“The NE [neurotransmitter norepinephrine] system serves a very specific function; it maintains the basic level of excitability, arousal, and attentiveness.
The NE system plays an important modulatory role in learning, memory, and retrieval. Norepinephrine also appears to be more inhibitory than excitatory. Over activity can lead to hypervigilance and anxiety and under activity can lead to depression. Norepinephrine is known to be involved in behavioral arousal due to the affects of certain drugs. Amphetamine and cocaine act on NE and are both potent brain stimulants. Several studies have provided evidence that effects of stimulus significance and stimulus repetition are a function of noradrenergic control originating in the pontine nucleus LC.” [Yes, I noticed the spelling errors and they were part of the reason why I included this paragraph in the coverage – to illustrate this aspect of the coverage. Sloppiness like this is part of why I gave the book two stars. The chapter from which this quote is taken is not that terrible, but chapter five – written by a couple of Italian researchers – is quite bad.]

“Neurons do not operate in isolation; each neuron affects the activation of another neuron. The connections between neurons can be excitatory (the firing of one neuron makes the other more likely to send its own signal), or inhibitory (the firing of one neuron makes the other less likely to send its own signal). The excitatory or inhibitory effects neurons have on each other are an important construct in the present model. Connections between neurons (or neural circuits) are determined by the strength between them, or in other words, the degree to which the activation of one affects the activation of another. Too little strength between the neurons or an imbalance in neural synchronization can cause a disruption in processing. The efficient processing of neural circuits can also become weakened when other circuits interfere with their functioning. Of additional importance is the fact that neural connections can be made stronger or weaker through learning. […] In the proposed model sensory information from the environment is received in the amplifying system (thalamus, reticular activating system), which is responsible for arousal, amplification and relay of signals. Information is then forwarded to the memory comparator system (hippocampus), the value-appraisal system (amygdala, orbitofrontal cortex), and behavioral-response/decision-making system (cerebellum, basal ganglia, anterior cingulate, and motor areas). In processing information for decisional action, the organism will habituate if there is a memory trace in the hippocampus (event memory with affect) and cerebellum (motor response memories) from prior experience. If the organism habituates to irrelevant information, the RAS [reticular activating system] is tonically inhibited by the hippocampus and cerebellum. If there are no memory traces, the organism is aroused to process the sensory signal for its affective/motivational salience by the amygdala and orbitofrontal cortex. The cerebellum initiates a motor response (“what is it”) at which time the basal ganglia and anterior cingulate become activated for further processing. After the initial stimulus is processed in these regions, information is sent back to sensory areas thus creating a feedback loop. As information in the environment is being refined and updated, sensory areas continue to receive new input and the feedback from the monitored response as well. In this sense, a dynamic and complex process that is cyclical in nature is proposed. Stimulus perception, selection, and response initiation is being fed forward and fed back at each stage in processing and the influences of these processes are sorted for priority by the anterior cingulate cortex. Thus orientation and habituation is a continuous process that enables the organism the flexibility to adapt to changes in the internal and external environment.”

“Habituation is not only a gating mechanism that is extremely critical in attentional processes but it also dampens arousal (e.g., reticular activating system) and motor behavior […]. Thus habituation is a process that also involves inhibitory control. Stated differently, the same mechanisms of habituation would be recruited to sustain willed attention to an activity (e.g., habituating to environmental distractors in order to read a book) and to automatically capture attention if the demands of the environment change (e.g., sound of a fire alarm that pulls our attention from reading). Overall, research findings indicate that habituation processes are impaired in ADHD […], ASD [autism spectrum disorder] […] and TBI [traumatic brain injury] […]. Moreover, the deficits in habituation facilitate the explanation of the characteristic symptoms of these disorders […] At the present time however, the underlying neural correlates of habituation can only be speculated”.

There isn’t a lot of research supporting the ‘research findings’ part above (the ASD part is only supported by one “unpublished manuscript”…), but this seems to be the kind of stuff some people are looking into these days.

“Habituation is a reduction in responsiveness to repeated or prolonged stimulation; that allows nervous system filters to identify biologically less relevant input in the flow of sensory information, and in turn devote more attention and processing energy toward more relevant or dynamic stimuli. This form of non-associative learning enables an animal to perceptually deemphasize persistent o[r] static stimuli in favour of novel of changing stimuli. Habituation has been described experimentally in multiple sensory modalities within various invertebrate and vertebrate species including sea slugs, fruit flies, nematodes, birds and mammals [1]. The observed decrements in responding in reflexive behavior are not mediated by motor fatigue or adaptation at the level of sensory receptors. The distinction between fatigue and habituation is commonly made by demonstrating that the response decrement is specific to the repeated stimulus [2], [3]. Change in stimulation, such as introduction of an intense stimulus, allows a return of responsiveness (dishabituation) or heightened responsiveness (sensitization). […] Habituation reflects an intact central nervous system (CNS) with normal functioning [10]; habituation can be detected before birth [11–13] and can be used to evaluate the maturation of the fetal CNS [14].”

“Habituation in olfaction allows the olfactory system to maintain equilibrium with the odorant concentrations in the ambient environment, yet respond appropriately to the appearance of novel odors or changes in odorant concentration. Olfactory habituation can be induced by multiple paradigms that differ in timescale and are thought to be mediated by distinct mechanisms within different regions of the olfactory system […] Some studies have revealed that the odors are processed differently in relation to their valence: chemosensory evoked potentials towards pleasant and unpleasant odors change with repeated presentation [47], in particular unpleasant odor produced earlier response, as for fulfil their warning function about potential threats [48].”

“The traditional definition of motion sickness has been the onset of vomiting or nausea experienced by the land, air, sea, or space traveler that results in impaired function. Motion sickness can be induced […] by either physical motion or stimuli that result in perceived motion […] Manifestations of motion sickness may include visual and postural instability, pallor, diaphoresis, excess salivation, sweating, dizziness, malaise, headaches , anxiety, hyperventilation, nausea and vomiting. All of them are attributable to activation of the autonomic system in response to vestibular stimuli [50], as if motion sickness itself could have evolved from a system designed to protect from potential ingestion of neurotoxins, by inducing vomiting when unexpected central nervous system inputs are detected (the “toxin detector” hypothesis)[51]. Less popular alternatives to the toxin detector hypothesis propose that motion sickness could be the result of aberrant activation of vestibular-cardiovascular reflexes [52], or that motion sickness is a unfortunate consequence of the physical proximity of the motion detector (vestibular) and vomiting circuitry in the brainstem [53]. […] a conflict between visual and vestibular information regarding spatial orientation has been identified as the primary causal factor for motion sickness [56]. […] The principles of habituation have been applied with varying success to reduce or prevent motion sickness in pilots and astronauts [57–59]. Habituation programs pioneered by military are effective but time consuming. […] Research on habituation training has focused on the use of visual or vestibular stimuli, and results support the concept that habituation is stimuli-specific [62]: tolerance to car travel may have no effect on susceptibility to seasickness.”

August 27, 2014 Posted by | autism, Biology, Books, Medicine, Neurology, Psychology | Leave a comment

Autism Spectrum Disorder (II)

I finished the book. Here’s what I wrote on goodreads:

“Parts of the coverage was complete crap and/or dealt with stuff that was not remotely interesting to me, but other parts were actually really good – which makes the book sort of difficult to rate. In the end I decided to settle on a two star rating, even though I consider some of the recommendations made in the book to be far from ‘okay’.”

One of those recommendations is to give narcotics to young children with abnormal brains who don’t behave the way the parents would like them to, even though it’s clear that such approaches only deal with symptoms and do nothing to address actual underlying causes (see below: I haven’t quoted extensively from this part of the book, but you should note that I draw different conclusions than do the authors – as I incidentally do in other areas as well..). Ritalin, Adderall, etc.; subjecting young children with brains which are still developing to these types of pharmacological interventions just make my skin crawl, especially as I consider it more or less beyond doubt that part of what is going on here is simply medicalization of normal behaviours.

I have added some observations from the last half of the book below.

“Over the years there have been many [behavioural] interventions developed for young children with ASD [autism spectrum disorder]. Thus far, research has not demonstrated that any particular intervention approach is better than the others. […] The amount of empirical support for different treatment approaches varies significantly. However, in general, more empirical support is needed for all approaches, and studies comparing the efficacy and effectiveness of different approaches are sorely lacking. […] many community-based programs may offer eclectic approaches combining elements of various types of interventions within a single program. Although we are beginning to understand better the types of approaches that seem to be successful for young children with autism and their families, we really have no way of knowing the extent to which eclectic, community-based approaches are successful.”

“Impairment in social communication is one of the diagnostic criteria for ASD; therefore, communication is universally affected in individuals with ASD. Social communication includes many nonverbal aspects such as eye gaze and facial expression. […] The degree of affectedness of spoken language can vary widely in individuals with ASD. Sixty to 70% of individuals with ASD are low-verbal or nonverbal [“30% of individuals with autism develop fluent spoken language”], with substantial difficulty with the understanding of spoken language and the ability to use it for functional communication (Fombonne, 2005). However, most children with ASD develop some spoken language skills [“50% of individuals with autism develop some usable spoken language”]. In a study of a large sample of nine-year-olds with ASD, fewer than 15% were classified as nonverbal (defined as using fewer than five words per day) […]. Children with ASD generally have large amounts of immediate or delayed echolalia in which they immediately imitate what someone else says or repetitively use language they have heard from sources such as television, movies, books, or videogames. […] Echolalia is thought to result because children with ASD have an abnormally large “attentional window” for language, resulting in learning larger “chunks” of language. Multiple words are treated as if they were a single word. […] Even high-functioning individuals with ASD may have difficulty with understanding the social use of language because they interpret words literally and have difficulty making inferences. Highly verbal individual with ASD may monopolize the conversation by going on and on about a topic that is interesting to them and failing to give their communication partner a turn to speak. Language proficiency or verbal ability is consistently associated with positive outcomes in social and adaptive functioning for children and adults with ASD.”

“The employment outcomes for individuals with high-functioning autism and Asperger’s disorder are reported to be generally much lower than would have been expected on the basis of their intellectual functioning (Howlin, 2004)” [Here is one relevant quote from the book which I found after a brief skim: “despite having IQ scores well within the normal range (and sometimes reaching quite high academic levels) the majority of individuals in both the Asperger and high-functioning autism groups studied by Howlin (2003) had no close friends, remained highly dependent on their families for support and had low employment status” – unfortunately no specific data was included in that section. This article has some more general numbers dealing with all individuals on the autism-spectrum – one relevant quote: “The unemployment rate for autistic people seems to be about 66%, according to data from 2009, compared to about 9% for the general population. Some estimates, like Bell’s, are even higher: 80-85% unemployment.”]

“People with ASD require predictability, consistency, and structure”

“Most individuals with ASD are diagnosed in early childhood or by school-age. Some young adults are evaluated for symptoms of high-functioning autism or Asperger’s disorder that have not been identified earlier.” [It seems my experience is not unique… No, I did not think it was…]

“Some common characteristics seen in persons with ASD that may lead to difficulty coping include:
• Challenges in interpreting nonverbal language
• Rigid adherence to rules
• Poor eye-gaze or avoidance of eye contact
• Few facial expressions and trouble understanding the facial expressions of others
• Poor judge of personal space — may stand too close to other students
• Trouble controlling their emotions and anxieties
• Difficulty understanding another person’s perspective or how their own behavior affects others
• Very literal understanding of speech; difficulty in picking up on nuances
• Unusually intense or restricted interests in things (maps, dates, coins, numbers/statistics, train schedules)
• Unusual repetitive behavior, verbal as well as nonverbal (hand flapping, rocking)
• Unusual sensitivity to sensations […]
• Difficulty with transitions, need for sameness
• Possible aggressive, disruptive, or self-injurious behavior […]

Situations that often increase anxiety for persons with Asperger’s disorder and lead to difficulty coping include:
• When conversation involves multiple speakers
• Rapid shifting of topics
• Latency of response
• Difficulty in seeking clarification
• Lack of confidence
• Overabundance of irrelevant information”

“Research supporting the use of CBT [cognitive behavioural therapy] in ASD is limited […] At this stage, it remains difficult to make strong conclusions regarding the efficacy of CBT in people with ASD”

“There are currently three well-accepted theories of social development in ASD. Each will be briefly described below.
Theory of Mind deficit
Definition: Difficulty with both awareness and understanding of another individual’s perspective. This was later referred to as “mind blindness.” Research has shown that most typical children learn this skill by age four, while children with ASD learn this much later, between the ages of nine and 14 years.

The social implications of Theory of Mind deficits (Cumine et al., 1998)
• Difficulty predicting the behavior of others, leading to the avoidance of anxiety-producing situations
• Difficulty reading the intentions of others and understanding motives behind their behavior
• Difficulty explaining their own behavior
• Difficulty understanding emotions, their own and those of others, leading to the appearance of lack of empathy
• Difficulty understanding how their behavior affects how others think or feel, leading to an apparent/perceived lack of conscience or motivation to please others
• Difficulty taking into account what other people know or can be expected to know, leading to the appearance of disorganized cognitive processing
• Inability to read and react to the listener’s level of interest in what is being said
• Inability to anticipate what others might think of one’s actions
• Inability to deceive or understand deception
• Poor sharing of attention
• Lack of understanding of social interactions that enable the initiation and maintenance of social relationships […]

Central Coherence deficit
Definition: Difficulty drawing multiple sources of social and environmental information together, causing problems with understanding the larger contextual picture.

The social implications of Central Coherence deficits (Cumine, et al., 1998)
• Idiosyncratic focus of attention
• Imposition of the individual’s own perspective onto others’ experiences
• A preference for the known
• Inattentiveness to new tasks
• Difficulty choosing and prioritizing
• Difficulty organizing themselves, materials, and experiences
• Difficulty seeing social connections, thus causing problems with generalizing skills and knowledge
• Lack of compliance with directives that they do not understand […]

Executive Functioning deficits
Definition: Difficulty with the following executive functioning skills:
• Planning
• Self monitoring
• The ability to inhibit various social responses
• The ability to express behavioral flexibility
• Processing and expressing information in an organized and fluid manner

The social implications of Executive Functioning deficits (Ozonoff, 1995)
Causes difficulties with the following:
• Perceiving others’ emotions
• Imitation of social behaviors
• Pretend play, which is essential to early learning
• Planning, organizing, and prioritizing
• Starting and stopping activities, behaviors, and thoughts”

“Just as there is a spectrum of autism, there is also a range of social motivation. Some individuals are extremely interested in engaging with their peers, but struggle to appropriately initiate or maintain social connectedness. Others with ASD have very little social motivation. These individuals often report extreme anxiety when engaging with people for a variety of reasons. For example, it may be difficult to predict how the people around them will behave and, therefore, individuals on the spectrum may chose to avoid all anticipated anxiety-provoking social environments. […] Many people assume that a lack of social initiation and reciprocal communication indicates that individuals with ASD lack the desire to engage in social interaction. On the contrary, many individuals with ASD lack the skills to be successful socially, yet they desire to be a part of social relationships”

“A recent meta-analysis of 55 single-subject research studies revealed that “social skills programs for children with autism are largely ineffective” (Bellini, 2007).”

“no medication has yet been identified that is capable of treating the core features of ASD […] However, various medications have been used to treat behavioral symptoms in ASD […] Antidepressant medications have been used in the treatment of specific psychiatric comorbid disorders in individuals with ASD. They have also been used to target selected symptoms in ASD such as repetitive preoccupations, preseverative behaviors, and social anxiety. […] The Interactive Autism Network (IAN) reported in 2009 that, out of 5,174 children diagnosed with ASD, 12.2 % of them [were] taking antidepressant medication. […] [The] reports [on antidepressants] have been anecdotal, small case studies, and small designed studies. Investigation has been limited by small sample size, broad age range, and being uncontrolled. The [single] large double-blind, placebo-controlled study of citalopram in 149 children with ASD […] found that there was no significant improvement on multiple measures. […] Antiepileptic medications are typically used for treatment of seizures, which may occur in approximately one third of children with ASD […] Mood-stabilizing antiepileptic drugs (AEDs) have also been used to treat mood instability, agitation and aggression in ASD. Despite the availability of more than a handful of double-blind trials (most of which failed to support the use of AEDs), surveys of psychopharmacological use among children and adults with ASD suggest fairly frequent use. […] It is not uncommon for individuals with ASD to be prescribed more than one psychotropic medication. For example, in the 2005 ASD psychoactive medication survey conducted by Aman and colleagues, 9.8 % of the sample were identified as taking two different drugs; 7.7 % were taking three drugs […] To date, we are unaware of any randomized controlled trials involving the use of polypharmacy in ASD.”

[I also talked about these aspects in the previous post, but I think they’re more clear about the details in the last part of the coverage than they were in the parts on this stuff I covered earlier, so I’ll include these observations as well:] “Considering that deficits in communication and social behaviors are inseparable and more accurately considered as a single set of symptoms with contextual and environmental specificities, the DSM-IV-TR’s three domains (communication deficits, social deficits, stereotypic interests and behaviors) become two in DSM-5: (a) social/communication deficits, and (b) fixated interests and repetitive behaviors. The newly proposed diagnosis for ASD requires that both criteria to be completely fulfilled. In addition, the current clinical and research consensus appears to be that Asperger’s disorder is part of ASD. Research currently reflects that Asperger’s disorder is not substantially different from other forms of “high-functioning” autism with good formal language skills and good (at least verbal) IQ.”

July 26, 2014 Posted by | autism, Books, Language, Medicine, Pharmacology, Psychology | Leave a comment

Autism Spectrum Disorder (I)

Assburger(smbc)

I recently realized that I had actually never read a textbook like this on this topic. I did get some reading materials back when I got diagnosed so it’s not like I’ve never read anything about the stuff (and there was a lot of verbal information back then as well), but as mentioned I haven’t read a text on the topic. It was actually due to the old reading materials in question that I ended up deciding to read this book; I was looking for some other stuff the other day and I ended up perusing some of these materials (which I hadn’t seen in years), and I figured I should probably go read a book on the topic. Now I am.

The book is sort of okay. There are various complaints one might make, the most important one of which in the context of me reading the book is perhaps that children with autism-spectrum disorders grow up and become adults, and adults prefer to read chapters about adult stuff, not stuff about e.g. how to teach the preschooler with the diagnosis social skills. I’ve read roughly half the book at this point, and there’s not in my opinion been enough stuff about the adult setting at this point. Another complaint is that I as usual am somewhat mistrustful when guys like these talk about the conclusions to be drawn from some types of empirical evidence; the coverage has in my opinion been of a decidedly mixed quality in terms of the stuff dealing with behavioural interventions, in the sense that they on the one hand at one point reasonably frankly acknowledge that the evidence is sparse and of poor quality, and on the other hand later on seem to become very excited about a longitudinal study and start drawing big conclusions from that single study – which would be sort of fine, I like longitudinal studies, if not for the fact that the study was based on 6 (!) individuals. Similar things happen elsewhere in that part of the coverage – potential power issues are never mentioned in the book, at least they have not been so far – you find yourself reading about a ‘seminal’ study on 19 individuals, and then you move on to their comments about how there have been several other studies supporting those findings, including a study looking closer at 9 of the individuals involved in the original study. Sometimes it’s hard to know what to think, especially in the situations where the only people evaluating the interventions are the people who came up with them in the first place – this doesn’t seem like a particularly smart way to conduct business, though in some parts of psychology it seems to be more or less standard practice.

The stuff on behavioural interventions has in my opinion been some of the weakest stuff in the book so far, which is why I have not talked about this stuff in my coverage below. Some of the proposed interventions are incredibly expensive, and there’s probably a good reason why such things are usually not covered by public health care systems, however the authors do not really seem to consider economic aspects to be all that important, except to the extent that economic factors unfortunately restrict access to all these nice things we could do for these children; they’re aware that parents may not be able to afford the treatment options which are recommended at this point by people who would benefit from these treatment options being more widely used, but they don’t seem to be aware of the existence of things like cost-effectiveness analyses. It’s one thing to argue that there may be developmental gains to be achieved by early childhood interventions (I’ve previously done work in educational economics and I can tell you that it is a common finding in this literature that you can improve outcomes by throwing lots of money and attention after young children – a finding which should perhaps not be super surprising..), it’s quite another thing to argue that the specific interventions comtemplated are cost-effective. To be fair, cost-effectiveness is incredibly hard to evaluate when you’re contemplating evaluating interventions which may have effects lasting basically the rest of the life of the individual and the intervention is supposed to take place during the first years of a child’s life, but in my opinion you sort of need to at least pretend to try to address this aspect somehow; if you don’t, you’re quite likely to end up in a situation where it seems as if you’re acting as if there’s no (societal) budget constraint, and the authors of this book seem to me to move very close to this position at various points in the coverage.

I knew very little (nothing?) about autism-spectrum disorders before I got the diagnosis – I got diagnosed very late, in my adulthood. It’s sort of funny how you can miss important stuff like this without even knowing, and in a way it relates to a point which came up in my recent post on ethics, specifically the point that ‘bad’ people tend to think they are ‘good’ people, or at least no worse than average. How much do you really know about how good other people are at, say, interpreting nonverbal social signals? Would withdrawal from social interaction make the comparison easier or harder? If you don’t really engage in the normal patterns of non-verbal information exchanges, e.g. eye contact exchanges, during social situations, how are you to know that important information is contained in such exchanges? Individuals seem to make assumptions about these things to a large extent based on what they know themselves (about themselves?), and if you have limitations in these areas it may be difficult to figure out that this is the case; another apt analogy might be children who need glasses early on in their lives – we screen for vision impairment in young children in part because young children don’t know, and may never on their own ever realize, that the world is not supposed to be blurry, and that you’re actually supposed to be able to see all the letters written down on the blackboard.

I thought I should make one thing clear before moving on to the main text, a point particularly relevant considering the comic which I decided to start out with; which is that incompetence should not be equated with/interpreted as malicious intent. It seems to me that many people conceive of people with autism-spectrum disorders as inconsiderate jerks who don’t have a clue – I’ve seen quite smart people state relatively similar things in the past. I dislike the ‘jerk’-model because I try to be thoughtful and considerate when interacting with others, and when these people think that way I feel that they’re devaluing the work I put into this stuff. One important problem which is sort of hard to figure out how to deal with is that I’m well aware that the more thoughtful and considerate I am (…or is it: ‘try to be?’) during social encounters, the more taxing the social interactions may become, and taxing social interactions lead to social isolation and withdrawal. Coming up with a good equilibrium level of effort is not an easy task, and I think one needs to address aspects like these before making strong judgments about things like the jerkishness of specific behaviours. In a way people with social anxiety have similar concerns which other people also cannot observe (in this case it would be excessive amounts of thinking during social situations about whether they are doing stuff right now that may mean that they’ll get rejected by others, which then leads to oversensitivity to clues of rejection, leading to social avoidance because of perceived rejection). Of course people with autism-spectrum disorders may be anxious as well, as also mentioned in the coverage below. The level of self-awareness varies a lot in people with autism-spectrum disorders, but people with relatively high levels of self-awareness may certainly face some constraints and tradeoffs which are not immediately obvious to the outsider and which may actually be assumed by neurotypicals to be absent, given the diagnosis.

The textbook answered one question I’d been thinking about a few times without ever worrying enough about it to actually seek out an answer, which is the question of what the recent diagnostic changes might mean, given that I have a diagnosis which by now has been ‘retired’. It turns out that I was diagnosed with what in the textbook are considered to be the ‘gold-standard tools’, which means that this remark related to the recent diagnostic changes that have taken place seems to answer the question: “The DSM 5 noted that “Individuals with a well-established DSM-IV diagnosis of” “Asperger’s disorder” “should be given the diagnosis of autism spectrum disorder””. I’m not going to ‘ask’ for a ‘new’ diagnosis (/a ‘translation’ of my diagnosis) (and quite aside from what other people like to call this stuff, I like the word ‘eccentric’ a lot better than the word ‘autistic’…), but it’s nice to know which recommendations are being made in this area. Some of the quotes below also relate a bit to these aspects.

I’ve added some quotes from the book below.

“Autism is a developmental neurobiological disorder characterized by severe and pervasive impairments in reciprocal social interaction skills and communication skills (verbal and nonverbal), and by restricted, repetitive, and stereotyped behavior, interests, and activities. […] Autism and autistic stem from the Greek word autos, meaning “self.” The term autism originally referred to a basic disturbance, an extreme withdrawal of oneself from social life, or aloneness. […] The critical point in the scientific history of autism was in 1943, when Leo Kanner published Autistic Disturbances of Affective Conduct, a groundbreaking paper that described the symptoms of 11 children presenting similar behaviors that had not been previously recognized. […] Based on Kanner’s terminology, autism was considered for years a psychosis, and child psychiatrists were using “childhood schizophrenia” and “child psychosis” in autism as “interchangeable diagnoses.” […] A parallel line of inquiry to that of Kanner and Eisenberg is represented by the work of Hans Asperger.”

“In Autism and Pervasive Developmental Disorders, Fred Volkmar and Catherine Lord (2004) distinguished important points of differentiation and similarities between Kanner’s and Asperger’s descriptions. […] In concluding their comparison of Kanner’s and Asperger’s descriptions, Volkmar and Lord pondered whether, despite the relevant differences, it was “scientifically and clinically helpful to classify individuals with these traits into separate categories of autism or Asperger’s disorder, or whether it would be better to treat them as parts of a greater continuum.” The utility of the “greater continuum” has led to the category of autism spectrum disorder to be proposed for DSM-5. […] As a result of [various findings] and the lack of reliability in the community in making distinctions among the ASDs [Autism-Spectrum Disorders] [for example: “Variations in clinical severity among ASD cases are not valid indices of differences in pathophysiology or etiology”], the Fifth Edition of the Diagnostic and Statistical Manual (DSM-5) proposes to collapse all of these clinical syndromes into a single diagnosis of “autism spectrum disorder.” Although this revision is appropriate for community diagnosis, and thus the allocation of clinical and support services, research studies will continue to rely on research diagnostic instruments like the Autism Diagnostic Interview (ADI) and the Autism Diagnostic Observation Schedule (ADOS) [these were both part of my work-up, US] to make categorical distinctions between “autism and not autism” and “autism and autism spectrum disorder” (which includes Asperger’s disorder and PDDNOS [Pervasive Developmental Disorder Not Otherwise Specified]). These distinctions have played a vital role in advancing our understanding of the behavioral and neural profile of ASD over the past two decades”

“Recent studies and reports from the Centers for Disease Control […] have shown an increase in the prevalence of children diagnosed with an ASD to one in 110 […] The reported increase is thought to be attributable to several factors. First, there have been changes in diagnostic practices […] Second, there is greater public awareness of ASD and more case-finding […] Finally, there has been a tendency to diagnose many children with intellectual disability as PDD. […] no evidence currently exists to support any association between ASD and a specific environmental exposure. […] Numerous studies have failed to demonstrate a causal relationship between immunizations, particularly thimerosal-containing vaccines, and ASD […] The CDC (2009) reports the median age for a diagnosis of ASD to be between 4.5 and 5.5 years. […] the ASD diagnosis is four times more common for boys than in girls.”

“The essential features of Asperger’s disorder are severe and sustained impairment in social interaction (criterion A); and the development of restricted, repetitive patterns of behavior, interests, and activities (criterion B); which must cause clinically significant impairment in functioning (criterion C). There are no clinically significant delays in language (criterion D) or cognitive development (criterion E).”

“ASD (excluding Asperger’s disorder) has early language and communication impairment. […] almost two thirds of individuals with ASD also have ID [intellectual disability] […] 15%–20 % of cases of ASD are now linked to genetic or
chromosomal abnormalities […] Fragile X Syndrome (FXS) [is] the most common identifiable cause of ASD and the most common inheritable cause of ID. […] Thirty percent of individuals with FXS demonstrate characteristics of ASD.” [In some other conditions penetrance is even higher – examples that could be mentioned are 15q duplication and Timothy Syndrome, but prevalence is lower in these cases and especially in the latter case some might argue that the autism is the least of that child’s problems..]

Challenging behaviors [in individuals with ASD] may reflect pain that is not communicated verbally […] Challenging behaviors may [also] reflect the child’s difficulty with communication, changes, new places, new situations, new experiences, new sounds, new smells, and new people” [I wonder if you can spot a pattern here in terms of what these children (/people) don’t like? I think an important distinction here is to be made between curiosity and the desire to try out new things. I’m often, hesitant, about trying out new things, yet I’m also quite curious about a lot of things. Be careful which categories you apply here and how they may impact your thinking… In a related vein:] “Insistence on sameness and difficulty with change are common symptoms of an ASD. These behaviors should not typically be considered a behavior done to exert control over others.”

“Psychiatric comorbidity is now acknowledged as quite common in ASD [and] psychiatric comorbidity increases the level of impairment […] There is a handful of questionnaires [aiming at spotting psychiatric comorbidities] that have been developed specifically for use in developmentally disordered or ASD populations. […] none of the measures has the level of research support possessed by questionnaires used in other branches of psychiatry. The vast majority of these instruments have just one study behind their development, or have been studied only by the developer of the instrument. […] one of the main challenges in diagnosing psychiatric disorders in individuals with ASD is the possibility of different presenting symptoms and difficulty in differentiating impairment related to the underlying ASD from impairment due to a separate condition. […] While we do not want to miss true comorbid diagnoses, over-diagnosing comorbidity can be equally harmful. […] Mood disorders, such as depression and bipolar disorder, in ASD have recently begun to receive a great deal of attention […] there are many potential psychosocial stressors that could be possible triggers. For example, higher-functioning individuals who are aware of their deficits and badly desire friends, but lack success in this area, are at particular risk. […] Although there is little research on emotion regulation in ASD, there is clear evidence that emotion regulation is highly variable and often problematic in this population, regardless of psychiatric comorbidity […] Therefore, particularly for mood disorders, it is imperative to consider baseline functioning and not over-diagnose mood disorders when the concern may be more temperamental in nature.”

“Anxiety is considered by some to be the most common comorbid psychiatric concern in ASD […]. The DSM-IV-TR notes that individuals with ASD might have unusual fear reactions, and it is also not uncommon for there to be a general tendency toward anxiety for many individuals with ASD. […] There are many aspects of having an ASD that may lead to this increased risk for anxiety, to the degree that some consider anxiety and the social impairment in ASD to have a bidirectional relationship […] An increase in self-awareness is considered a risk factor for higher anxiety; therefore, anxiety is typically thought of as more common among individuals with ASD who have higher intellectual abilities, and older children, adolescents, and adults.”

“autism may be conceptualized as a disorder of complex information processing resulting from disordered development of the connectivity of cortical systems (e.g., failure of cortical systems specialization) […] approximately 15%–20% of infants with an older sibling diagnosed with autism will ultimately be diagnosable with ASD by three to four years of age. […] [Findings from longitudinal sibling studies] do not support the view that autism is primarily a social-communicative disorder and instead suggest that autism disrupts multiple aspects of development rather simultaneously. […] When both elementary and higher-order abilities in many domains are assessed, it becomes evident that deficits exist in several domains not considered to be integral parts of the autism syndrome, including aspects of the sensory-perceptual, motor, and memory domains. Furthermore, there are enhanced skills and impaired abilities within the same domains as deficits (e.g., memory, language, abstraction). […] Causal explanations for ASD must account for the comprehensive pattern of both deficits and intact aspects of the disorder both within and across multiple domains. […] There is no single primary deficit or triad of deficits, brain regions, or neural systems causing autism. […] Rather, autism broadly affects many abilities at the same time and systematically from its earliest presentation and throughout life. […] This pattern [can] be characterized overall as reflecting a disorder of complex or integrative information processing, which results from altered development of cerebral cortical connectivity in ASD. […] Just as the infant sibling studies have clearly demonstrated, studies of children and adults with autism have also demonstrated a broad but selective profile of deficits and intact or enhanced abilities that all reflect a relationship to information-processing demands. […] it is likely that genes affecting signaling pathways that regulate neuronal organization are strongly implicated in the etiology of autism.”

“ASD is now conceptualized as a developmental neurobiological disorder affecting elaboration of the forebrain circuitry that underlies the abilities most unique to human beings. […] Wiring the brain requires that neurons proliferate, acquire the correct identities, migrate to the appropriate locations, extend axons, and make guidance decisions with a high degree of spatial and temporal fidelity. Converging evidence indicates that more than one of these processes may be altered in various combinations to produce the heterogeneous phenotypes observed in ASD. […] Studies examining head circumference (HC) and brain volume (BV) in individuals with ASD have demonstrated altered brain growth trajectories across the lifespan. […]
• Up to 70 % of infants with ASD exhibit abnormally accelerated brain growth in the first year of life. Approximately 20% to 25% of infants in this subset actually meet formal criteria for macrocephaly (i.e., HC of 2.0 standard deviations above the mean) in the first year.
• BV is significantly larger by two to four years of life, and some children meet criteria for megalencephaly (i.e., BV 2.5 S.D. above mean).
• The first two years of life are usually a period of rapid brain growth in infants as neurons undergo significant postnatal growth in cell size and elaboration (actually overproduction) of axons, synapses, and dendrites. It is possible that this process is exaggerated somehow in at least a subset of ASD.
• Whatever the neurobiological basis, abnormal growth rates in ASD tend to decline significantly after the initial acceleration, causing an apparent “normalization” of BV by adolescence or early adulthood. […]
At the time of maximal brain growth in very early childhood, cerebral gray matter (GM) and white matter (WM) are both increased […] The frontal cortical GM and WM show the most enlargement, followed by the temporal lobe GM and WM and the parietal GM.”

“Thus far, [fMRI and fcMRI] studies have identified underconnectivity with the frontal cortex as a specific characteristic of the altered connectivity in autism, and this characteristic is present across the same wide range of domains of complex information processing that are affected in the disorder, including social, language, executive, and motor processes. […] measures of functional connectivity between specific areas have been shown to reliably predict the degree of impairment in specific domains among those diagnosed with autism. For instance, individuals with poorer social functioning measured by the ADI-R show lower functional connectivity between frontal and parietal cortices. These findings gave rise to the underconnectivity theory in autism, which now has sufficient support that it is accepted as a central feature of the pathophysiology of autism […] Results from these studies are consistent with the notion that autism is a disorder of distributed neural systems (e.g., the connections between structures rather than the structures themselves). […] Diffusion-weighted imaging measures the direction and speed of microscopic water movement in the brain, allowing inferences about the microstructure of the tissue that constrains such movement. These studies have consistently found reduced structural integrity of white matter in adults with ASD, indicating reduced anatomical connectivity […] like measures of functional connectivity, measures of anatomical connectivity derived from diffusion imaging have been shown to reliably predict symptom severity among individuals with autism.”

“In thinking about the genetic basis of autism, it is important to contrast syndromic (or complex) and non-syndromic (or idiopathic/essential) ASD. […] Syndromic ASD includes identifiable autism syndromes with known genetic causes, such as tuberous sclerosis complex, Fragile- X syndrome, Rett syndrome, and Smith-Magenis syndrome.
• Syndromic ASD is associated with a relatively higher propensity for dysmorphic features (including anatomical brain abnormalities), intellectual disability (ID), seizures, and female sex (sex ratios are almost equal).
• Syndromic ASD is also associated with a higher frequency of chromosomal abnormalities in general, many of which have been identified […]. However, it is not yet clear for many of these syndromes which features are typical of autism and which are unique.
Non-syndromic ASD is also called idiopathic autism and consists of cases with and without identifiable micro-deletions or duplications to the DNA. […] individuals with idiopathic ASD are more likely to be male, with sex ratios approximately 1:4 (F:M) but approaching 1:7 in milder cases.”

“Overall, approximately 10 % of children being evaluated for ASD are found to have an identified medical condition with a known genetic lesion such as Fragile X or tuberous sclerosis. An additional 10 % or more have an identifiable chromosomal structural abnormality or copy number variation associated with ASD. […] Recent genome-wide scans using microarray technology have demonstrated a substantial role for small chromosomal deletions or duplications (i.e., copy number variation or CNV) in the etiology of ASD. […] There is [however still] considerable debate concerning the genetic architecture underlying […] the majority of idiopathic autism. Arguments can be made for either the effects of single, but rare Mendelian causes (for which documented CNVs are presumably the tip of the iceberg) or the interaction of numerous common, but low-risk alleles. Genetic linkage and association studies have been traditionally employed to address the latter model, but have failed to consistently identify susceptibility loci.” [An important point I should perhaps make before finishing this post is that if incidence/prevalence of a condition is increasing fast in a population, which seems to be the case here, such an increase is in general considered to be unlikely to only be the result of genetic changes at the population level – that type of pattern is usually indicative of environmental factors playing an important role. It may well be that the ‘average cause’ is different from the ‘marginal cause’, and that it may be a good idea to be careful in terms of which tools to use to explain base rates and growth rates. It might be argued that increased assortative mating among nerds in Silicon Valley has increased incidence locally (I’m sure this might be argued as I’m quite sure I’ve seen this exact argument before…) and I’m not saying this may not be the case, but if close to one percent of the American population get diagnosed, what goes on in Silicon Valley probably isn’t super relevant one way or the other – only roughly 1% of the population live in that area altogether. Even if you were to argue that a similar process is going on everywhere else in the country, it sort of strains belief that ‘something else’ is not going on as well].

July 25, 2014 Posted by | autism, Books, Epidemiology, Genetics, Medicine, Neurology, Personal, Psychology | Leave a comment

Stuff

I thought I should update the blog even though these days I don’t do a lot of blogging-worthy stuff.

i. A blog I recently discovered: Empirical Zeal. There’s some interesting posts there, for example I liked this one on the state of Indian rural education (though the findings reported are not exactly worthy of celebration).

ii. The acquisition of language by children. From the introduction:

“Imagine that you are faced with the following challenge. You must discover the internal structure of a system that contains tens of thousands of units, all generated from a small set of materials. These units, in turn, can be assembled into an infinite number of combinations. Although only a subset of those combinations is correct, the subset itself is for all practical purposes infinite. Somehow you must converge on the structure of this system to use it to communicate. And you are a very young child.

This system is human language. The units are words, the materials are the small set of sounds from which they are constructed, and the combinations are the sentences into which they can be assembled. Given the complexity of this system, it seems improbable that mere children could discover its underlying structure and use it to communicate. Yet most do so with eagerness and ease, all within the first few years of life.”

It’s actually pretty wild, once you start thinking about it.

iii. The Null Ritual – What You Always Wanted to Know About Significance Testing but Were Afraid to Ask (via Gwern? I no longer remember how I found this.). An excerpt from the article:

“Question 1: What Does a Significant Result Mean?

What a simple question! Who would not know the answer? After all, psychology students spend months sitting through statistics courses, learning about null hypothesis tests (significance tests) and their featured product, the p-value. Just to be sure, consider the following problem (Haller & Krauss, 2002; Oakes, 1986):

Suppose you have a treatment that you suspect may alter performance on a certain task. You compare the means of your control and experimental groups (say, 20 subjects in each sample). Furthermore, suppose you use a simple independent means t-test and your result is signifi cant (t = 2.7, df = 18, p = .01). Please mark each of the statements below as “true” or “false.” False means that the statement does not follow logically from the above premises. Also note that several or none of the statements may be correct.

(1) You have absolutely disproved the null hypothesis (i.e., there is no difference between the population means). ® True False ®
(2) You have found the probability of the null hypothesis being true. ® True False ®
(3) You have absolutely proved your experimental hypothesis (that there is a difference between the population means). ® True False ®
(4) You can deduce the probability of the experimental hypothesis being true. ® True False ®
(5) You know, if you decide to reject the null hypothesis, the probability that you are making the wrong decision. ® True False ®
(6) You have a reliable experimental finding in the sense that if, hypothetically, the experiment were repeated a great number of
times, you would obtain a significant result on 99% of occasions. ® True False ®

Which statements are true? If you want to avoid the I-knew-it-all-along feeling, please answer the six questions yourself before continuing to read. When you are done, consider what a p-value actually is: A p-value is the probability of the observed data (or of more extreme data points), given that the null hypothesis H0 is true, defined in symbols as p(D |H0).Th is defi nition can be rephrased in a more technical form by introducing the statistical model underlying the analysis (Gigerenzer et al., 1989, chap. 3). Let us now see which of the six answers are correct:

Statements 1 and 3: Statement 1 is easily detected as being false. A significance test can never disprove the null hypothesis. Significance tests provide probabilities, not definite proofs. For the same reason, Statement 3, which implies that a significant result could prove the experimental hypothesis, is false. Statements 1 and 3 are instances of the illusion of certainty (Gigerenzer, 2002).

Statements 2 and 4: Recall that a p-value is a probability of data, not of a hypothesis. Despite wishful thinking, p(D |H0) is not the same as p(H0 |D), and a significance test does not and cannot provide a probability for a hypothesis. One cannot conclude from a p-value that a hypothesis has a probability of 1 (Statements 1 and 3) or that it has any other probability (Statements 2 and 4). Therefore, Statements 2 and 4 are false. The statistical toolbox, of course, contains tools that allow estimating probabilities of hypotheses, such as Bayesian statistics (see below). However, null hypothesis testing does not.

Statement 5: The “probability that you are making the wrong decision” is again a probability of a hypothesis. This is because if one rejects the null hypothesis, the only possibility of making a wrong decision is if the null hypothesis is true. In other words, a closer look at Statement 5 reveals that it is about the probability that you will make the wrong decision, that is, that H0 is true. Thus, it makes essentially the same claim as Statement 2 does, and both are incorrect.

Statement 6: Statement 6 amounts to the replication fallacy. Recall that a p-value is the probability of the observed data (or of more extreme data points), given that the null hypothesis is true. Statement 6, however, is about the probability of “significant” data per se, not about the probability of data if the null hypothesis were true. The error in Statement 6 is that p = 1% is taken to imply that such significant data would reappear in 99% of the repetitions. Statement 6 could be made only if one knew that the null hypothesis was true. In formal terms, p(D |H0) is confused with 1 – p(D). The replication fallacy is shared by many, including the editors of top journals. […] To sum up, all six statements are incorrect. Note that all six err in the same direction of wishful thinking: They overestimate what one can conclude from a p-value. […]

We posed the question with the six multiple-choice answers to 44 students of psychology, 39 lecturers and professors of psychology, and 30 statistics teachers […] How many students and teachers noticed that all of the statements were wrong? As Figure 1 shows, none of the students did. […] Ninety percent of the professors and lecturers also had illusions, a proportion almost as high as among their students. Most surprisingly, 80% of the statistics teachers shared illusions with their students.”

The article has much more.

iv. Diabetes in older Adults.

“More than 25% of the U.S. population aged [>65] years has diabetes (1), and the aging of the overall population is a significant driver of the diabetes epidemic. […] The incidence of diabetes increases with age until about age 65 years, after which both incidence and prevalence seem to level off”. I should have known the first number was in that neighbourhood, but somehow I had failed to realize that it was that high; most often prevalence estimates are calculated/reported using the entire population in the denominator, but of course such estimates can be deceiving if you do not think about how they are calculated and I clearly hadn’t. At least 1 in 4 in the above-65 age bracket. That’s a lot of people. The article doesn’t have a lot of data, it’s a ‘consensus report’ handling mostly various treatment guideline suggestions and similar stuff.

v. What is the most uncomfortable situation have you ever been put in- by a guy? Any kind of unwanted flirtation- or something of that nature (Reddit). Lots of really horrible stuff; reading stuff like this makes what might be perceived of as some females’ ‘somewhat overcautious’ behaviour towards members of the opposite sex easier to understand. An example from the link:

“The last stranger-danger moment I will share tonight was at an end-of-midterms party sponsored by the student union at a local bar. I was there with my best friend, and she’s very pretty and very friendly, so we’d very quickly attracted a group of four or five men who were hanging around with us for most of the night. I hadn’t seen any of them before, so I assumed they were students from a different department, and we end up getting a table together and talking for a while. Once my friend mentions that she has a boyfriend, most of them shift their attention to me, though there’s one who still seems interested in her. As I’m talking to them, I find that they’re not students at our university, but that they’re a group of friends visiting from the a couple towns over. Nothing too creepy, so far.

My friend finishes her drink, so the guy she’s talking to goes to buy her another. She’s a little suspicious, so she starts drinking it VERY slowly. Meanwhile, I’m getting distracted talking to one of the guys who works in the same field I’ll be entering soon, and we end up talking for a while about that. He keeps telling me that I’m very beautiful, which I keep brushing off because I knew he was interested in my friend initially, and I was interested in someone else at the time, anyway. Somewhere in the middle of all this, my friend has stopped drinking the drink that was bought for her, and someone asks if she’s going to finish it. She says no.

Eventually, the guy I’m talking to apologizes for his “bad” English, saying that he hasn’t really had to use it since he was in school, which was OVER TEN YEARS AGO. At about the same time, my friend is telling the guy she’s talking to that it’s funny that they decided to visit our city on that particular weekend, because this is a student end-of-midterm party, and he answers, “I know. That’s kind of why we came here.” Someone else asks my friend if she’s going to finish her drink, and she says no, but he can have it if he wants. The drink ‘accidentally’ gets spilled in the process, and she’s signalling me to get the fuck out of there, so I take the opportunity to drag her to the bathroom. I start to notice that she’s acting really fucked up – she can usually drink a ton more than I can, and she’d only had one drink of her own and maybe a third (probably less than that, actually) of the one that guy bought for her. She says she thinks the drink they gave her was drugged, and then she gets sick. I ended up staying the night at her place to keep an eye on her, but I didn’t think to take her to the hospital or anything, so I guess we’ll never know what exactly happened…”

Of course if you’re like me you don’t engage in risky behaviours like drinking with strangers and in that case it doesn’t really matter much if you’re male or female, but then again I’m not like normal people. Most males probably significantly underestimate how risky some of their behaviours – behaviours they would not ever even think of as ‘particularly risky’ – are when a female engages in them. Note that even males that fall into the “I can’t imagine you raising your voice”-category (a female friend said this about me in a conversation I had with her earlier today) are likely to be affected by the behaviours of the (type of) males described in the link; once a female has been through situations like the ones described at the link, she’s less likely to give males the benefit of the doubt and more likely to misinterpret behaviour and the motivations driving behaviour. Reading this stuff has made me believe that the behaviour of ‘overcautious’ females may be better justified and less ‘irrational’ than males tend to think it is.

vi. I haven’t commented on the new DSM-5 – let’s just say I’ve had better things to do. Here’s one take on it (“It’s arcane, contradictory and talks about invisible entities which no-one can really prove. Yes folks, the new psychiatric bible has been finalised.”). The most ‘relevant’ change to me is the fact that they’ll remove the Asperger Syndrome diagnosis, and instead merge it with other autism spectrum disorders. If you’re asking me what I think about that, the answer is that I don’t really care.

vii. Cheetahs on the Edge (via Ed Yong). A must-see:

“Using a Phantom camera filming at 1200 frames per second while zooming beside a sprinting cheetah, the team captured every nuance of the cat’s movement as it reached top speeds of 60+ miles per hour.

The extraordinary footage that follows is a compilation of multiple runs by five cheetahs during three days of filming.”

December 26, 2012 Posted by | autism, Biology, blogs, Diabetes, Language, Psychology, Random stuff, Statistics, Zoology | Leave a comment

Stuff

First of all, I’ve made a decision to try not to post too often over the next 2 months. Blogging takes time, doing stuff that’s blog-worthy takes time. I have a couple of important exams coming up in January. I should not be spending any of my time on the stuff that I blog about here before those exams are behind me.

Next, a few links.

i. Dying Outside, by Hal Finney. His last update is more than a year old. According to wikipedia, he’s still alive.

ii. What is a gene “for”?

““Scientists discover gene for autism” (or ovarian cancer, or depression, cocaine addiction, obesity, happiness, height, schizophrenia… and whatever you’re having yourself). These are typical newspaper headlines (all from the last year) and all use the popular shorthand of “a gene for” something. In my view, this phrase is both lazy and deeply misleading and has caused widespread confusion about what genes are and do and about their influences on human traits and disease.” […]

“While geneticists may know what they mean by the shorthand of “genes for” various traits, it is too easily taken in different, unintended ways. In particular, if there are genes “for” something, then many people infer that the something in question is also “for” something. For example, if there are “genes for homosexuality”, the inference is that homosexuality must somehow have been selected for, either currently or under some ancestral conditions. Even sophisticated thinkers like Richard Dawkins fall foul of this confusion – the apparent need to explain why a condition like homosexual orientation persists. Similar arguments are often advanced for depression or schizophrenia or autism – that maybe in ancestral environments, these conditions conferred some kind of selective advantage. That is one supposed explanation for why “genes for schizophrenia or autism” persist in the population.

Natural selection is a powerful force but that does not mean every genetic variation we see in humans was selected for, nor does it mean every condition affecting human psychology confers some selective advantage. In fact, mutations like those in the neuroligin genes are rapidly selected against in the population, due to the much lower average number of offspring of people carrying them. The problem is that new ones keep arising – in those genes and in thousands of other required to build the brain. By analogy, it is not beneficial for my car to break down – this fact does not require some teleological explanation. Breaking down occasionally in various ways is not a design feature – it is just that highly complex systems bring an associated higher risk due to possible failure of so many components.

So, just because the conditions persist at some level does not mean that the individual variants causing them do. Most of the mutations causing disease are probably very recent and will be rapidly selected against – they are not “for” anything.”

I have made a similar point in the past, probably more than once.

iii. Stuff you didn’t know about mine fires.

“Whether started by humans or by natural causes, coal seam fires continue to burn for decades or even centuries until either the fuel source is exhausted; a permanent groundwater table is encountered; the depth of the burn becomes greater than the ground’s capacity to subside and vent; or humans intervene. Because they burn underground, coal seam fires are extremely difficult and costly to extinguish, and are unlikely to be suppressed by rainfall.[1] There are strong similarities between coal fires and peat fires. […] Many recent mine fires have started from people burning trash in a landfill that was in proximity to abandoned coal mines, including the much publicized Centralia, Pennsylvania, fire, which has been burning since 1962. Of the hundreds of mine fires in the United States burning today, most are found in the state of Pennsylvania. […] It is estimated that Australia’s Burning Mountain, the oldest known coal fire, has burned for 6,000 years.”

In case you were in doubt, “Extinguishing underground coal fires, which sometimes exceed temperatures of 540°C (1,000°F), is both highly dangerous and very expensive.”

This is probably as good a place as any to once again remind old readers, and to let new ones in on this fact, that this blog is not one of those blogs that’ll just ‘die’ without an explanation. If I decide to close the blog down, I’ll tell you. If I haven’t told you anything and I also don’t update either the blog or my twitter in weeks, the most likely explanation is that I’m dead or something along those lines.

November 15, 2011 Posted by | autism, Genetics, Geology, meta, Personal, Random stuff | Leave a comment