tag:blogger.com,1999:blog-6146376483374589779.post389016659276822800..comments2024-02-14T11:18:50.296-08:00Comments on Wiring the Brain: Autism: The Truth is (not) Out There Kevin Mitchellhttp://www.blogger.com/profile/07172255754953214162noreply@blogger.comBlogger7125tag:blogger.com,1999:blog-6146376483374589779.post-62858829436121662502016-03-23T06:26:38.381-07:002016-03-23T06:26:38.381-07:00Also Kevin Mitchell, you wrote, "you'd ha...Also Kevin Mitchell, you wrote, "you'd have to additionally explain why rates of schizophrenia are not also increasing". Since autism is associated with a higher risk of schizophrenia, and autism rates are increasing, if we waited twenty years for the boys, and thirty-five years for the girls, I think we would see an increase in schizophrenia rates. Tootiehttps://www.blogger.com/profile/03249516637029480332noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-22883024942154678122014-10-31T08:27:52.839-07:002014-10-31T08:27:52.839-07:00I should also say that all the environmental risk ...I should also say that all the environmental risk factors that have been identified in epidemiological studies are also associated with statistically increased risk of schizophrenia and neurodevelopmental disorders more generally. Thus, if one is appealing to changes in those kinds of factors as an explanation for increasing rates of autism diagnoses, you'd have to additionally explain why rates of schizophrenia are not also increasing.Kevin Mitchellhttps://www.blogger.com/profile/07172255754953214162noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-47197555664504188412014-10-31T08:25:32.398-07:002014-10-31T08:25:32.398-07:00Thanks Dwight, for your comments. Regarding possib...Thanks Dwight, for your comments. Regarding possible intra-uterine effects, I agree they may be important and, in some cases, could even be causal (like with valproate, for example). But I also think they are not likely to be of major importance as causes or sources of variance across the population, due to the twin and family studies, which all show much higher concordance in MZ than DZ twins. I see little reason to think that an external environmental factor (external to the twins, that is) would have more shared effect on MZ than DZ twins. These studies also consistently show no effect of a shared family environment.<br /><br />John McGrath has written a chapter on environmental factors (and gene by envt interactions) for an upcoming book that I am editor of on The Genetics of Neurodevelopmental Disorders. He covers many epidemiological findings of "risk factors" which include the ones you list above and others (obstetric complications, maternal infection). Most show very modest effects and the problem with epidemiological studies is that inferring causation and eliminating confounds are both effectively impossible.Kevin Mitchellhttps://www.blogger.com/profile/07172255754953214162noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-66557693759773445022014-10-31T08:16:03.416-07:002014-10-31T08:16:03.416-07:00Thanks for the excellent piece, Kevin. I'd li...Thanks for the excellent piece, Kevin. I'd like to draw you out a bit further regarding the role of environmental influences. After being a doubter, I've grown more agnostic regarding the possibly increasing prevalence of autism, but it's not my area. I wasn't aware of the trend toward decreasing MR dx's. That should certainly be part of the discussion. But leaving that debate aside, it still seems that environmental effects -- mainly intra-uterine -- get short shrift. The 77% unexplained etiology (and the similar number in schizophrenia, which I know more about) stands out. I'd probably argue, gloomily, that what we know about etiology for both categories is probably considerably less than those percentages suggest. <br /><br />I agree that twin studies offer strong support for genetic etiology, but it seems that twin study commentary downplays some well-known differences and variations in the intra-uterine experience of mono- vs dizygotic twins. Most agree that autism and schizophrenia are neurodevelopmental disorders. And it is fairly clear that a developing human is never more environmentally sensitive and plastic than during the nine months after conception, which, presumably, makes us subject to subtle developmental 'butterfly effects.' John McGrath (among others) has written persuasively about a number of environmental gradients that may influence gestation in schizophrenia – e.g., rural to urban, summer to winter (or dark to light), immigrant status. How many variables might be in play? Nutrition, vitamins, hormones, activity levels, social stress, differences in allergens and pathogens, immune system activation – and all interacting dynamically with genetics. I don't know the autism literature about these sorts of gestational influences. But I feel about this area like I feel about complex genetic interactions -- even in the absence of good evidence and adequate analytical tools, it has to be critical. <br />Dwight Dickinsonhttps://www.blogger.com/profile/04859350935463265585noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-61591840295253483852014-10-24T16:17:01.795-07:002014-10-24T16:17:01.795-07:00What about countries like Italy where autism is st...What about countries like Italy where autism is still largely unheard of or seen. Italy is an interesting case as it's one of the very few modern countries that still eat fresh food as standard and have very close family bonds. A.https://www.blogger.com/profile/03584985012740841368noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-81868868474927923372014-10-20T00:00:52.450-07:002014-10-20T00:00:52.450-07:00Twin studies do control for the environment, espec...Twin studies do control for the environment, especially for things like maternal exposures. If these were causing autism, then dizygotic twins should both be affected at the same rate as monozygotic twins. <br /><br />Epidemiological studies have found slightly increased risk of autism with maternal infection or obstetric complications - however, these statistical effects are minor when compared with the overall genetic effects. (In addition, obstetric complications may be an effect rather than a cause of a neurodevelopmental disorder). <br /><br />Moreover, those factors are correlated with increase risk for other disorders too, such as schizophrenia and intellectual disability. If one is appealing to them to explain the apparent rise in autism (diagnoses), then one would have to explain why those other disorders are not also rising in prevalence. Kevin Mitchellhttps://www.blogger.com/profile/07172255754953214162noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-35540089556389370092014-10-19T21:56:37.991-07:002014-10-19T21:56:37.991-07:00The theory presented in this article relies upon t...The theory presented in this article relies upon the assumption that twin studies control for environment. However, several studies have shown this assumption does not hold. http://www.ncbi.nlm.nih.gov/pubmed/16238870<br />Furthermore, this article fails to acknowledge the work of several groups that have shown strong correlations between maternal infection, maternal autoimmune disease, maternal antibodies aimed at fetal brain proteins, proximity to high levels of pollution, etc. It is unwise to rule out an environmental component simply because of several "undead memes".Anonymoushttps://www.blogger.com/profile/08144774030759012966noreply@blogger.com