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The genetics of autism

Autism and autism spectrum disorders (ASDs) actually represent a rather large continuum of conditions that range from very severe neurodevelopmental delay and abnormalities to the relatively mild. In severe cases, the child is nonverbal and displays a fairly well-characterized set of behaviors, including repetitive behaviors such as “stimming” (for example, hand flapping, making sounds, head rolling, and body rocking.), restricted behavior and focus, ritualistic behavior, and compulsive behaviors. In more mild cases, less severe compulsion, restriction of behavior and focus, and ritualistic behaviors do not necessarily preclude functioning independently in society, but such children and adults may have significant difficulties with social interactions and communication. Because ASDs represent a wide spectrum of neurodevelopmental disorders whose symptoms typically first manifest themselves to parents between the ages of two and three, the idea that vaccines cause autism and ASDs has been startlingly difficult to dislodge and has fueled an anti-vaccine movement, both here in the U.S. and in other developed nations, particularly the U.K. and Australia. This movement has been stubbornly resistant to multiple scientific studies that have failed to find any link between vaccines in autism or the other favorite bogeyman of the anti-vaccine movement, the mercury-containing thimerosal preservative that used to be in many childhood vaccines in the U.S. until the end of 2001. Add to that the rising apparent prevalence of ASDs, and, confusing correlation with causation, the anti-vaccine movement concludes that vaccines must be the reason for the “autism epidemic.”

In reality, autism and ASDs appear to be increasing in prevalence due to diagnostic substition, better screening, and the broadening of the diagnostic criteria that occurred in 1994. Autism prevalence does not appear to be rising, at least not dramatically, at all, as the prevalence of ASDs, when assessed carefully, appears to be similar in adults as it is in children. If the true prevalence rate of autism and ASDs has increased, it has not increased by very much. In reality autism appears to have a major and probably predominant genetic component, and several scientific studies over the last few years have linked autism with various genetic abnormalities. Not surprisingly, given the varied presentation and severity of ASDs, these studies have not managed to identify single genes that produce autism or ASDs with a high degree of penetrance (probability of causing the phenotype if the gene is present). Indeed, one can argue that the state of current evidence is that ASDs are due to multiple genes, perhaps dozens or hundreds. Again, this is not surprising given the heterogeneity of ASD severity, presentation, and symptoms.

One of the more surprising studies supporting a genetic basis for autism appeared to much fanfare in Nature last week. The study by Pinto et al, looks at the functional impact of global rare copy number variation in autism spectrum disorders. Its results are rather surprising in that the large team of investigators (studies of this type take a lot of people to carry out) found that it may be relatively uncommon copy number variations in various genes that lead to the phenotype of autism or ASDs.
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Posted in: Neuroscience/Mental Health, Science and Medicine, Vaccines

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In which Dr. Gorski once again finds himself a target of the “pharma shill” gambit

EDITOR’S NOTICE: NOTE THE DISCLAIMER. Also note that there is a followup to this post entitled The price of opposing medical pseudoscience that is highly recommended after you read this post.

The “pharma shill gambit”: The quack’s favorite flavor of ad hominem argument

One of the very favorite and most commonly used tactics to attack criticism in the armamentarium of pseudoscientists, cranks, and quacks (not to mention politicians) is the ad hominem fallacy. In this fallacy, rather than addressing the actual evidence and science that demonstrate their favorite brand of woo to be nothing more than fairy dust, the idea is to preemptively attack and discredit the person. The ad hominem is not just insults or concluding that someone is ignorant because, well, they say ignorant things and make stupid arguments (in which case calling someone stupid or ignorant might just be drawing a valid, albeit impolitic, conclusion from observations of that person’s behavior), but rather arguing or insinuating that you shouldn’t accept someone’s arguments not because their arguments are weak but because they have this personal characteristic or that or belong to this group or that. Truly, the ad hominem is right up there with demanding public “debates” with skeptics as a favored defense strategy of cranks of all stripes.

Among the very favorite flavors of ad hominem attack used by quacks, cranks, and pseudoscientists is the fallacy of poisoning the well. This particular fallacy alludes to the medieval European myth that the Black Plague was caused by Jews poisoning town wells. Not surprisingly, this myth was used as a justification for pogroms and the persecution of the Jews. The idea is to poison how others view your opponent by preemptively attacking them. Well do I know this fallacy, having been at the receiving end of it many times! Basically, it involves invoking something bad or biased about a person’s situation or personality and then using a phrase something like, “Of course he (or she) would say that” to dismiss a person’s arguments, the implication being that the person receives such benefits from holding the position being attacked or has such a personality that he couldn’t argue otherwise regardless of the evidence. In my admittedly anecdotal experience, far and away the most common use of the ad hominem from quacks and pseudoscientists is what I once described as “the pharma shill gambit.” The idea behind this gambit when it comes to attacking those of us who promote science-based medicine is to tar one’s opponent as being a “shill” for big pharma or claiming that we have a conflict of interest so blatant that “of course we would say that.” In most cases, the bogey man is big pharma, in whose pockets we SBM bloggers are supposed to be safely (and profitably) ensconced, blogging away in our underwear for big bucks and, following the orders of our supposed paymasters, attacking anything that has even a whiff of being “alternative” or that “questions” the safety and/or efficacy of vaccines.

While I realize that there is such a thing as an “astroturf” campaign, in the vast majority of cases, the pharma shill gambit is nothing more than the variant of the ad hominem fallacy known as poisoning the well. I also realize that conflicts of interest (COIs) matter, particularly undisclosed COIs. Indeed, I wrote a rather lengthy post (I know, I know, do I write any other length of post?) about 8 months ago laying out my views regarding COIs in science-based medicine. The short version is that we all have COIs of some sort or another, be they financial, belief-based, or emotional, and more disclosure is usually better, to let the reader decide for himself. As far as COIs related to big pharma or finances, I think Mark Crislip put it quite well in his most recent Quackcast when he said that if a study is funded by big pharma, he decreases the strength of the evidence in his mind by a set amount. However, evidence is evidence, and, although it is reasonable to increase one’s level of skepticism if there is a major COI involving the authors, be it big pharma or otherwise, it is not reasonable to use that COI as the sole reason for rejecting its findings out of hand. That’s just an intellectually lazy excuse to dismiss the study, nothing more. Indeed, one prominent difference between a scientist and a pseudoscientist or quack is that in general scientists understand this and struggle to assign the correct degree of skepticism due to a COI when analyzing scientific studies, while quacks and pseudoscientists do not. It’s far easier for them just to put their fingers in their ears and scream “Conflict of interest! Conflict of interest!” and then use that to dismiss completely their opponent’s argument. It’s simple, neat, and it doesn’t require all that nasty thinking and weighing of evidence..
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Posted in: Medical Ethics, Neuroscience/Mental Health, Public Health, Vaccines

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Certainty versus knowledge in medicine

I don’t want knowledge. I want certainty!

— David Bowie, from Law (Earthlings on Fire)

If there’s a trait among humans that seems universal, it appears to be an unquenchable thirst for certainty. It is likely to be a major force that drives people into the arms of religion, even radical religions that have clearly irrational views, such as the idea that flying planes into large buildings and killing thousands of people is a one-way ticket to heaven. However, this craving for certainty isn’t expressed only by religiosity. As anyone who accepts science as the basis of medical therapy knows, there’s a lot of the same psychology going on in medicine as well. This should come as no surprise to those committed to science-based medicine because there is a profound conflict between our human desire for certainty and the uncertainty that is always inherent in so much of our medical knowledge. The reason is that the conclusions of science are always provisional, and those of science-based medicine arguably even more so than many other branches of science.

In fact, one of the hardest things for many people to accept about science-based medicine is that the conclusions of science are always subject to change based on new evidence, sometimes so much so that even those of us “in the biz” can become a bit disconcerted at the rate at which knowledge we had thought to be secure changes. For example, think of how duodenal peptic ulcer disease was treated 25 years ago and then think about how it is treated now. Between 1984 and 1994, a revolution occurred on the basis of the discovery of H. pylori as the cause of most of the gastric and peptic ulcer disease we see. Where in 1985 we treated PUD with H2-blockers and other drugs designed to block gastric acid secretion, now antibiotics represent the mainstay of treatment and are curative at a much higher success rate than any treatment other than surgery and without the complications of surgery. I’m sure any other physician here could come up with multiple other examples. In my own field of breast cancer surgery, I look back at how we treated breast cancer 22 years ago, when I first started residency, and how we treat it now, and I marvel at the changes. If such changes can be disconcerting even to physicians dedicated to science-based medicine, imagine how much more disconcerting they are to lay people, particularly when they hear news reports of one study that produces one result, followed just months later by a report of a different study that gives a completely different result.
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Posted in: Diagnostic tests & procedures, Medical Academia, Neuroscience/Mental Health

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Potential New Mechanism of Pain Relief Discovered

The development of drugs and other treatments for specific symptoms or conditions relies heavily on either serendipity (the chance finding of a beneficial effect) or on an understanding of underlying mechanisms. In pain, for example, there are limited ways in which we can block pain signals – such as activating opiate receptors or inhibiting prostaglandins. There are only so many ways in which you can interact with these systems. The discovery of a novel mechanism of modulating pain is therefore most welcome, and has the potential of leading to entirely new treatments that may have better side-effect profiles than existing treatments and also have additive clinical effects.

A recent study by Nana Goldman et. al., published in Nature Neuroscience, adds to our understanding of pain relief by identifying the role of adenosine in reducing pain activity in the peripheral nervous system. The researchers, in a nice series of experiments, demonstrated that producing a local painful stimulus in mice causes the local release of ATP (adenosine triphosphate) that peaks at about 30 minutes. This correlates with a decreased pain response in the mice. Further, if drugs are given that prolong the effect of adenosine, the analgesic effect itself is prolonged.

Also, if drugs are given that activate the adenosine A1 receptor, the observed analgesic effect is replicated. When these experiments are replicated in knockout mice that do not have the gene for the adenosine A1 receptor, there is no observed analgesic effect.

Together these experiments are fairly solid evidence that local pain results in the local release of adenosine that in turn binds to the adenosine A1 receptor inhibiting the pain response. This is potentially very exciting – it should lead to further investigation of the adenosine A1 receptor and the effects of activating and inhibiting it. This may lead to the development of drugs or other interventions that activate these receptors and may ultimately be a very useful addition to our ability to treat acute and chronic pain.

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Posted in: Acupuncture, Neuroscience/Mental Health

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Stand up for science-based medicine against anti-vaccine fear mongering in Chicago today

As I’ve pointed out numerous times this week, anti-vaccine loons, led Generation Rescue and a “health freedom” group, have organized an anti-vaccine rally in Grant Park in Chicago from 3 PM to 5 PM CDT. Andrew Wakefield himself will be the keynote speaker, and there will even be some very bad music promoting the anti-vaccine message. The rally, with its wonderfully Orwellian title, The American Rally for Personal Rights, will be pure anti-vaccine activism in support of pseudoscience on display.

Those supporting science-based medicine plan, led by Skepchick Elyse Anders, to be there to promote science over the conspiracy theories and fear mongering that the anti-vaccine movement uses to frighten parents out of vaccinating their children. I realize it’s short notice. I realize that you very likely will be outnumbered, given the combination of short notice and the fact that the anti-vaccine zealots have been organizing and promoting this rally for weeks, if not months. Nonetheless, you’ll be doing me a particular solid if you can show up there. Details are here. There are also going to be satellite rallies in New Jersey, Washington, and New York. They look as though they’ll be much smaller; so, as P.Z. Myers points out, even if a couple of people can go it could have an effect.

Oh, and if you see J.B. Handley, Jenny McCarthy (I don’t know if she’ll be there or not but thought I’d mention her anyway), Andrew Wakefield, Kim Stagliano, or any other prominent anti-vaccine loon with whom I’ve tussled from time to time here and elsewhere, please tap him or her on the shoulder, smile broadly, and tell ‘em Dr. Gorski says hi.

Particularly J.B. Handley, for at least three reasons1,2,3.

Posted in: Neuroscience/Mental Health, Vaccines

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Autism One: The yearly antivaccine autism “biomed” quackfest begins

In the world of the anti-vaccine underground, there is one time of the year that looms large. Over the last few years, this time has generally come right around the end of May, usually coinciding with the Memorial Day weekend and the unofficial beginning of the summer vacation season here in the U.S. I’m referring, of course, to Autism One, which blights one of my favorite cities in the world, Chicago, every year about this time. True, of late Autism One has been metastasizing, most recently to blight the city of Toronto and the very grounds of the University of Toronto itself. As you may recall, last fall, when Autism One descended upon Toronto, I described it as “a conference of believers in two things: (1) that vaccines cause autism and (2) that ‘biomedical’ and CAM/IM therapies can treat and even reverse autism,” and it’s true, but Autism One is more than that. It’s a combination of a networking meeting for the anti-vaccine set, a revival meeting for the cult of anti-vaccinationism and autism “biomedical” therapy, and a trade show for “biomed” treatments for autism, all dressed up to appear to be a legitimate scientific conference.

Of all the fake scientific conferences out there, Autism One in Chicago, which begins today, far eclipses all the others, including even Barbara Loe Fisher’s National Vaccine Information Center (NVIC) conference. Closely aligned with the anti-vaccine propaganda group Generation Rescue and its outlet in the blogosphere Age of Autism (both of which, not surprisingly, have been promoting the conference incessantly), Autism One is the granddaddy of fake academic autism conferences, where anyone who’s anyone in the anti-vaccine “autism biomed” underground goes to see and be seen. It even has a keynote address by anti-vaccine celebrity spokesmodel Jenny McCarthy herself this year, just like the previous two years. This year, however, Autism One has expanded from three or four days to a full week, and it has taken on a note of political activism that was generally lacking in previous conferences. In previous years, Autism One pretty much stayed localized to a hotel near O’Hare, far from the center of the city. This time around it’s still at a hotel near O’Hare, but its organizers plan an anti-vaccine protest rally right smack dab in the middle of Grant Park on Wednesday afternoon. All of this leads me to conclud that this year Autism One’s organizers appear to be cementing the relationship between the autism “biomed” movement, the anti-vaccine movement, and the “health freedom” movement.
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Posted in: Neuroscience/Mental Health, Politics and Regulation, Vaccines

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Brain-Training Products Useless in Study

The health marketplace has a life of its own, mostly separated from science and evidence. Generally the marketplace gets a hold of an idea and runs with it, before the science is carefully worked out. Since most new ideas in science turn out to be wrong, that means most products will eventually be found to be worthless.

One such idea is that “brain training” can improve overall cognitive function – so of course now there is an industry of products which claim to train your brain. Lumosity (just to pick a random example served up by Google) claims on their website:

Brain Train
SCIENTIFICALLY DESIGNED

* Improve memory and attention
* Shown to improve cognitive function
* Neuroscience based brain training
* Train your brain today

I always enjoy the phrase “scientifically designed” or “scientifically formulated” – they are wonderful marketing phrases that invoke “science” without making any specific claims.

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Posted in: Neuroscience/Mental Health

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Social Factors in Autism Diagnosis

There is no question that the incidence and prevalence of autism are on the rise. Starting in the early 1990s and continuing to today, there has been a steady rise in the number of children diagnosed with autism. Prior to 1990 the estimates of autism prevalence were about 3 per 10,000. The most recent estimates from the CDC and elsewhere now have the number at about 100 per 10,000, or 1%.

The burning question is – why are the rates increasing steadily? There are those, particularly in the anti-vaccine community, who conclude that the increase in prevalence is a real biological effect – an epidemic – and is evidence for an environmental cause (which they believe is vaccines, even though the scientific evidence does not support this position). However, the evidence strongly suggests that the rising prevalence of autism is largely an artifact of broadening the diagnosis and increased surveillance.

It should be noted that the data cannot rule out a small true increase in autism prevalence. Some hypothesize that increasing maternal and paternal age are contributing to the incidence of autism, but I will leave that question for another post.

A new study now adds significant support to the surveillance hypothesis – Ka‐Yuet Liu, Marissa King, and Peter S. Bearman from Columbia University, publishing in the American Journal of Sociology, report that the risk of being diagnosed with an autism spectrum disorder (ASD) correlates with social proximity to another family with a child with an ASD diagnosis. For those interested in this topic, the full paper is worth a read. While it gets technical at times, the authors do an excellent job of reviewing this topic in detail.

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Posted in: Neuroscience/Mental Health, Vaccines

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Steven Higgs: Another antivaccine reporter like Dan Olmsted in the making?

April is National Autism Awareness Month, and as of today April is nearly half over. Do you notice anything different compared to the last couple of years? I do. Can you guess what it is?

The anti-vaccine movement’s usual suspects haven’t been all over the mainstream media, as they usually are this time every year, often as early as April 1 or even March 31. In fact, over the last couple of years I had come to dread April 1, not because it’s April Fools’ Day (although the things that made me dread that particular day were often indistinguishable from an April Fools’ Day prank, so full of idiocy were they), but rather the expected carpet bombing of the media by the likes of Jenny McCarthy, J. B. Handley, and their ilk, some or all of whom would show up on various talk shows to spread their propaganda that vaccines cause autism. For instance, last year Jenny McCarthy and her former boyfriend Jim Carrey showed up on Larry King Live! with Dr. Jerry Kartzinel (her co-author on her latest book of autism quackery) and J. B. Handley, the last of whom even contributed a guest post on Larry King’s blog, in which he touted an incredibly bad, pseudoscientific “study” commissioned by Generation Rescue. The “study” (and calling it a “study” is way too generous) was no more than cherry-picked random bits of data twisted together into a pretzel of nonsense, as I described. Around the same time, Jenny McCarthy was interviewed by TIME Magazine, an interview in which she uttered these infamous words:

I do believe sadly it’s going to take some diseases coming back to realize that we need to change and develop vaccines that are safe. If the vaccine companies are not listening to us, it’s their fucking fault that the diseases are coming back. They’re making a product that’s shit. If you give us a safe vaccine, we’ll use it. It shouldn’t be polio versus autism.

Soon after, Generation Rescue created a website called Fourteen Studies, which they promoted hither, thither, and yon. The idea of the website was to attack the main studies that failed to find a link between vaccines and autism and to promote the pseudoscientific studies that anti-vaccinationists like. In 2008, it was pretty much the same — well, worse, even. When she appeared on Larry King Live! with our old “friend,” anti-vaccine pediatrician to the stars, Dr. Jay Gordon, McCarthy shouted down real experts by yelling, “Bullshit!” (behavior trumpeted by Rachel Sklar of the Huffington Post).

This year? Oddly enough (and to me unexpectedly), there’s been almost nothing. J.B. Handley seems to be the man who wasn’t there. Well, not quite. It turns out that J. B. Handley has managed to get a little bit of fawning media attention, but just a little bit, in the form of an interview in The Bloomington Alternative entitled J. B. Handley: It’s unequivocal; vaccines hurt some kids. Apparently Mr. Handley has come down quite a bit in the world. Where’s his appearance with Jenny on Larry King Live! this year? Maybe it’s coming in the second half of the month. Or maybe the mainstream media, in the wake of the fall of Andrew Wakefield, have finally figured out how disreputable Generation Rescue is when it comes to vaccines. In the meantime Steven Higgs will have to do as a new mouthpiece for the anti-vaccine movement.

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Posted in: Neuroscience/Mental Health, Science and the Media, Vaccines

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Acupuncture for Depression

One of the basic principles of science-based medicine is that a single study rarely tells us much about any complex topic. Reliable conclusions are derived from an assessment of basic science (i.e prior probability or plausibility) and a pattern of effects across multiple clinical trials. However the mainstream media generally report each study as if it is a breakthrough or the definitive answer to the question at hand. If the many e-mails I receive asking me about such studies are representative, the general public takes a similar approach, perhaps due in part to the media coverage.

I generally do not plan to report on each study that comes out as that would be an endless and ultimately pointless exercise. But occasionally focusing on a specific study is educational, especially if that study is garnering a significant amount of media attention. And so I turn my attention this week to a recent study looking at acupuncture in major depression during pregnancy. The study concludes:

The short acupuncture protocol demonstrated symptom reduction and a response rate comparable to those observed in standard depression treatments of similar length and could be a viable treatment option for depression during pregnancy.

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Posted in: Acupuncture, Clinical Trials, Neuroscience/Mental Health, Obstetrics & gynecology

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