Autism, a developmental disorder that causes deficits in social behavior and communication, affects four times as many boys as girls. Because of this extreme gender imbalance, some scientists posit that sex hormones may contribute to the disease. Now researchers have identified for the first time a gene that may help explain the gender discrepancy and underlie some common autism symptoms.
In 2010 biologist Valerie Hu of the George Washington University Medical Center and her colleagues found that brains of people with autism have low levels of a protein produced by a gene called retinoic acid–related orphan receptor-alpha (RORA). Now they report in a study published in PLoS ONE on February 16 that this gene interacts with certain types of estrogen and testosterone found in the brain.
Hu and her team examined neural cells in their lab. They found that RORA controls the production of an enzyme called aromatase, which converts testosterone to estrogen. But in their tests, the presence of testosterone made RORA less active, leading to a decline in aromatase and a buildup of even more testosterone. Estrogen had the opposite effect. In a typical brain the balance of sex hormones regulates RORA activity and keeps hormone levels steady, but any imbalance can be exacerbated by this loop.
Next, the researchers confirmed that brain tissue from donors who had autism indeed contains low amounts of the RORA protein and aromatase. The authors suggest that a deficiency in these molecules causes the chemical loop to spiral out of control, resulting in an accumulation of testosterone that may cause autism. In most females, higher levels of estrogen could be protecting them from the disorder.
In addition to the gender bias, RORA might be implicated in the abnormal routines that characterize autism. For instance, mice that lack this gene fixate on objects and show limited exploratory behavior, similar to individuals with autism. “I don’t think any single gene is going to explain all of the pathology associated with autism, but RORA does explain quite a few of them,” Hu says.
This article was originally published with the title Why Autism Strikes More Boys Than Girls.
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6 Comments
Add CommentHas anybody tested the effect of anti-testosterons ie Lucrin on the test mice with autism-like syndrome?
Reply | Report Abuse | Link to thisI am not wholly convinced that autism as a predomanantly "male" affliction is due to estrogen DEFICIENCY in the brain. Hormones affect both sexes and categorically calling estrogen the "female" hormone is limited in scope. And this is becoming more obvious as science progresses.
Reply | Report Abuse | Link to thisThere was a recent discovery in the male HUMAN brain via aromatase tracing through an inhibitor (vorozole) that identified areas of aromatase expression not previously seen in animal models. Scientists want to discover if this variance (high vs. low levels) is linked to pathological aggression, future dementia risk, and autism. Now autism of course, in its extreme, results in lack of verbal ability and mute-ness. But does estrogen PROTECT against these verbal deficiencies? Well, the available data, at least in older women, say otherwise, where estrogen replacement decreases verbal memory, shrinks the brain, and raises dementia risk. And some intriguing prostate cancer data in men being treated with androgen deprivation therapy showed that it was the drop in estradiol, NOT testosterone, that led to WORSE visuospatial ability but IMPROVED verbal memory.
I'm also struck by what is simply called "roid rage" where athletes and bodybuilders abuse anaboloic, androgenic steroids. What seems to be missed in the scientific discourse is that as T-levels rise, so does estrogen, which gives rise to the obvious side effects of gynecomastia and genital atrophy. But might the raised estrogen via increased aromatization also explain some of the psychological effects?
All in all, I personally am doubtful that testosterone, which gets blamed for all negative things "male", is at the root of autism. Frankly, I suspect it is dysregulated high estrogen that might be a silent player. But we'll see as time goes on....
Could it be that something in the environment effects the functioning of the "aromatase enzyme" and therefore those most severly effected don't have any estradiol to plug into their receptors at all. Maybe because females have other estrogen it compensates in some way that the brain just uses other parts more.
Reply | Report Abuse | Link to thisThat is an interesting theory. For a long time people have thought that the difference was due to better diagnosis in boys, with girls "slipping through the cracks" due to being able to "pass" better. That still may be some of the reason, but this would explain the rest of the picture. This is the first article I have seen suggeting an actual biochemical explanation. Here is an interesting radio interview I found on the subject of girls with autism
Reply | Report Abuse | Link to thishttp://www.aspergerssociety.org/articles/20.htm
We are getting further and further in our quest to explain the causes of autism, it seems, which is a good thing.
I wondder why this world has so many ways to kill someone but not eought to save someone.
Reply | Report Abuse | Link to thisYes I agree myself why.... this world sucks...
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