EDINBURGH – Why should being male so markedly increase the likelihood of ending up with a diagnosis of an autism spectrum condition?

One explanation gaining increased traction as a result of multiple converging lines of evidence is the fetal testosterone theory of autism, Simon Baron-Cohen, Ph.D., said in the annual Blake Marsh Lecture at the meeting&nldr;

Dr. Baron-Cohen is the principal architect of the theory, which asserts that autism is linked to in utero exposure to very high levels of testosterone, with resultant extreme masculinization of the brain and mind. In other words, autism can be thought of as a case of “extreme male brain.”

“I think that this hormone–testosterone–at the fetal stage of development, and the genes that regulate it, may be part of the story.

“I don't suggest that it's all of the story because autism is complex and multifactorial. But this may be one of the factors to look at more carefully,” said Dr. Baron-Cohen, professor of developmental psychopathology and director of the autism research center at the University of Cambridge (England).

The prevalence of autism spectrum conditions in the general population is about 1%. Classic autism has a male to female ratio of 4:1, whereas in Asperger's syndrome it is 9:1.

Fetal testosterone levels are on average twice as high in males as in females. But levels vary up to 20-fold among male fetuses, he said.

Dr. Baron-Cohen and coworkers are conducting a landmark, ongoing, longitudinal study of 235 typically developing children whose fetal testosterone levels are known because their mothers underwent amniocentesis.

In a recent report, the investigators had parents rate their children for autistic traits at age 8 years using the Childhood Autism Spectrum Test and the Autism Quotient–Children's Version.

They found that the number of autistic traits that a child displayed was positively correlated with fetal testosterone level, independent of sex (Br. J. Psychol. 2009;100:1-22).

The hallmarks of autism spectrum conditions are social and communication difficulties, narrow interests, and extreme need for routine. Those characteristics can be viewed as extreme manifestations of inherently male interests and behaviors. In studies of spontaneous toy choice that have been replicated hundreds of times throughout the world, psychologists have shown that, given a choice, young boys will more often choose to play with toy vehicles and constructional toys such as Legos, whereas girls tend to be drawn more to dolls and emotional stories about them, Dr. Baron-Cohen said.

“On average, males' attention is more easily drawn to systems of one kind or another, and on average females' attention is more easily drawn to people and their emotional lives,” he continued.

These two psychological processes–empathy and systematizing–show clear sex differences in the population.

In other studies of the 8-year-olds with known fetal testosterone values, those with higher fetal testosterone scored lower on several different tests of empathy and higher on tests of systematizing and attention to detail than did children with lower fetal testosterone.

Earlier studies of this cohort demonstrated that at age 12 months, those with higher in utero testosterone were less likely to make eye contact with their mothers, and at age 2 years their vocabulary and language development were more limited than in the kids with lower fetal testosterone.

In other studies, Dr. Baron-Cohen's group, as well as other investigators, have shown that typically developing girls score higher than boys on tests of the cognitive aspects of empathy, and individuals with Asperger's syndrome score lower than either of the other groups.

Exactly the opposite was seen on psychological tests of systematizing and attention to detail.

Could these gender differences in interests and behavior simply be the result of cultural influences, such as social pressure on boys to become firemen and engineers and on girls to become nurses and elementary school teachers?

Dr. Baron-Cohen doesn't think so. He and his coworkers addressed this issue in a study of 24-hour-old babies. They placed two objects, one at a time, in the babies' hospital rooms: an image of a human face and a mechanical mobile. Then they filmed how long the babies looked at each. The girls tended to look longer at the face, whereas the boys were drawn to the mobile.

Another line of evidence supporting the fetal testosterone theory of autism comes from genetic studies done by Dr. Baron-Cohen's group.

They found that patients with Asperger's syndrome showed differences from controls in a set of more than a dozen sex steroid genes known to regulate testosterone production orabe involved in sex hormone transport.

Dr. Baron-Cohen's studies are funded by the U.K. Medical Research Council. He declared no financial conflicts.

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The number of autistic traits a child displayed was positively correlated with fetal testosterone level, independent of sex.

Source DR. BARON-COHEN

Fetal Testosterone Theory of Autism Gathering Steam