A link between estrogen and autism

Drugs approved for autism, a neurodevelopmental disorder characterized by repetitive behaviors and social shyness, likely do not target its under-lying mechanisms. Because those remain a mystery to researchers, drug discovery works by testing hundreds of molecules on autistic animal models and watching for clues. Recently, a Yale-led team of scientists identified a potential winner: estrogen.

The team reported in February in Neuron that the flavonoid biochanin A, along with three other estrogenic compounds, seemed to reverse abnormal behavior in zebra fish carrying mutations in an autism risk gene.

To observe the drugs’ effects, the researchers, led by Ellen J. Hoffman, M.D., Ph.D., assistant professor in the Child Study Center, and Antonio J. Giraldez, Ph.D., professor of genetics, analyzed movements of zebra fish carrying a mutated gene called CNTNAP2, which is strongly linked to autism and epilepsy in Amish families. Estrogenic molecules suppressed hyperactivity at night—a manifestation of the disorder in zebra fish—but at no other time. This suggests the drugs were targeting a specific, though unknown, pathway of the disorder.

“These findings open the door to studies about how estrogen affects brain development,” Hoffman says.


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