Dan Gorodezky

A Yale-led study may point toward future treatments for autism, though researchers said human application is still a long way off.

The study was led by researchers at Yale, the University of California, San Francisco and University College London. It found that estrogens, the primary female sex hormone, could reverse abnormal behavior in zebrafish carrying a mutation in CNTNAP2, a gene linked to autism in humans. The finding interested the researchers because males are four times more likely than females to be diagnosed with autism. The study was published in the journal Neuron on Jan. 28.

“Autism is much, much more prevalent in men than in women, and we have no idea why that is the case, as far as I know,” professor of genetics and co-senior author Antonio Giraldez said. “So it was really exciting that one compound … was able to suppress [the abnormal behavior].”

The researchers found that zebrafish carrying the CNTNAP2 mutation are hyperactive at night and more prone to seizures than zebrafish without the mutation. Through a process known as quantitative behavioral profiling, they established profiles of normal zebrafish exposed to more than 500 different drugs and used those to predict which drugs would suppress the abnormal behavior. The researchers found that drugs that behave like estrogens stopped the nighttime hyperactivity and seizures.

Zebrafish provide a good model for this type of study, the researchers said, because their transparent bodies allow researchers to observe key parts of their brain development and because their high reproductive rate makes working with large numbers fairly convenient.

“They’re really a very advantageous model system for translational research,” senior author and Child Study Center professor Ellen Hoffman GRD ’14 said.

Though the researchers were excited about the results of the study and what it might mean for future autism treatments, both Giraldez and Hoffman cautioned that much additional research stands between this study’s findings and application to human patients. The researchers will next need to pursue further studies on other mammalian systems, such as mice, Hoffman said.

“If we go in a very not-careful way and we say, ‘Well, this cures autism in fish,’ what we will have is tons of parents giving estrogens to their kids — and that is very dangerous,” Giraldez said. “This is not to be tested in humans yet.”

Janghoo Lim, a Yale professor of genetics and neuroscience who has conducted similar research involving autism spectrum disorders, echoed the researcher’s caution. He also praised the profiling system the researchers used to produce the study, and said he is excited to see where it leads in terms of other research.

About 1 in 68 children in the U.S. in 2010 were identified as having autism, according to the Centers for Disease Control and Prevention.