Compelling evidence for autism-antidepressant link

Rodents exposed to a common serotonin reuptake inhibitor (SSRI) antidepressant just before and after birth exhibited brain abnormalities and behaviors – such as novelty avoidance and social impairment – commonly associated with autism. The research suggests that taking antidepressants during pregnancy might be one factor contributing to the dramatic rise in autism spectrum disorders in children. The incidence of pregnant women taking SSRIs has grown from around 0.5 percent in 1985 to nearly 10 percent today.

The new work builds on earlier research this year that reported an association between mothers taking antidepressants and increased autism risk in their children. The results of the new multi-center study, funded by the National Institutes of Health, appear in the journal Proceedings of the National Academy of Sciences.

For the study, the researchers treated more than 200 rats with the popular SSRI citalopram during key stages of brain development. Rats are born at an earlier developmental stage than humans, equivalent to the end of the sixth month of fetal development in humans. Most rats received treatment for two weeks, beginning eight days post birth, a neurodevelopment period equivalent to the third trimester and early infancy in humans.

In contrast with the control-group rats, the researchers found that the treated rodents were uninterested in play when young and displayed poor social behaviors as adults. The treated rats also showed abnormal responses to changes in their environment. “These results demonstrate that rat pups, when exposed perinatally to SSRIs, exhibit behavioral traits often seen in autism spectrum disorders,” said Kimberly Simpson, the study’s first author and University of Mississippi associate professor of neurobiology.

Interestingly, the behaviors occurred more often – and sometimes exclusively – in the treated male rats than in treated females. Similarly, autism spectrum disorder is diagnosed more often in males.

Physiologically, the researchers found that a key brain serotonin circuit, the raphe system, known to shape the developing brain during the critical period when the animals were exposed to the drug, showed dramatic reductions in density of neuronal fibers. Evidence of stunted development in the circuit was apparent through much of the cortex and other regions important for thinking and emotion, such as the hippocampus.

The study also documents miswiring in the structure responsible for communications between the brain’s left and right hemispheres (the corpus collosum). Additionally, axons, through which such long-distance communications are conducted, were deformed. A protective sheath, called myelin, that normally wraps and boosts axons’ efficiency was reduced by one-third in the treated animals. This damage was three times worse in male than in female pups and would likely result in disrupted communication between the two hemispheres, according to the researchers.

Principal investigator Rick C.S. Lin, professor of neurobiology at the University of Mississippi, cautioned that pregnant women shouldn’t quit taking prescribed antidepressants based solely on the study’s results. “In this study we eliminated as many external factors as possible. But real-life situations are much more complex. We need to know which one causes minimal damage but also at what dose, for how long and at what points in pregnancy. We still have a lot to learn,” he concluded.

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Source: University of California – San Francisco, National Institute of Mental Health

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