At the recent annual meeting of the Society for Neuroscience, which was held in San Diego from November 13-17, four poster presentations told of how, in animal studies, early exposure to psychiatric medications impaired normal brain development. After the animals matured into adults, they showed deficits in functioning, even though their “childhood” or “fetal” exposure to the psychiatric drugs had been relatively brief.
SSRIs and Fetal Brain Development
Researchers from the University of Washington studied the effects of an antidepressant, citalopram (Celexa,) on the development of the fetal mouse brain. During embryonic development, many brain regions experiences waves of spontaneous depolarizations called “spontaneous synchronous activity” (SSA). This activity plays an important role in the formation of neuronal circuits. The researchers found that fetal exposure to citalopram altered this SSA activity in the hindbrain, which is where serotonergic raphe neurons originate.
The University of Washington scientists concluded that “this aberrant and persistent pattern of SSA in the citalopram-treated embryonic hindbrain suggests a potentially adverse effect of acute SSRI exposure on fetal hindbrain development, and specifically on the serotonin neuron circuitry itself.”
SSRIs and Breast Feeding
In this study, by researchers at St. Mary’s College of Maryland, male rat pups were exposed to fluoxetine through dam’s milk (i.e. lactation), for 13 days, starting when they were eight days old. The baby rats were then allowed to “mature undisturbed until adulthood.”
As adults, the researchers reported, the rats were much clumsier than normal. “These results,” the researchers concluded, “indicate that postnatal exposure to fluoxetine may have long-term emotional and motor side effects.”
Antipsychotics and Long-Term Behavioral Dysfunction
In two related studies, investigators at the University of Maryland and the University of Lethbridge in Canada focused on the long-term effects of early exposure to olanzapine (Zyprexa.)
In the first study, rats were exposed to olanzapine for three weeks, starting when they were 28 days old. As adults, these rats had “significant deficits of working memory.” They were also “more reactive to handling and had an enhanced response to social novelty.” The Maryland and Lethbridge researchers concluded that “these data suggest that adolescent exposure to olanzapine induces a pattern of long-term behavioral deficits consistent with alterations in dopaminergic function.”
In the second study, the researchers looked at the long-term change in dopamine function in the olanzapine-exposed rats. Four to six months after that early-childhood exposure, the binding activities of dopamine receptors in their “adult” brains were significantly different than normal.
Hundreds of thousands of children in the United States are being medicated today with Zyprexa and other atypical antipsychotics; this study raises the worry that, even if this exposure is for a short period, it might produce permanent deficits.
“Early-life antipsychotic drug exposure can potentially cause long-lasting, functionally significant changes in neural circuitry,” the researchers wrote. “Animal experiments increasingly indicate that exposure to drugs that modulate monaminergic neurotransmission at stages corresponding to human fetal life or early childhood produces long-term behavioral dysfunction.”
Our National Experiment
The widespread medicating of children in the United States is often described by scientists as a grand “experiment,” since the long-term effects of the drugs on normal brain development have not been well studied. Unfortunately, these animal studies suggest that this experiment is not going to turn out well.
December 4, 2010