Development passes through sensitive periods, during which plasticity
allows for genetic and environmental factors to exert indelible
influence on the maturation of the organism. In the context of central
nervous system (CNS) development, such sensitive periods shape
the formation of neuro-circuits that mediate, regulate, and control
behavior. This general mechanism allows for development to be guided by
both the genetic blueprint, as well as the environmental context. While
allowing for adaptation, such sensitive periods are also windows of
vulnerability during which external and internal factors can confer risk
to brain
disorders by derailing adaptive developmental programs. Our group has
been particularly interested in developmental periods that are sensitive
to serotonin
(5-HT) signaling, and impact behavior and cognition relevant to
psychiatry. Specifically, we review a 5-HT-sensitive period that impacts
fronto-limbic system development, resulting in cognitive, anxiety, and
depression-related behaviors. We discuss preclinical data to establish
biological plausibility and mechanistic insights.
We also summarize epidemiological findings that underscore the
potential public health implications resulting from the current practice
of prescribing 5-HT reuptake
inhibiting antidepressants during pregnancy. These medications enter
the fetal circulation, likely perturb 5-HT signaling in the brain, and may be affecting circuit maturation in ways that parallel our findings in the developing rodent brain.
More research is needed to better disambiguate the dual effects of
maternal symptoms on fetal and child development from the effects of
5-HT reuptake inhibitors on clinical outcomes in the offspring. Birth Defects Research 109:924-932, 2017.