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 development, such sensitive periods shape the formation of neurocircuits 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 vulnerability windows during which external and internal factors can confer risk to disorders by derailing otherwise resilient developmental programs. Here we review developmental periods that are sensitive to monoamine signaling and impact adult behaviors of relevance to psychiatry. Specifically, we review (1) a serotonin-sensitive period that impacts sensory system development, (2) a serotonin-sensitive period that impacts cognition, anxiety- and depression related behaviors, and (3) a dopamine- and serotonin-sensitive period affecting aggression, impulsivity and behavioral response to psychostimulants. We discuss preclinical data to provide mechanistic insight, as well as epidemiological and clinical data to point out translational relevance. The field of translational developmental neuroscience has progressed exponentially providing solid conceptual advances and unprecedented mechanistic insight. With such knowledge at hand and important methodological innovation ongoing, the field is poised for breakthroughs elucidating the developmental origins of neuropsychiatric disorders, and thus understanding pathophysiology. Such knowledge of sensitive periods that determine the developmental trajectory of complex behaviors is a necessary step towards improving prevention and treatment approaches for neuropsychiatric disorders.

The available data demonstrate the existence of sensitive periods that influence life-long vulnerability to anxiety, depression, aggression, and substance abuse. Such sensitive periods have been most extensively characterized for sensory systems (eg, visual cortex), but conceptually similar principles apply to the development and organization of brain circuitry that mediate the more complex behaviors described here. Specifically, we have reviewed three sensitive periods during which transiently altered monoamine signaling carries long-lasting consequences on adult brain function. Respective findings lead to the following three working hypotheses:

1. Any manipulation, which increases 5-HT signaling during development (P0–P4 in mice), will impair somatosensory cortex maturation and lateral geniculate nucleus/superior colliculus topography.

2. Any manipulation, which increases 5-HT signaling during development (P2–P11 in mice), will increase adult anxiety/depression-like behavior and impair cognition.

3. Any manipulation, which increases DA signaling during development (P22–P41 in mice), will increase adult aggression and behavioral response to stimulants, whereas any manipulation that increases 5-HT signaling during that same period will decrease adult aggression and behavioral stimulant sensitivity.

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Monoamine-Sensitive Developmental Periods Impacting Adult Emotional and Cognitive Behaviors

Neuropsychopharmacology REVIEWS (2015) 40, 88–112 & 2015

by Deepika Suri, et al., Department of Psychiatry, Columbia University, New York, NY, USA; 2 New York State Psychiatric Institute, New York, NY, USA