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11 - The role of serotonin transporter in modeling psychiatric disorders: focus on depression, emotion regulation, and the social brain

Published online by Cambridge University Press:  06 July 2010

By
Klaus-Peter Lesch
Edited by
Allan V. Kalueff  and
Justin L. LaPorte
Allan V. Kalueff
Affiliation:
Georgetown University Medical Center
Justin L. LaPorte
Affiliation:
National Institute of Mental Health
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Summary

ABSTRACT

Depression is an etiologically and clinically heterogeneous syndrome frequently co-occurring in a wide spectrum of psychiatric disorders. Characterized by a wide range of symptoms that reflect alterations in cognitive, emotional, and psychomotor processes, this syndrome is moderately to highly heritable, and caused by interaction of genes and adverse life events. Differentiation of risk-related psychobiological and neuropsychological markers is essential for the dissection of the complex genetic susceptibility to depression and comorbid disorders. A brain serotonin (5-HT) system dysfunction is thought to be involved in the pathogenesis of depression by modulating cognitive dysfunction, stress response, neuroadaptive processes, and resulting pervasive emotional disturbance. A regulatory variation in the gene encoding the 5-HT transporter (5-HTT), the master controller in the fine-tuning of 5-HT signaling, is not only associated with anxiety-related traits, but also modifies the risk of developing disorders of emotion regulation. Yet the neural and molecular mechanisms underlying gene × environment interaction are poorly understood. This paper investigates innate variability of brain 5-HTT function from an interdisciplinary perspective blending behavioral genetics and cognitive neuroscience. Following an appraisal of imaging neural correlates of genomic variation and epigenetic mechanisms as a strategy for psychiatric disorder risk assessment, future challenges for biosocial sciences in the perspective of the complex genetic architecture of emotional behavior and social interaction in non-human primates and humans are defined.

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Experimental Models in Serotonin Transporter Research , pp. 308 - 352
Publisher: Cambridge University Press
Print publication year: 2010

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