Genetic and Early Environmental Influences on the Serotonin System: Consequences for Brain Development and Risk for Psychopathology

Overview

Journal J Psychiatry Neurosci

Specialty Psychiatry

Date 2014 Oct 7

PMID 25285876

Citations 49

Authors

Linda Booij

Richard E Tremblay

Moshe Szyf

Chawki Benkelfat

Affiliations

Soon will be listed here.

Abstract

Background: Despite more than 60 years of research in the role of serotonin (5-HT) in psychopathology, many questions still remain. From a developmental perspective, studies have provided more insight into how 5-HT dysfunctions acquired in utero or early in life may modulate brain development. This paper discusses the relevance of the developmental role of 5-HT for the understanding of psychopathology. We review developmental milestones of the 5-HT system, how genetic and environmental 5-HT disturbances could affect brain development and the potential role of DNA methylation in 5-HT genes for brain development.

Methods: Studies were identified using common databases (e.g., PubMed, Google Scholar) and reference lists.

Results: Despite the widely supported view that the 5-HT system matures in early life, different 5-HT receptors, proteins and enzymes have different developmental patterns, and development is brain region-specific. A disruption in 5-HT homeostasis during development may lead to structural and functional changes in brain circuits that modulate emotional stress responses, including subcortical limbic and (pre)frontal areas. This may result in a predisposition to psychopathology. DNA methylation might be one of the underlying physiologic mechanisms.

Limitations: There is a need for prospective studies. The impact of stressors during adolescence on the 5-HT system is understudied. Questions regarding efficacy of drugs acting on 5-HT still remain.

Conclusion: A multidisciplinary and longitudinal approach in designing studies on the role of 5-HT in psychopathology might help to bring us closer to the understanding of the role of 5-HT in psychopathology.

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