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6720660 
Journal Article 
Review 
Genetic and early environmental influences on the serotonin system: consequences for brain development and risk for psychopathology 
Booij, L; Tremblay, RE; Szyf, M; Benkelfat, C 
2015 
Yes 
Journal of Psychiatry and Neuroscience : JPN
ISSN: 1180-4882
EISSN: 1488-2434 
40 
1 
5-18 
English 
25285876 
WOS:000347545500004 
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.