Genetic and early environmental influences on the serotonin system: Consequences for brain development and risk for psychopathology

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 psycho­ pathology. 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 prospect­ ive 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 psycho­ pathology might help to bring us closer to the understanding of the role of 5-ht in psychopathology. © 2015 8872147 canada inc. or its licensors.