title: Genetic and early environmental influences on the serotonin system: consequences for brain development and risk for psychopathology.
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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Sainte-Justine Hospital Research Center & University of Montréal, Montréal, Que.; Department of Psychology and Psychiatry, Queen's University, Kingston, Ont.; Department of Psychiatry, McGill University, Montréal, Que.; Department of Psychiatry, University of Montréal, Montréal, Que.
authors.forename: Linda
authors.initials: L
authors.lastname: Booij
authors.affiliation: Sainte-Justine Hospital Research Center & University of Montréal, Montréal, Que.; Departments of Psychology and Pediatrics, University of Montréal, Montréal, Que.; School of Public Health and Population Sciences, University College Dublin, Dublin, Ireland.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Tremblay
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montréal, Que., Canada.
authors.forename: Moshe
authors.initials: M
authors.lastname: Szyf
authors.affiliation: Department of Psychiatry, McGill University, Montréal, Que.
authors.forename: Chawki
authors.initials: C
authors.lastname: Benkelfat
mesh_terms: D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000503:physiopathology*; D004777:Environment; D044127:Epigenesis, Genetic; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D001523:Mental Disorders / Q000503:physiopathology*; D012701:Serotonin / Q000235:genetics* / Q000378:metabolism*
chemical_list: D012701:Serotonin