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Updated: Apr 23, 2026

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Published on: July 12, 2024
Genetic and early environmental influences on the serotonin system: consequences for brain development and risk for
Linda Booij1, Richard E Tremblay2, Moshe Szyf3
1Sainte-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.
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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