Linda Booij1, Richard E Tremblay2, Moshe Szyf3, Chawki Benkelfat4. 1. 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. 2. 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. 3. Department of Pharmacology and Therapeutics, McGill University, Montréal, Que., Canada. 4. Department of Psychiatry, McGill University, Montréal, Que.
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.
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.
Authors: Francine Côté; Cécile Fligny; Elisa Bayard; Jean-Marie Launay; Michael D Gershon; Jacques Mallet; Guilan Vodjdani Journal: Proc Natl Acad Sci U S A Date: 2006-12-20 Impact factor: 11.205
Authors: Sylvana M Côté; Michel Boivin; Daniel S Nagin; Christa Japel; Qian Xu; Mark Zoccolillo; Marianne Junger; Richard E Tremblay Journal: Arch Gen Psychiatry Date: 2007-11
Authors: Natalia Alenina; Dana Kikic; Mihail Todiras; Valentina Mosienko; Fatimunnisa Qadri; Ralph Plehm; Philipp Boyé; Larissa Vilianovitch; Reinhard Sohr; Katja Tenner; Heide Hörtnagl; Michael Bader Journal: Proc Natl Acad Sci U S A Date: 2009-06-11 Impact factor: 11.205
Authors: I Ouellet-Morin; C C Y Wong; A Danese; C M Pariante; A S Papadopoulos; J Mill; L Arseneault Journal: Psychol Med Date: 2012-12-10 Impact factor: 7.723
Authors: Elizabeth T C Lippard; Carolyn M Mazure; Jennifer A Y Johnston; Linda Spencer; Judah Weathers; Brian Pittman; Fei Wang; Hilary P Blumberg Journal: J Neurosci Res Date: 2017-01-02 Impact factor: 4.164
Authors: Stephanie H Parade; Andrew M Novick; Justin Parent; Ronald Seifer; Samantha J Klaver; Carmen J Marsit; Asi Polly Gobin; Bao-Zhu Yang; Audrey R Tyrka Journal: Dev Psychopathol Date: 2017-12