The serotonin transporter gene and functional and pathological adaptation to environmental variation across the life span |
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Authors: | Judith R. Homberg Daniel L.A. van den Hove |
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Affiliation: | 1. Donders Institute for Brain, Cognition, and Behavior, Centre for Neuroscience, Dept. of Cognitive Neuroscience, Radboud University Nijmegen Medical Centre, Geert Grooteplein 21, 6525 GA Nijmegen, The Netherlands;2. Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Universiteitssingel 40, 6200 MD Maastricht, The Netherlands;3. Institute of Molecular Psychiatry, Laboratory of Translational Neuroscience, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Fuechsleinstrasse 15, 97080 Wuerzburg, Germany |
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Abstract: | In analogy with the accepted view that behaviour is shaped by gene × environment (G × E) interactions, G × E studies are exponentially increasing in the field of psychiatry. Whereas research was primarily driven by the premature view that negative environmental stimuli can trigger psychopathology in those subjects that are genetically predisposed, a closer look at the available data shows that G × E interactions are much more complex than initially thought. Here, we discuss G × E studies focussing on serotonin transporter (5-HTT, SERT, SLC6A4) gene variation in humans, monkeys, and rodents. Recent studies, across species, confirm the theorized ‘for-better-and-for-worse’ effect of low activity serotonin transporter genotypes. In addition, while 5-HTT × E interactions were thought to take place in early life, recent evidence illustrates that these interactions are also manifested in adulthood. Therefore, we discuss data based on 5-HTT × E interactions, and propose a model in which predictive adaptive responses (PARs), as shaped by early life 5-HTT × E interactions, shape responses to environmental challenges in later life, i.e. reflecting 5-HTT × E × E interactions. |
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Keywords: | 5-HT, serotonin 5-HTT, serotonin transporter 5-HTTLPR, serotonin transporter linked polymorphic region 5-HTT&minus /&minus , serotonin transporter knockout ACTH, adrenocorticotrophin-releasing hormone AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid BDNF, brain-derived neurotrophic factor BOLD, blood oxygen level dependent CpG, cytosine&ndash phosphate&ndash guanosine CRF, corticotrophin-releasing factor CSF, cerebrospinal fluid GABA-A, gamma-aminobutyric acid-A FDG, [18F]fluoro-2-deoxy-d-glucose G × E, gene × environment G × E × E, gene × environment × environment GR, glucocorticoid receptor HPA-axis, hypothalamus&ndash pituitary&ndash adrenal axis L, long allele PAR, predictive adaptive responses PTSD, post-traumatic stress disorder PVN, paraventricular nucleus REM, rapid eye movement SERT, serotonin transporter (rodent) SLC6A4, serotonin transporter gene (human) S, short allele |
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