Interaction of the serotonin transporter-linked polymorphic region and environmental adversity: increased amygdala-hypothalamus connectivity as a potential mechanism linking neural and endocrine hyperreactivity
BACKGROUND: Gene by environment (G×E) interaction between genetic variation in the promoter region of the serotonin transporter gene (serotonin transporter-linked polymorphic region [5-HTTLPR]) and stressful life events (SLEs) has been extensively studied in the context of depression. Recent finding...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
12 March 2012
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| In: |
Biological psychiatry
Year: 2012, Volume: 72, Issue: 1, Pages: 49-56 |
| ISSN: | 1873-2402 |
| DOI: | 10.1016/j.biopsych.2012.01.030 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1016/j.biopsych.2012.01.030
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| Author Notes: | Nina Alexander, Tim Klucken, Georgia Koppe, Roman Osinsky, Bertram Walter, Dieter Vaitl, Gebhard Sammer, Rudolf Stark, and Juergen Hennig |
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| 245 | 1 | 0 | |a Interaction of the serotonin transporter-linked polymorphic region and environmental adversity |b increased amygdala-hypothalamus connectivity as a potential mechanism linking neural and endocrine hyperreactivity |c Nina Alexander, Tim Klucken, Georgia Koppe, Roman Osinsky, Bertram Walter, Dieter Vaitl, Gebhard Sammer, Rudolf Stark, and Juergen Hennig |
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| 520 | |a BACKGROUND: Gene by environment (G×E) interaction between genetic variation in the promoter region of the serotonin transporter gene (serotonin transporter-linked polymorphic region [5-HTTLPR]) and stressful life events (SLEs) has been extensively studied in the context of depression. Recent findings suggest increased neural and endocrine stress sensitivity as a possible mechanism conveying elevated vulnerability to psychopathology. Furthermore, these G×E mediated alterations very likely reflect interrelated biological processes. METHODS: In the present functional magnetic resonance imaging study, amygdala reactivity to fearful stimuli was assessed in healthy male adults (n = 44), who were previously found to differ with regard to endocrine stress reactivity as a function of 5-HTTLPR × SLEs. Furthermore, functional connectivity between the amygdala and the hypothalamus was measured as a potential mechanism linking elevated neural and endocrine responses during stressful/threatening situations. The study sample was carefully preselected regarding 5-HTTLPR genotype and SLEs. RESULTS: We report significant G×E interaction on neural response patterns and functional amygdala-hypothalamus connectivity. Specifically, homozygous carriers of the 5-HTTLPR S' allele with a history of SLEs (S'S'/high SLEs group) displayed elevated bilateral amygdala activation in response to fearful faces. Within the same sample, a comparable G×E interaction effect has previously been demonstrated regarding increased cortisol reactivity, indicating a cross-validation of heightened biological stress sensitivity. Furthermore, S'S'/high SLEs subjects were characterized by an increased functional coupling between the right amygdala and the hypothalamus, thus indicating a potential link between neural and endocrine hyperreactivity. CONCLUSIONS: The present findings contribute to the ongoing debate on 5-HTTLPR × SLEs interaction and are discussed with respect to clinical implications. | ||
| 650 | 4 | |a Adult | |
| 650 | 4 | |a Amygdala | |
| 650 | 4 | |a Brain Mapping | |
| 650 | 4 | |a Facial Expression | |
| 650 | 4 | |a Fear | |
| 650 | 4 | |a Gene-Environment Interaction | |
| 650 | 4 | |a Humans | |
| 650 | 4 | |a Hydrocortisone | |
| 650 | 4 | |a Hypothalamus | |
| 650 | 4 | |a Life Change Events | |
| 650 | 4 | |a Magnetic Resonance Imaging | |
| 650 | 4 | |a Male | |
| 650 | 4 | |a Neural Pathways | |
| 650 | 4 | |a Polymorphism, Genetic | |
| 650 | 4 | |a Reference Values | |
| 650 | 4 | |a Serotonin Plasma Membrane Transport Proteins | |
| 650 | 4 | |a Stress, Psychological | |
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