Journal article

Publication year: 2012

Pages: 49-56

Journal: Biological Psychiatry

Volume number: 72

Issue number: 1

ISSN: 0006-3223

eISSN: 1873-2402

DOI Link: https://doi.org/10.1016/j.biopsych.2012.01.030

Publisher: Elsevier

Abstract: 

Background: Gene by environment (G x 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 x 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 x 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 x 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 x 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 x SLEs interaction and are discussed with respect to clinical implications.

Harvard Citation style: Alexander, N., Klucken, T., Koppe, G., Osinsky, R., Walter, B., Vaitl, D., et al. (2012) Interaction of the Serotonin Transporter-Linked Polymorphic Region and Environmental Adversity: Increased Amygdala-Hypothalamus Connectivity as a Potential Mechanism Linking Neural and Endocrine Hyperreactivity, Biological Psychiatry, 72(1), pp. 49-56. https://doi.org/10.1016/j.biopsych.2012.01.030

APA Citation style: Alexander, N., Klucken, T., Koppe, G., Osinsky, R., Walter, B., Vaitl, D., Sammer, G., Stark, R., & Hennig, J. (2012). Interaction of the Serotonin Transporter-Linked Polymorphic Region and Environmental Adversity: Increased Amygdala-Hypothalamus Connectivity as a Potential Mechanism Linking Neural and Endocrine Hyperreactivity. Biological Psychiatry. 72(1), 49-56. https://doi.org/10.1016/j.biopsych.2012.01.030