Interaction of the Serotonin Transporter-Linked Polymorphic Region and Environmental Adversity: Increased Amygdala-Hypothalamus Connectivity as a Potential Mechanism Linking Neural and Endocrine Hyperreactivity

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• 作者：Nina Alexander^a ; ^f ; ^{alexander@biopsych.tu-dresden.de} ; Tim Klucken^b ; Georgia Koppe^c ; ^d ; Roman Osinsky^e ; Bertram Walter^b ; Dieter Vaitl^b ; Gebhard Sammer^c ; Rudolf Stark^b ; Juergen Hennig^f
• 关键词：Amygdala ; functional connectivity ; gene by environment interaction ; 5-HTTLPR ; stress reactivity ; stressful life events
• 刊名：Biological Psychiatry
• 出版年：2012
• 期刊代码：34_00063223
• 类别：med
• 出版时间：1 July, 2012
• 卷：72
• 期：1
• 页码：49-56
• 文件大小：1390 K

摘要

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Background

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