Genetic variants within the dopaminergic system interact to modulate endocrine stress reactivity and recovery

被引：40

作者：

Alexander, Nina ^{[1
]}

Osinsky, Roman ^{[1
]}

Mueller, Eva ^{[1
]}

Schmitz, Anja ^{[2
]}

Guenthert, Sarah ^{[1
]}

Kuepper, Yvonne ^{[1
]}

Hennig, Juergen ^{[1
]}

机构：

[1] Univ Giessen, Ctr Psychobiol & Behav Med, Dept Psychol, D-35394 Giessen, Germany

[2] NIMH, Genet Epidemiol Res Branch, Bethesda, MD 20892 USA

来源：

BEHAVIOURAL BRAIN RESEARCH | 2011年 / 216卷 / 01期

关键词：

COMT val(158)Met; DAT1; VNTR; Gene-gene interaction; HPA-axis; Stress reactivity; Cortisol; CATECHOL-O-METHYLTRANSFERASE; MEDIAL PREFRONTAL CORTEX; PSYCHOLOGICAL STRESS; TRANSPORTER AVAILABILITY; NUCLEUS-ACCUMBENS; CORTICAL DOPAMINE; AVERSIVE STIMULI; MATERNAL-CARE; IN-VIVO; COMT;

D O I：

10.1016/j.bbr.2010.07.003

中图分类号：

B84 [心理学]; C [社会科学总论]; Q98 [人类学];

学科分类号：

03 ; 0303 ; 030303 ; 04 ; 0402 ;

摘要：

Catecholamines modulate endocrine stress reactivity by affecting regulatory influences of extra-hypothalamic brain structures on hypothalamus-pituitary-adrenal (HPA)-axis. Therefore, we aimed to investigate combined effects of functional allelic variations that affect dopamine availability in both cortical (COMTVal(158)Met polymorphism) and subcortical (DAT1 VNTR) brain regions on HPA-axis reactivity to psychosocial stress. By using a standardized laboratory stress task (public speaking) we obtained saliva cortisol samples during stress exposure and an extended recovery period in 100 healthy male adults. We report for the first time significant epistasis between COMT Val(158)Met and DAT1 VNTR on cortisol response patterns. Subjects homozygous for both the Met(158) and the 10-repeat allele of DAT1 VNTR were characterized by markedly elevated cortisol reactivity and impaired stress recovery compared to all other groups. Our results indicate a crucial role of functional genetic variants within the dopaminergic system in the modulation of HPA-axis response patterns and highlight the need to investigate combined effects of specific candidate genes on stress-related endophenotypes. (C) 2010 Elsevier B.V. All rights reserved.

引用

页码：53 / 58

页数：6

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