Jabbi Mbemba, Kema Ido P, van der Pompe Gieta, te Meerman Gerard J, Ormel Johan, den Boer Johan A
Departments of Psychiatry, University Medical Center Groningen, UMCG dBCN NeuroImaging Center, Groningen, Netherlands.
Psychiatr Genet. 2007 Jun;17(3):183-93. doi: 10.1097/YPG.0b013e32808374df.
The stress response is related to both physiological and psychological factors and is strongly marked by a neuroendocrine component. Genetic factors are believed to underlie individual differences in the degree of stress resilience and thereby contribute in determining susceptibility to stress-related pathologies like major depressive disorder (MDD). Little, however, is known about the genetic influence on the endocrine and behavioural stress response in relation to MDD.
Here, we sought to examine the effects of the catechol-o-methyltransferase polymorphism on psychological stress in three groups of individuals with different degrees of susceptibility to MDD (i.e. healthy controls, healthy high risk probands to MDD and those suffering from MDD). This genotype is involved in the metabolism of catecholamines (dopamine, norepinephrine and epinephrine).
Allelic variations of this polymorphism were found to influence the degree of subjective stress experience and plasma epinephrine stress response. Interactions between catechol-o-methyltransferase polymorphism and diagnostic group in measures of plasma epinephrine, cortisol and subjective responses to psychological stress were also found, with the influence of the different alleles on these measures differing between healthy controls relative to MDD patients and high risk probands.
These observations support a possible role for catechol-o-methyltransferase polymorphism in the endocrine and subjective response to psychological stress and thus may qualify as a possible candidate gene involved in the pathogenesis of MDD.
应激反应与生理和心理因素均相关，且具有显著的神经内分泌成分。遗传因素被认为是个体应激恢复能力差异的基础，从而有助于确定对诸如重度抑郁症（MDD）等应激相关疾病的易感性。然而，关于遗传因素对与MDD相关的内分泌和行为应激反应的影响，人们知之甚少。
在此，我们试图研究儿茶酚-O-甲基转移酶多态性对三组对MDD易感性不同的个体（即健康对照者、MDD健康高危先证者和MDD患者）心理应激的影响。该基因型参与儿茶酚胺（多巴胺、去甲肾上腺素和肾上腺素）的代谢。
发现该多态性的等位基因变异会影响主观应激体验程度和血浆肾上腺素应激反应。在血浆肾上腺素、皮质醇以及对心理应激的主观反应测量中，还发现了儿茶酚-O-甲基转移酶多态性与诊断组之间的相互作用，不同等位基因对这些测量指标之影响在健康对照者相对于MDD患者及高危先证者之间存在差异。
这些观察结果支持儿茶酚-O-甲基转移酶多态性在心理应激的内分泌和主观反应中可能发挥的作用，因此可能符合作为参与MDD发病机制的一个候选基因。
