Jabbi M, Korf J, Kema I P, Hartman C, van der Pompe G, Minderaa R B, Ormel J, den Boer J A
Department of Psychiatry, University Medical Centre Groningen, Groningen, The Netherlands.
Mol Psychiatry. 2007 May;12(5):483-90. doi: 10.1038/sj.mp.4001975. Epub 2007 Mar 6.
Highly prevalent stress-related disorders such as major depression (MD) are characterised by a dysregulation of the neuroendocrine system. Although heritability for these disorders is high, the role of genes in the underlying pathophysiology is poorly understood. Here, we show that polymorphic variations in genes coding for serotonin transporter (5-HTT), catechol-O-methyl transferase (COMT) and monoamine oxidase A (MAOA) as well as sex differences influence the regulation of hypothalamic-pituitary-adrenal (HPA)-axis response to acute psychological and endocrine challenges. In our sample, the effects of COMT on the release of adrenocorticotrophin hormone (ACTH) depend on the presence of the low-expression MAOA variant in the same individual. By including individuals varying in their degree of susceptibility to MD, we showed evidence of interactions between 5-HTT and MD susceptibility in baseline cortisol, and between MAOA and MD susceptibility in baseline ACTH measures, indicating a role for these genotypes in stable-state endocrine regulation. Collectively, these results indicate that the simultaneous investigation of multiple monoaminergic genes in interaction with gender have to be measured to understand the endocrine regulation of stress. These findings point towards a genetic susceptibility to stress-related disorders.
高度流行的应激相关疾病，如重度抑郁症（MD），其特征是神经内分泌系统失调。尽管这些疾病的遗传度很高，但基因在潜在病理生理学中的作用仍知之甚少。在这里，我们表明，编码5-羟色胺转运体（5-HTT）、儿茶酚-O-甲基转移酶（COMT）和单胺氧化酶A（MAOA）的基因多态性变异以及性别差异会影响下丘脑-垂体-肾上腺（HPA）轴对急性心理和内分泌挑战的反应调节。在我们的样本中，COMT对促肾上腺皮质激素（ACTH）释放的影响取决于同一个体中低表达MAOA变体的存在。通过纳入对MD易感性程度不同的个体，我们发现了5-HTT与基线皮质醇水平下的MD易感性之间以及MAOA与基线ACTH测量值下的MD易感性之间存在相互作用的证据，表明这些基因型在稳态内分泌调节中发挥作用。总体而言，这些结果表明，必须同时研究多个单胺能基因与性别的相互作用，以了解应激的内分泌调节。这些发现表明存在与应激相关疾病的遗传易感性。
