HPA Axis Genes, and Their Interaction with Childhood Maltreatment, are Related to Cortisol Levels and Stress-Related Phenotypes
HPA Axis Genes, and Their Interaction with Childhood Maltreatment, are Related to Cortisol Levels and Stress-Related Phenotypes
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DOI：
10.1038/npp.2017.118
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发表时间：
2017-11-01
影响因子：
7.6
通讯作者：
Penninx, Brenda W. J. H.
中科院分区：
文献类型：
--
作者：
Gerritsen, Lotte;Milaneschi, Yuri;Penninx, Brenda W. J. H.
应激反应受下丘脑-垂体-肾上腺（HPA）轴控制，适应不良应激反应与应激相关疾病（如重度抑郁症（MDD））的发生和维持有关。在HPA轴调节中发挥作用的基因可能有助于相关神经生物学底物和应激相关疾病之间的关系。因此，我们对2014例受试者中参与HPA轴调节的30个先验文献基因进行了全基因分析（34%男性;平均年龄：42.5岁）研究MDD终生诊断、皮质醇觉醒反应和地塞米松抑制试验（DST）水平之间的关系（子样本N = 1472）和海马和杏仁核体积（3 T MR图像;子样本N = 225）。此外，基因的儿童虐待（CM）的相互作用进行了研究。发现地塞米松抑制（CYP 11 A1、CYP 17 A1、POU 1F 1、AKR 1D 1）、海马体积（CYP 17 A1、CYP 11 A1、HSD 3B 2、PROP 1、AVPRA 1、SRD 5A 1）、杏仁核体积（POMC、CRH、HSD 3B 2）和终生MDD诊断（FKBP 5和CRH）的全基因显著性结果，所有排列p值
Stress responses are controlled by the hypothalamus pituitary adrenal (HPA)-axis and maladaptive stress responses are associated with the onset and maintenance of stress-related disorders such as major depressive disorder (MDD). Genes that play a role in the HPA-axis regulation may likely contribute to the relation between relevant neurobiological substrates and stress-related disorders. Therefore, we performed gene-wide analyses for 30 a priori literature-based genes involved in HPA-axis regulation in 2014 subjects (34% male; mean age: 42.5) to study the relations with lifetime MDD diagnosis, cortisol awakening response, and dexamethasone suppression test (DST) levels (subsample N = 1472) and hippocampal and amygdala volume (3T MR images; subsample N = 225). Additionally, gene by childhood maltreatment (CM) interactions were investigated. Gene-wide significant results were found for dexamethasone suppression (CYP11A1, CYP17A1, POU1F1, AKR1D1), hippocampal volume (CYP17A1, CYP11A1, HSD3B2, PROP1, AVPRA1, SRD5A1), amygdala volume (POMC, CRH, HSD3B2), and lifetime MDD diagnosis (FKBP5 and CRH), all permutation p-values