Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital, LMU Munich, Nußbaumstr. 5A, 80336 Munich, Germany.
Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital, LMU Munich, Nußbaumstr. 5A, 80336 Munich, Germany.
Psychoneuroendocrinology. 2019 Aug;106:28-37. doi: 10.1016/j.psyneuen.2019.03.025. Epub 2019 Mar 27.
Major Depression (MD) results from a complex interplay between environmental stressors and biological factors. Previous studies in adults have shown that adverse life events interact with genetic variation in FKBP5, a gene implicated in the stress-response system, to predict depressive symptoms and MD. This is the first study to investigate interactions between FKBP5 variants and a range of environmental stressors in adolescents with a clinical diagnosis of MD.
148 male and female adolescents with MD and 143 typically developing (TD) controls (13-18 years) were included in the present study. For self-reported environmental stressors, subjective severity was assessed to allow a classification of these factors as mild, moderate and severe. Sociodemographic stressors were assessed via parental-report.
With a heightened number of sociodemographic, moderate and total number of stressors, participants carrying at least one copy of the FKBP5 CATT haplotype or at least one minor allele of various FKBP5 SNPs had the highest risk for being in the MD group. No genetic main effects were found. Sociodemographic stressors as well as self-reported mild, moderate, and severe stressors were more common in depressed than in TD adolescents.
This is the first study to show interactions between genetic variation in FKBP5 and environmental stressors in a sample of clinically depressed adolescents. The current study provides important starting-points for preventive efforts and highlights the need for a fine-grained analysis of different forms and severities of environmental stressors and their interplay with genetic variation for understanding the complex etiology of (youth) MD.
重度抑郁症（MD）是环境压力源和生物因素复杂相互作用的结果。先前的成人研究表明，不良生活事件与 FKBP5 基因中的遗传变异相互作用，FKBP5 基因与应激反应系统有关，可预测抑郁症状和 MD。这是第一项研究调查了 MD 临床诊断的青少年中 FKBP5 变体与一系列环境压力源之间的相互作用。
本研究纳入了 148 名 MD 男性和女性青少年和 143 名典型发育（TD）对照者（13-18 岁）。对于自我报告的环境压力源，评估了主观严重程度，以便将这些因素分类为轻度、中度和重度。通过父母报告评估社会人口统计学压力源。
随着社会人口统计学压力源、中度压力源和总压力源数量的增加，携带至少一个 FKBP5 CATT 单倍型拷贝或至少一个 FKBP5 SNP 各种 minor 等位基因的参与者患 MD 的风险最高。未发现遗传主效应。与 TD 青少年相比，抑郁青少年中更常见社会人口统计学压力源以及自我报告的轻度、中度和重度压力源。
这是第一项在临床抑郁青少年样本中显示 FKBP5 基因遗传变异与环境压力源相互作用的研究。本研究为预防措施提供了重要的起点，并强调需要对不同形式和严重程度的环境压力源及其与遗传变异的相互作用进行精细分析，以了解（青少年）MD 的复杂病因。
