Secció de Zoologia i Antropologia Biològica, Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals, Universitat de Barcelona (UB), Avinguda Diagonal 643, 08028 Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain.
Department of Psychology, University of North Carolina at Greensboro, Greensboro, NC 27402-6170, United States; Department of Psychology, University of Illinois at Champaign-Urbana, Champaign, IL 61820, United States.
Psychoneuroendocrinology. 2017 Nov;85:200-209. doi: 10.1016/j.psyneuen.2017.08.024. Epub 2017 Aug 26.
Childhood trauma has been associated with a heightened risk for presenting clinical and non-clinical psychopathology in adulthood. Genes related with the stress response, such as the FK506 binding protein 51 (FKBP5), are plausible candidates moderating the effects of childhood trauma on the emergence of such symptoms later on. The present study aimed to explore the moderating role of FKBP5 genetic variability on the association of different types of childhood trauma with subclinical psychosis, depression and anxiety in a non-clinical sample.
Schizotypy, psychotic-like experiences, depression and anxiety symptoms and childhood trauma were assessed in 808 young adults. Two FKBP5 haplotypic blocks were detected: block 1 (rs3800373 - rs9296158 - rs1360780) and block 2 (rs9470080 - rs4713916). Subjects were classified in two groups according to whether they carried or not the risk haplotype previously described in the literature (block 1: CAT and block 2: TA). Linear regression analyses were used to study (i) the main effects of childhood trauma and FKBP5 haplotype blocks and (ii) their interaction effects on the mentioned forms of psychopathology.
All childhood trauma scales, except sexual abuse, were associated with schizotypy, psychotic-like experiences, depression and anxiety symptoms. None of the analysed symptoms was associated with the main effects of FKBP5 genetic variability. However an interaction effect between block 1 and physical abuse was observed on anxiety, with lower scores in CAT carriers. This effect was driven by SNP 1 and 2. Moreover, an interaction effect between block 2 and physical abuse was identified on the variables tapping depressive and anxiety symptoms. Specifically, non-TA carrier subjects who were exposed to physical abuse were found to be at higher risk for depressive and anxiety symptoms. These effects were driven by SNP 5. No interaction effect was observed for the other variables.
Our data suggest that exposure to childhood physical abuse may increase the risk for sub-clinical depressive and anxiety symptoms depending on FKBP5 genetic variability. Further research is needed to better elucidate the role of FKBP5 on mental health in clinical and non-clinical cohorts.
童年创伤与成年后出现临床和非临床精神病理学的风险增加有关。与应激反应相关的基因，如 FK506 结合蛋白 51（FKBP5），是调节童年创伤对这些症状出现影响的合理候选基因。本研究旨在探讨 FKBP5 基因多态性对非临床样本中不同类型童年创伤与亚临床精神病、抑郁和焦虑之间关联的调节作用。
在 808 名年轻成年人中评估了精神分裂症特质、类精神病体验、抑郁和焦虑症状以及童年创伤。检测到两个 FKBP5 单倍型块：块 1（rs3800373-rs9296158-rs1360780）和块 2（rs9470080-rs4713916）。根据文献中先前描述的风险单倍型（块 1：CAT 和块 2：TA），将受试者分为两组。使用线性回归分析研究了（i）童年创伤和 FKBP5 单倍型块的主要效应，以及（ii）它们对上述精神病理学形式的交互作用。
除了性虐待之外，所有童年创伤量表都与精神分裂症特质、类精神病体验、抑郁和焦虑症状有关。FKBP5 基因变异的主要效应与任何分析症状均无关。然而，在焦虑方面观察到块 1 与躯体虐待之间的交互作用，CAT 携带者的分数较低。这种效应是由 SNP1 和 2 驱动的。此外，还在块 2 与躯体虐待之间确定了对抑郁和焦虑症状有影响的变量的交互作用。具体来说，暴露于躯体虐待的非-TA 携带者被发现患有抑郁和焦虑症状的风险更高。这些影响是由 SNP5 驱动的。在其他变量中未观察到交互作用。
我们的数据表明，暴露于童年期躯体虐待可能会增加 FKBP5 基因多态性亚临床抑郁和焦虑症状的风险。需要进一步的研究来更好地阐明 FKBP5 在临床和非临床队列中的心理健康作用。
