Department of Psychiatry, Parc Taulí Hospital Universitari, I3PT, Universitat Autònoma de Barcelona, Sabadell, Spain; Department of Clinical Sciences, School of Medicine, Universitat de Barcelona, Barcelona, Spain.
Department of Psychiatry, Bellvitge University Hospital, Bellvitge Biomedical Research Institute (IDIBELL), Neurosciences Group-Psychiatry and Mental Health, Barcelona, Spain; Department of Clinical Sciences, School of Medicine, Universitat de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Carlos III Health Institute, Madrid, Spain.
Psychoneuroendocrinology. 2021 Jun;128:105221. doi: 10.1016/j.psyneuen.2021.105221. Epub 2021 Apr 9.
Cognitive impairment has been associated with both childhood adversity and abnormalities of hypothalamic-pituitary-adrenal (HPA) axis function. An interaction exists between the functional polymorphism rs1360780 in the FKBP5 gene and childhood maltreatment, influencing a variety of clinical outcomes. Our goal was to study the relationship between different types of childhood trauma, HPA axis functionality, rs1360780 genotype and cognitive function in 198 healthy individuals who participated in the study. We obtained clinical data, childhood maltreatment scores and neurocognitive performance by clinical assessment; HPA negative feedback was analysed using the dexamethasone suppression test ratio (DSTR) after administration of 0.25 mg of dexamethasone; and the FKBP5 rs1360780 polymorphism was genotyped in DNA obtained from blood samples. The results showed a significant influence of physical neglect on measures of neurocognition as well as an interaction between the DSTR and physical and emotional neglect. Regarding social cognition, a significant association was found with sexual and physical abuse as well as with rs1360780 risk-allele carrier status. Moreover, an interaction between the rs1360780 genotype and the presence of physical abuse was significantly associated with social cognition results. Our results suggest a specific impact of different kinds of childhood maltreatment on measures of neurocognition and social cognition, which might be influenced by HPA axis reactivity and genetic variants in HPA axis-related genes such as FKBP5. Disentangling the relationship between these elements and their influence on cognitive performance might help identify susceptible individuals with higher stress vulnerability and develop preventive interventions.
认知障碍与儿童逆境和下丘脑-垂体-肾上腺（HPA）轴功能异常有关。FKBP5 基因 rs1360780 功能多态性与儿童期虐待相互作用，影响多种临床结局。我们的目标是在 198 名健康参与者中研究不同类型的儿童创伤、HPA 轴功能、rs1360780 基因型与认知功能之间的关系。我们通过临床评估获得临床数据、儿童期虐待评分和神经认知表现；通过给 0.25mg 地塞米松后分析地塞米松抑制试验比值（DSTR）来分析 HPA 负反馈；并从血液样本中提取 DNA 来检测 FKBP5 rs1360780 多态性。结果表明，身体忽视对神经认知测量有显著影响，DSTR 与身体和情感忽视之间存在相互作用。对于社会认知，与性虐待和身体虐待以及 rs1360780 风险等位基因携带者状态有显著相关性。此外，rs1360780 基因型与身体虐待的存在之间的相互作用与社会认知结果显著相关。我们的结果表明，不同类型的儿童虐待对神经认知和社会认知的测量有特定的影响，这可能受到 HPA 轴反应性和 HPA 轴相关基因（如 FKBP5）中遗传变异的影响。阐明这些因素之间的关系及其对认知表现的影响可能有助于识别应激易感性较高的易感个体，并制定预防干预措施。
