Corley Emma, Patlola Saahithh Redddi, Laighneach Aodán, Corvin Aiden, McManus Ross, Kenyon Marcus, Kelly John P, Mckernan Declan P, King Sinead, Hallahan Brian, Mcdonald Colm, Morris Derek W, Donohoe Gary
School of Psychology, University of Galway, Ireland; Centre for Neuroimaging, Cognition, and Genomics (NICOG), University of Galway, Ireland.
Centre for Neuroimaging, Cognition, and Genomics (NICOG), University of Galway, Ireland; Pharmacology & Therapeutics and Galway Neuroscience Centre, University of Galway, Ireland.
Brain Behav Immun. 2024 Jan;115:26-37. doi: 10.1016/j.bbi.2023.09.013. Epub 2023 Sep 23.
Recent studies have reported a negative association between exposure to childhood trauma, including physical neglect, and cognitive functioning in patients with schizophrenia. Childhood trauma has been found to influence immune functioning, which may contribute to the risk of schizophrenia and cognitive symptoms of the disorder. In this study, we aimed to test the hypothesis that physical neglect is associated with cognitive ability, and that this association is mediated by a combined latent measure of inflammatory response, and moderated by higher genetic risk for schizophrenia. The study included 279 Irish participants, comprising 102 patients and 177 healthy participants. Structural equation modelling was used to perform mediation and moderation analyses. Inflammatory response was measured via basal plasma levels of IL-6, TNF-α, and CRP, and cognitive performance was assessed across three domains: full-scale IQ, logical memory, and the emotion recognition task. Genetic variation for schizophrenia was estimated using a genome-wide polygenic score based on genome-wide association study summary statistics. The results showed that inflammatory response mediated the association between physical neglect and all measures of cognitive functioning, and explained considerably more variance than any of the inflammatory markers alone. Furthermore, genetic risk for schizophrenia was observed to moderate the direct pathway between physical neglect and measures of non-social cognitive functioning in both patient and healthy participants. However, genetic risk did not moderate the mediated pathway associated with inflammatory response. Therefore, we conclude that the mediating role of inflammatory response and the moderating role of higher genetic risk may independently influence the association between adverse early life experiences and cognitive function in patients and healthy participants.
近期研究报告称，童年期受创伤（包括身体忽视）与精神分裂症患者的认知功能之间存在负相关。研究发现童年期创伤会影响免疫功能，这可能会增加患精神分裂症的风险以及该疾病的认知症状。在本研究中，我们旨在验证以下假设：身体忽视与认知能力相关，且这种关联由炎症反应的综合潜在指标介导，并受到精神分裂症较高遗传风险的调节。该研究纳入了279名爱尔兰参与者，其中包括102名患者和177名健康参与者。采用结构方程模型进行中介和调节分析。通过白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和C反应蛋白（CRP）的基础血浆水平来测量炎症反应，并从三个领域评估认知表现：全量表智商、逻辑记忆和情绪识别任务。基于全基因组关联研究汇总统计数据，使用全基因组多基因评分来估计精神分裂症的基因变异。结果表明，炎症反应介导了身体忽视与所有认知功能指标之间的关联，并且比任何单一炎症标志物解释的方差都要多得多。此外，在患者和健康参与者中均观察到，精神分裂症的遗传风险调节了身体忽视与非社会认知功能指标之间的直接路径。然而，遗传风险并未调节与炎症反应相关的中介路径。因此，我们得出结论，炎症反应的中介作用和较高遗传风险的调节作用可能独立影响患者和健康参与者早期不良生活经历与认知功能之间的关联。
