Zhang Zheng, Jiang Chenggang, Wang Xinglian, Qiu Haitang, Li Jiazheng, Wang Yating, Luo Qinghua, Ju Yuanzhi
Department of Psychiatry, Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Department of Sleep and Psychology, Chongqing Health Center for Women and Children, Chongqing, People's Republic of China.
Eur J Psychotraumatol. 2025 Dec;16(1):2480884. doi: 10.1080/20008066.2025.2480884. Epub 2025 May 14.
This study aims to elucidate the causal relationship between childhood maltreatment (CM) and subsequent mental health outcomes, including major depressive disorder (MDD), anxiety (ANX), post-traumatic stress disorder (PTSD), suicide attempts, and non-fatal self-harm. Utilising Mendelian Randomisation (MR) and genome-wide association studies (GWAS) data from individuals of European descent, this research applies a rigorous analytical methodology to large-scale datasets, overcoming the confounding variables inherent in previous observational studies. Genetic data were obtained from publicly available GWAS on individuals of European ancestry, focusing on Childhood Maltreatment (CM), Major Depressive Disorder (MDD), Anxiety (ANX), Post-Traumatic Stress Disorder (PTSD), Age at First Episode of Depression, Number of Depression Episodes, Non-fatal self-harm, and Suicide Attempts. Mendelian Randomisation (MR) analyses were conducted to investigate the causal impact of CM on these outcomes. Sensitivity analyses included IVW, MR Egger, WM, and MR-PRESSO. FDR corrections were applied to account for multiple testing. Results were presented as odds ratios (ORs) with confidence intervals (CIs). Significant associations were identified between CM and the likelihood of developing MDD (IVW: = 2.28, 95% = 1.66-3.14, < .001), ANX (IVW: = 1.01, 95% = 1.00-1.02, =.032), and PTSD (IVW: = 2.29, 95% = 1.43-3.67, =.001). CM was also linked to increased non-fatal self-harm (IVW: = 1.06, 95% = 1.04-1.08, <.001), higher frequency of depressive episodes (IVW: =0.31, 95% = 0.17-0.46, <.001), and earlier onset of depression (IVW: =-0.17, 95% = -0.32 to - 0.02, =.033). No significant association was found between CM and suicide attempts (IVW: = 1.09, 95% = 0.81-1.45, =.573). This study provides robust evidence that CM is a significant causal factor for MDD, ANX, PTSD, and non-fatal self-harming behaviours. It is associated with a higher frequency of depressive episodes and earlier onset of depression. These findings highlight the need for early intervention and targeted prevention strategies to address the long-lasting psychological impacts of CM.
本研究旨在阐明童年期虐待（CM）与后续心理健康结局之间的因果关系，这些结局包括重度抑郁症（MDD）、焦虑症（ANX）、创伤后应激障碍（PTSD）、自杀未遂和非致命性自我伤害。本研究利用来自欧洲血统个体的孟德尔随机化（MR）和全基因组关联研究（GWAS）数据，将严谨的分析方法应用于大规模数据集，克服了以往观察性研究中固有的混杂变量。遗传数据来自公开的欧洲血统个体GWAS，重点关注童年期虐待（CM）、重度抑郁症（MDD）、焦虑症（ANX）、创伤后应激障碍（PTSD）、首次抑郁发作年龄、抑郁发作次数、非致命性自我伤害和自杀未遂。进行孟德尔随机化（MR）分析以研究CM对这些结局的因果影响。敏感性分析包括逆方差加权法（IVW）、MR-Egger回归、加权中位数法（WM）和MR-PRESSO检验。采用错误发现率（FDR）校正来处理多重检验问题。结果以比值比（OR）和置信区间（CI）表示。研究发现CM与发生MDD的可能性之间存在显著关联（IVW： = 2.28，95% = 1.66 - 3.14， <.001）、与ANX之间存在显著关联（IVW： = 1.01，95% = 1.00 - 1.02， = 0.032）以及与PTSD之间存在显著关联（IVW： = 2.29，95% = 1.43 - 3.67， = 0.001）。CM还与非致命性自我伤害增加有关（IVW： = 1.06，95% = 1.04 - 1.08， <.001）、与抑郁发作频率更高有关（IVW： = 0.31，95% = 0.17 - 0.46， <.001）以及与抑郁症更早发病有关（IVW： = - 0.17，95% = - 0.32至 - 0.02， = 0.033）。未发现CM与自杀未遂之间存在显著关联（IVW： = 1.09，95% = 0.81 - 1.45， = 0.573）。本研究提供了有力证据，表明CM是MDD、ANX、PTSD和非致命性自我伤害行为的重要因果因素。它与更高的抑郁发作频率和更早的抑郁症发病有关。这些发现凸显了针对CM的长期心理影响进行早期干预和针对性预防策略的必要性。
