Abstract
Background: 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.Methods: 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).Results: Significant associations were identified between CM and the likelihood of developing MDD (IVW: OR = 2.28, 95% CI = 1.66-3.14, P(FDR )< .001), ANX (IVW: OR = 1.01, 95% CI = 1.00-1.02, P(FDR) =.032), and PTSD (IVW: OR = 2.29, 95% CI = 1.43-3.67, P(FDR) =.001). CM was also linked to increased non-fatal self-harm (IVW: OR = 1.06, 95% CI = 1.04-1.08, P(FDR) <.001), higher frequency of depressive episodes (IVW: β=0.31, 95% CI = 0.17-0.46, P(FDR) <.001), and earlier onset of depression (IVW: β=-0.17, 95% CI = -0.32 to - 0.02, P(FDR) =.033). No significant association was found between CM and suicide attempts (IVW: OR = 1.09, 95% CI = 0.81-1.45, P(FDR) =.573).Conclusion: 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.