Childhood maltreatment and mental health: causal links to depression, anxiety, non-fatal self-harm, suicide attempts, and PTSD

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