Childhood maltreatment and anxiety, depression and self-harm behaviors : A Two-Sample Mendelian Randomization Study

Abstract

Abstract Objective Observational studies have shown associations between childhood maltreatment (CM) and increased risks of Major Depressive Disorder (MDD), Anxiety (ANX), and self-harm and suicidal behaviors. We conducted a Mendelian Randomization study to evaluate the causal effects of these associations. Methods We gathered genetic data from publicly available Genome-Wide Association Studies (GWAS) on childhood maltreatment, MDD, ANX, age of onset for depression, number of depressive episodes, and self-harm and suicidal behaviors. To assess the causal impact of childhood maltreatment on the incidence and symptoms of ANX and MDD, we conducted comprehensive MR analyses and sensitivity analyses using methods such as Inverse Variance Weighted (IVW), MR Egger, Weighted Median (WM), and MR-PRESSO models. The findings were reported as Odds Ratios (ORs) with Confidence Intervals (CIs). Results There was a significant association between childhood maltreatment and the risk of developing MDD (IVW: OR = 2.28, 95% CI = 1.66–3.14, P < 0.001) and ANX (IVW: OR = 1.01, 95% CI = 1-1.02, P = 0.027). Additionally, childhood maltreatment was likely to increase the self-harming behaviors (IVW: OR = 1.06, 95% CI = 1.04–1.08, P < 0.001) and the frequency of depressive episodes (IVW: β = 0.31, 95% CI = 0.17–0.46, P < 0.001), and was associated with an earlier age of onset for depression (IVW: β=-0.17, 95% CI=-0.32 to -0.02, P = 0.025). Conclusion Childhood maltreatment is a potential risk factor for MDD, ANX, and self-harming behaviors. It is associated with the frequency of depressive episodes and an earlier age of onset for depression.