Beyond Depression and Chronic Pain: Toward Understanding the Complex Developmental Pathways to Self-Harm

Abstract

Self-harm is a substantial public health challenge, shaped by a complex interplay of biological, psychological, social, and environmental factors (1,2). Despite substantial progress in psychiatric genetics, the mechanisms linking self-harm to broader dimensions of mental and physical health remain poorly understood. In a recent study published in Biological Psychiatry: Global Open Science , Liu et al. (3) address this question by integrating epidemiological analyses, polygenic risk scores, linkage disequilibrium score regression, Mendelian randomization, genomic structural equation modeling (SEM), and multivariate genome-wide association analyses to investigate the relationships between chronic pain, depression, lifetime self-harm ideation, and self-harm behavior. Their findings demonstrate that depression has a substantially stronger relationship with self-harm compared with chronic pain. Their findings also suggest that the association between chronic pain and self-harm may be mediated, at least in part, by depression, and highlight biological pathways involved in synaptic signaling and neurodevelopment. Building on these findings, we focus on 2 areas that we think will be particularly important for future research: understanding these relationships at a more detailed phenotypic level, going beyond broad diagnostic categories, and examining how they emerge and change across development.