Multimodal neuroimaging alterations associated with transdiagnostic non-suicidal self-injury behaviors and suicidal attempts

Background Non-suicidal self-injury (NSSI) and suicide attempts (SA) are critical public health concerns, yet their shared and distinct neurobiological mechanisms remain poorly understood due to diagnostic fragmentation and methodological heterogeneity in previous neuroimaging studies. Methods We conducted a preregistered multimodal meta-analysis using seed-based d mapping (SDM) to synthesize structural magnetic resonance imaging, diffusion tensor imaging, and functional magnetic resonance imaging data across psychiatric disorders. A systematic literature search identified 43 studies comprising 46 datasets (2,097 individuals with self-harm behaviors and 1,809 controls). The analyses included jackknife sensitivity, meta-regression, and subgroup analyses stratified by behavioral phenotype and developmental stage. Results We identified transdiagnostic neural alterations associated with self-harm, including hyperactivity in the left posterior cingulate gyrus (PCG), hypoactivity in the right medial superior frontal gyrus (mSFG), reduced gray matter volume (GMV) in the lingual gyrus, and compromised white matter integrity in the corpus callosum (CC), Brodmann area (BA) 48, and amygdala. Meta-regression revealed three specific brain regions that were negatively associated with age. Subgroup analyses revealed distinct neuropathological mechanisms between the NSSI and SA phenotypes. Furthermore, developmental-stage stratification demonstrated different neuroimaging alteration patterns, with the adult subgroup exhibiting findings more consistent with the main pooled analysis. Conclusion This study provides robust evidence of both convergent and phenotype-specific neural abnormalities underlying self-harm behaviors, offering a transdiagnostic neurobiological framework for early intervention and biomarker development in suicide prevention.