Altered brain structure and function correlate with non-suicidal self-injury in children and adolescents with transdiagnostic psychiatric disorders.

Non-suicidal self-injury (NSSI) is a prevalent mental problem among children and adolescents, cutting across psychiatric disorders. Studies in specific disorders such as depression and ADHD have revealed associations with alterations in brain regions responsible for reward processing and emotion regulation. However, it remains largely unknown whether such associations are shared among different disorders. Here, we aimed to examine brain structural and functional associations with NSSI in a transdiagnostic psychiatric cohort of children and adolescents. A total of 386 patients (age = 10.72 ± 3.53, range = 5.04 to 21.22) diagnosed primarily with ADHD, autism and generalized anxiety disorder from the Healthy Brain Network study were included. Using linear regression models, we examined brain volumes (N = 386) and functional connectivities (N = 277) associated with NSSI and whether potential alterations could moderate/mediate the links between internalizing/externalizing symptoms and NSSI. We found that increased severity of NSSI was associated with decreased bilateral putamen volumes, and reduced connectivities of the left putamen with bilateral regions of temporoparietal junction and of the right putamen with the left temporoparietal junction, demonstrating the role of putamen in NSSI behavior. Moreover, some of these associations played moderating roles: in patients with lower putamen volumes or weaker functional connectivities, increased internalizing/externalizing symptoms were associated with higher NSSI severity. Our findings suggest that transdiagnostic NSSI is linked to structural alterations and functional dysfunctions in putamen, highlighting that putamen may serve as a neural marker of NSSI and as a potential target for neuromodulation treatments across mental conditions.