# Structural-functional connectivity decoupling reveals neural differences associated with subtypes of nonsuicidal self-injury among female depressive adolescents

## TL;DR

This study finds brain connectivity differences between female adolescents with depression who do and do not meet criteria for nonsuicidal self-injury, suggesting potential neural markers for subtyping and intervention.

## Contribution

The study introduces structural-functional connectivity (SC-FC) coupling as a novel neural marker to distinguish subtypes of nonsuicidal self-injury in depressed female adolescents.

## Key findings

- The NSSI+ group showed distinct SC-FC coupling in task-positive network regions compared to the NSSI- group.
- The NSSI+ group had widespread coupling abnormalities compared to healthy controls, while the NSSI- group showed fewer differences.
- Decoupling in the right subgenual anterior cingulate correlated with clinical features in the NSSI- group.

## Abstract

Nonsuicidal self-injury (NSSI) is a complex behavior prevalent among adolescents, particularly females and those with depression. The DSM-5 introduced recommended diagnostic criteria for NSSI, yet many adolescents engaging in NSSI do not meet these standards. The neurobiological distinctions between adolescents with NSSI who fulfill the DSM-5 criteria (NSSI+) and those who do not (NSSI-) remain unclear.

Sixty-three female depressive adolescents (40 NSSI+, 23 NSSI-) and 35 healthy controls (HCs) were included and underwent resting-state functional magnetic resonance imaging, diffusion tensor imaging and high-resolution T1-weighted imaging. We explored differences in brain structure-function interactions by applying structural-functional connectivity (SC-FC) coupling analysis using multimodal neuroimaging data. Partial Spearman’s correlation analyses were used to identify association between SC-FC coupling and clinical features.

The NSSI+ group had notably distinct SC-FC coupling in task-positive network regions including decreased SC-FC coupling (greater decoupling) in the left dorsolateral superior frontal gyrus and increased coupling in the bilateral medial precuneus and right opercular inferior frontal gyrus, as compared to the NSSI- group. Moreover, the NSSI+ group displayed widespread coupling abnormalities across multiple networks compared to the HC group, while the NSSI- group only differed in the left dorsolateral superior frontal gyrus. Correlational analyses linked decoupling indices to several clinical features, particularly in the right subgenual anterior cingulate among the NSSI- participants.

These findings indicate that SC-FC coupling patterns distinguish NSSI subtypes in depressed female adolescents, with more severe NSSI associated with altered coupling in prefrontal, precuneus, and inferior frontal regions involved in executive control and attentional processing. The right subgenual anterior cingulate cortex—showing multiple clinical correlations—emerges as a potential target for early intervention of NSSI behavior. These findings highlight the utility of SC-FC coupling as a neural marker for NSSI subtyping and intervention planning.