Neural correlates of self-directed violence: A large-sample resting-state fMRI study from UK Biobank

Suicide remains a leading cause of death worldwide, underscoring the importance of identifying neurobiological markers associated with suicidal behaviors. While nonsuicidal self-directed violence (NSSDV) is an established risk factor for future suicide attempts (SAs), the underlying neural distinctions between these behaviors remain insufficiently understood.

A total of 1,070 participants with a history of self-directed violence (SDV) were stratified into SA (n = 579) and NSSDV (n = 491) groups based on self-reported questionnaires. All data were collected from the UK Biobank between October 2016 and January 2024. Whole-brain connectome across 90 brain regions were analyzed. A general linear regression model was employed to identify significant functional connectivity (FC) correlations with SA. An exploratory analysis examined the correlation between FC and SDV frequency and recency.

Compared to NSSDV, the SA group exhibited decreased FC in the bilateral amygdala and right putamen, alongside increased FC in the right caudate. Higher frequency of SDV was correlated with increased FC between the orbitofrontal cortex (OFC) and occipital regions, whereas individuals reporting SDV within the past 12 months showed trends of decreased FC between the OFC and both the rectus gyrus and temporal lobe.

This large-sample rs-fMRI study highlights distinct FC alterations associated with different dimensions of self-harm. Results implicated that the limbic and reward circuits appear particularly relevant in differentiating SA from NSSDV and in capturing variations tied to SDV frequency and recency. These insights advance our understanding of suicidal behaviors' neurobiological underpinnings and may inform targeted risk stratification.