Uric acid metabolism and brain dysfunction linking childhood maltreatment to self-harm in adolescents with mood...

Childhood maltreatment (CM) elevates self-harm behavior (SHB) risk, potentially through uric acid (UA) dysregulation and UA-mediated neural dysfunction. Targeting these mechanisms may offer valuable insights into preventive strategies.

This study analyzed 540 adolescent inpatients (12-18 years, 74.6 % female) with mood disorders and major depressive episodes, stratified into SHB (N = 397) and NSHB (N = 143) groups. Multimodal assessments incorporated clinical evaluations, serum UA quantification, and resting-state functional magnetic resonance imaging (rs-fMRI) with mean amplitude of low-frequency fluctuations (mALFF) analysis. Analyses encompassed between-group comparisons, logistic regression, and structural equation modeling (SEM) to identify SHB pathways.

Stepwise regression identified elevated serum UA as a protective factor against SHB (β = -0.011, P < 0.001; OR = 0.989, 95 %CI: 0.984-0.994). Significant risk factors included: elevated HAMA (β = 0.089, P < 0.01; OR = 1.094, 95 %CI: 1.025-1.166), higher CTQ emotional abuse (β = 0.142, P < 0.001; OR = 1.153, 95 %CI: 1.059-1.255), and reduced ALFF in bilateral middle temporal gyri (left: β = -3.226, P < 0.01; OR = 0.040, P < 0.01, 95 %CI: 0.004-0.399; right: β = -3.008, P < 0.01; OR = 0.049, P < 0.01, 95 %CI: 0.007-0.352). Critically, SEM revealed that CM indirectly increased SHB risk through a sequential pathway: CM led to UA dysregulation, impairing spontaneous activity within the middle temporal gyri, thereby elevating SHB risk (β = 0.020, P_corrected < 0.05).

Our findings reveal that childhood maltreatment elevates SHB risk via UA-linked metabolic dysregulation and middle temporal gyri hypoactivity, highlighting purine metabolism and temporal circuits as promising targets for precision interventions.