Brain functional alterations link serum lipid profiles to self-harm behavior in adolescents with mood disorders

Emerging evidence links serum lipid alterations to self-harm behavior (SHB), but underlying neurobiological pathways remain insufficiently investigated, particularly in adolescents with mood disorders (MD).

We recruited 407 adolescent inpatients (12-18 years) with MD experiencing major depressive episodes, divided into SHB (N = 297) and non-SHB (NSHB, N = 110) groups. SHB-associated clinical, lipid, and mean amplitude of low-frequency fluctuations (mALFF) features were identified using group comparisons and logistic regression. Structural equation modeling (SEM) examined relationships among the identified risk dimensions.

Compared with the NSHB group, the SHB group showed greater depressive symptom severity, lower triglyceride, small dense low-density lipoprotein cholesterol (sdLDL-C), and apolipoprotein B levels, higher high-density lipoprotein cholesterol levels, increased right-cuneus mALFF, and decreased mALFF in the left insula, left middle temporal gyrus, left hippocampus, left middle frontal gyrus, and the opercular and triangular parts of the right inferior frontal gyrus. Logistic regression showed that greater depressive symptom severity, reduced sdLDL-C, and altered regional mALFF were associated with increased SHB risk. SEM revealed a pattern of associations linking peripheral lipids, brain function, and SHB, irrespective of depressive symptom severity.

Altered function in regions involved in emotion regulation and impulse control may characterize lipid-related SHB profiles independently of depressive symptom severity. These findings identify candidate biological correlates that may inform future longitudinal studies of SHB-related risk profiles.