Longitudinal changes in amygdala-supplementary motor area connectivity and their association with recurrent self-harm in adolescents with mood disorders.

BACKGROUND

Adolescents hospitalized with mood disorders face a heightened risk of repeated self-harm (SH) after discharge. Neuroimaging phenotype may complement traditional symptom-based approaches by revealing neural mechanisms of SH vulnerability. This study aimed to investigate longitudinal changes in functional connectivity (FC) in adolescents with repeated SH and to examine how these neural dynamics relate to SH-related symptoms.

METHODS

We recruited 201 adolescent inpatients with mood disorders and SH behaviors, who were classified into repeated (RESH; n = 63) and non-repeated (NRESH; n = 138) SH groups based on a six-month follow-up. Resting-state fMRI and clinical assessments were conducted at three time points: acute (T1, admission ≤ 1 week), subacute (T2, 1-2 weeks), and discharge (T3). Voxel-wise ANCOVA identified regions showing significant group-by-time interaction effects in amygdala functional connectivity. Partial least squares correlation (PLSC) was used to examine associations between changes in FC (ΔFC) and suicidal symptoms, while logistic regression tested whether baseline and dynamic FC predicted SH recurrence at follow-up.

RESULTS

ANCOVA revealed significant group-by-time interaction effects in amygdala-cortical connectivity, particularly with the left supplementary motor area (L-SMA) (Gaussian random field, GRF corrected, P < 0.05). PLSC showed that ΔFC between the amygdala and L-SMA was significantly associated with suicidal measures. Logistic regression indicated that both baseline (AUC = 0.75, 95% CI: 0.63-0.79) and ΔFC (AUC = 0.76, 95% CI: 0.68-0.82) between the amygdala and L-SMA, along with sex and Beck Scale for Suicide Ideation (BSS) item 3("Reasons for Living or Dying"), were significant predictors of SH behavior.

CONCLUSIONS

Longitudinal changes in amygdala-L-SMA connectivity are associated with suicidal symptoms and predict SH recurrence, supporting the integration of neurobiological and clinical indicators for early suicide risk stratification.

CLINICAL TRIAL NUMBER: Not applicable.