Right anterior supramarginal gyrus-cerebellum hyperconnectivity and rumination partially mediate the link between childhood abuse and anger in late-life depression

Abstract

Background: Childhood abuse is linked to emotional dysregulation and anger across the lifespan, but its neural correlates in late-life depression (LLD) remain unclear.

Methods: Ninety-eight adults aged ≥60 years with LLD underwent resting-state functional magnetic resonance imaging (rs-fMRI) scan. Childhood abuse (emotional, physical, or sexual) was assessed with the adverse childhood experiences (ACEs) questionnaire, trait anger-hostility with the Revised NEO Personality Inventory (N2), and rumination with the Ruminative Responses Scale. Region of Interest (ROI)-to-ROI resting-state functional connectivity (rs-FC) among 164 atlas regions was compared between participants with and without a history of childhood abuse, controlling for age, gender, education, and depression severity with FDR correction for multiple comparisons. Associations between childhood abuse, rs-FC, and anger were examined using linear regression. Indirect effects were tested with mediation analyses using 5000 bootstrap resamples and bias-corrected confidence intervals.

Results: Participants with childhood abuse histories (n = 52) showed greater rs-FC in three cortico-cerebellar pathways compared with those without childhood abuse histories (n = 46): right anterior supramarginal gyrus (aSMG)-right cerebellar lobule VI, right inferior frontal gyrus (IFG) pars opercularis-left cerebellar lobule X, and left Heschl's gyrus-right cerebellar lobule VI. Childhood abuse was associated with anger-hostility (p = 0.003). Anger-hostility correlated with each of these rs-FCs, but only aSMG-cerebellum rs-FC remained significant on a multivariate basis. In exploratory parallel mediation analyses (n = 83), this rs-FC and rumination showed significant indirect effects, jointly explaining ~50 % of the association of childhood abuse with anger-hostility.

Conclusions: In LLD, aSMG-cerebellar hyperconnectivity and rumination are parallel pathways linking childhood abuse to chronic anger.

Keywords: Adverse childhood experiences; Anger-hostility; Childhood abuse; Late-life depression; Resting-state functional connectivity; Rumination.