Spontaneous neural activity mediates the effect of adverse childhood experiences on negative cognitive styles in mood disorders: a multivariate approach

Abstract

Negative cognitive styles and spontaneous neural activity can reveal cognitive and neurobiological underpinnings of depression, related to poor clinical outcomes and worsened by Adverse Childhood Experiences (ACEs). This study examined the associations between ACEs, fractional Amplitude of Low Frequency Fluctuations (fALFF), and negative cognitive styles in Major Depressive Disorder (MDD) and Bipolar Disorder (BD). In a sample of 94 patients (48 MDD; 46 BD) and 35 matched HC, Canonical Correlation Analysis was used to assess the multivariate association between fALFF and ACEs, rated with the Childhood Trauma Questionnaire. A mediation model tested the role of fALFF in mediating the effect of ACEs on negative cognitive styles, assessed with the Cognitions Questionnaire. In depressed patients, negative cognitive styles were worsened by with ACEs. Cognitive biases were also associated with an ACEs-related spontaneous neural activity pattern, involving the bilateral precuneus and posterior cingulate gyrus, left dorsolateral insula, and right superior temporal gyrus. Moreover, the identified fALFF pattern mediated the effect of ACEs on the perceived uncontrollability of negative events. No significant results were found in HC. These findings highlight fALFF as a promising endophenotype linking ACEs and negative cognitive styles, offering valuable insight into the neurobiological mechanisms underlying mood disorders symptomatology.

Keywords: Canonical correlation analysis; Childhood trauma; Cognitive biases; Mood disorders; Resting-state fMRI.