Overlapping and segregated resting‐state functional connectivity in patients with major depressive disorder with and without childhood neglect

TLDR

Childhood maltreatment increases the risk of major depressive disorder and predicts poorer treatment outcomes, yet the neural mechanisms underlying this association remain poorly understood. This study aimed to examine whole‑brain functional connectivity patterns in MDD patients with a history of childhood neglect. Resting‑state fMRI data from 18 MDD patients with neglect, 20 without neglect, and 20 healthy controls were used to construct voxel‑wise functional networks, which were then analyzed with graph‑theory metrics. Both MDD groups showed reduced connectivity in bilateral ventral medial prefrontal cortex/ventral anterior cingulate cortex, while the neglect group exhibited additional widespread reductions in prefrontal‑limbic‑thalamic‑cerebellar circuitry that correlated with neglect severity, demonstrating overlapping and segregated network alterations. Hum Brain Mapp 35:1154–1166, 2014, © 2013 Wiley Periodicals, Inc.

Abstract

Many studies have suggested that childhood maltreatment increase risk of adulthood major depressive disorder (MDD) and predict its unfavorable treatment outcome, yet the neural underpinnings associated with childhood maltreatment in MDD remain poorly understood. Here, we seek to investigate the whole‐brain functional connectivity patterns in MDD patients with childhood maltreatment. Resting‐state functional magnetic resonance imaging was used to explore intrinsic or spontaneous functional connectivity networks of 18 MDD patients with childhood neglect, 20 MDD patients without childhood neglect, and 20 healthy controls. Whole‐brain functional networks were constructed by measuring the temporal correlations of every pairs of brain voxels and were further analyzed by using graph‐theory approaches. Relative to the healthy control group, the two MDD patient groups showed overlapping reduced functional connectivity strength in bilateral ventral medial prefrontal cortex/ventral anterior cingulate cortex. However, compared with MDD patients without a history of childhood maltreatment, those patients with such a history displayed widespread reduction of functional connectivity strength primarily in brain regions within the prefrontal‐limbic‐thalamic‐cerebellar circuitry, and these reductions significantly correlated with measures of childhood neglect. Together, we showed that the MDD groups with and without childhood neglect exhibited overlapping and segregated functional connectivity patterns in the whole‐brain networks, providing empirical evidence for the contribution of early life stress to the pathophysiology of MDD. Hum Brain Mapp 35:1154–1166, 2014 . © 2013 Wiley Periodicals, Inc.