Common and distinct global functional connectivity density alterations in drug-naïve patients with first-episode major depressive disorder with and without auditory verbal hallucination

Abstract

Auditory verbal hallucination (AVH), defined as the auditory perception of speech in the absence of a real external stimulus, occurs in individuals with and without mental illness. The distribution of functional abnormalities in patients with AVH suggests aberrant brain network connectivity. However, no study has measured the global functional connectivity density (gFCD) associated with AVH in patients with major depressive disorder (MDD); gFCD is used widely to examine the density distribution of whole-brain resting-state functional connectivity and can serve as an index reflecting brain metabolism disturbance. In this study, we involved drug-naïve patients with first-episode MDD with (n = 35) and without (n = 40) AVH and healthy controls (n = 50).Whole-brain resting-state functional magnetic resonance imaging data were acquired and gFCD was calculated and compared among groups. We found the following gFCD alterations that were shared by both MDD groups: (1) decreased gFCD in the bilateral postcentral gyrus, precentral gyrus, insular cortices and occipital lobe; and (2) increased gFCD in the left middle cingulate cortex. More importantly, we found AVH-specific gFCD changes in patients with MDD: increased gFCD in the left Wernicke's brain regions and bilateral hippocampus and thalamus, and decreased gFCD in the bilateral lateral prefrontal lobule. These findings reflect the disturbance of brain information communication and metabolism in patients with MDD and AVH, related mainly to the language and memory processing circuits, and to some extent provide further support for the "VOICE" model of AVH.

Keywords: Auditory verbal hallucination; Global functional connectivity density; Hippocampus; Major depressive disorder; Thalamus; Wernicke's brain region.