Reduction of higher-order occipital GABA and impaired visual perception in acute major depressive disorder

Xue Mei Song,Zhe Li,Xi-Wen Hu,Qian-Nan Wang,Xuan Ju,Zhong-Lin Tan,Dong-Yu Liu,Georg Northoff,Ruiliang Bai,Yuan Gao,Chuang Xue,Yong-Chun Cai

doi:10.1038/s41380-021-01090-5

Abstract

Major depressive disorder (MDD) is a complex state-dependent psychiatric illness for which biomarkers linking psychophysical, biochemical, and psychopathological changes remain yet elusive, though. Earlier studies demonstrate reduced GABA in lower-order occipital cortex in acute MDD leaving open its validity and significance for higher-order visual perception, though. The goal of our study is to fill that gap by combining psychophysical investigation of visual perception with measurement of GABA concentration in middle temporal visual area (hMT+) in acute depressed MDD. Psychophysically, we observe a highly specific deficit in visual surround motion suppression in a large sample of acute MDD subjects which, importantly, correlates with symptom severity. Both visual deficit and its relation to symptom severity are replicated in the smaller MDD sample that received MRS. Using high-field 7T proton Magnetic resonance spectroscopy (1H-MRS), acute MDD subjects exhibit decreased GABA concentration in visual MT+ which, unlike in healthy subjects, no longer correlates with their visual motion performance, i.e., impaired SI. In sum, our combined psychophysical-biochemical study demonstrates an important role of reduced occipital GABA for altered visual perception and psychopathological symptoms in acute MDD. Bridging the gap from the biochemical level of occipital GABA over visual-perceptual changes to psychopathological symptoms, our findings point to the importance of the occipital cortex in acute depressed MDD including its role as candidate biomarker.

Highlights

Major depressive disorder (MDD) is a complex, usually recurring psychiatric illness characterized by pervasive disturbances, such as mood dysregulation, impaired cognitive control and behavior [1]
We demonstrate occipital GABA deficit in acute MDD and impaired visual perception with the latter relating to symptom severity
We found significantly lower GABA concentration in hMT+ of acute depressed MDD subjects compared to healthy control subjects (Fig. 3 a)

Summary

Introduction

Major depressive disorder (MDD) is a complex, usually recurring psychiatric illness characterized by pervasive disturbances, such as mood dysregulation, impaired cognitive control and behavior [1]. Occipital GABA levels in MDD are state-dependent [11] as they show “normalization” after successful electroconvulsive [12], cognitive behavioral therapy [13] and psychopharmacological treatment with selective serotonin reuptake inhibitors (SSRI [14]) Together, these studies suggest occipital GABA to be a promising candidate biomarker of the acute depressed state. These findings leave open whether occipital GABA is directly related to psychophysical impairment in visual perception and to psychopathological symptoms of MDD—this would further strengthen confidence in both its validity [8] and utility as biomarker of the acute depressed state Filling this gap in our knowledge by combining psychophysical investigation of visual perception with biochemical measurement of occipital GABA in acute depressed MDD is the main aim of our study

Objectives

Methods

Results

Discussion

Conclusion