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

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.