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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.

SUBMITTER: Song XM

PROVIDER: S-EPMC8760062 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionThere is mounting evidence that visual perception abnormalities in schizophrenia are partly explained by a dysfunction of the lateral occipital complex (LO). We previously demonstrated that schizophrenia patients had broader topography and reduced magnitude of activity of LO. However, the functional connectivity of LO with other brain regions during visual perception has not been directly investigated in schizophrenia.Materials and methodsEighteen patients with schizophrenia and eighteen matched controls performed a backward masking task during functional magnetic resonance imaging (fMRI). Stimulus onset asynchronies were manipulated to change the level of target visibility. To examine connectivity with LO function we conducted psychophysiological interactions (PPI) analyses using: 1) a region of interest (ROI) approach and 2) a whole brain analysis. ROIs were defined based on a contrast of trials on which a target was presented versus null trials in which no stimuli were presented.ResultsEleven ROIs were identified. Both groups showed similar strength of coupling between LO and the 11 ROIs when visibility was not taken into account. Healthy controls showed clear changes in coupling between LO and prefrontal and parietal regions as a function of target visibility (higher coupling with more visible targets). In comparison, patients showed reduced dynamic coupling with LO in the right superior frontal gyrus (significant after correcting for multiple comparisons) and a trend for reduced coupling in the left precuneus and left inferior frontal regions. Whole brain analysis identified additional regions that showed dynamic coupling with LO in healthy controls, but not in patients.DiscussionThe increased coupling between LO and higher-level parietal and prefrontal regions during visual awareness in healthy controls likely reflects visual reentrant processing. The lack of modulation of coupling between LO and key prefrontal and parietal regions found in schizophrenia may partly reflect abnormalities in LO tuning. The altered LO coupling may contribute to visual perception abnormalities in schizophrenia.

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

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