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.

Altered Visual Cortical Excitability Is Associated With Psychopathological Symptoms in Major Depressive Disorder

“…Indeed, many lines of studies have reported that MDD is often associated with the subjective experience of altered visual perception, such as photophobia, perceived dimness and reduced visual contrast discrimination ( 49 – 51 ). Moreover, the impairment in visual perception was found to be directly related to the psychopathological symptoms of MDD ( 4 , 8 ). In our study, we found PPS, as indicated by amplitude ratios (A2s/A1), was significantly related to the symptom severity of depression.…”

“…The psychophysical deficits in visual perception in MDD are closely related to the abnormality of biochemical changes in the occipital cortex. Using proton magnetic resonance spectroscopy, previous studies have consistently shown a decreased concentration of gamma-aminobutyric acid (GABA) in the visual cortex of MDD subjects (6)(7)(8), which can be normalized following effective therapeutic interventions (9)(10)(11). As an important inhibitory neurotransmitter, GABA was considered to mediate the centersurround suppression effect in visual perception (12).…”

“…In healthy individuals, excitatory glutamate levels were found to have a positive association with GABA levels, indicating an excitation-inhibition balance in the occipital cortex. However, in MDD, there was a reduction in glutamate levels in the occipital cortex, and, more importantly, the balance between GABA and glutamate levels was disrupted ( 8 ).…”

Reduced inhibition in depression impairs stimulus processing in human cortical microcircuits

“…Other studies that used the Paced Visual Serial Addition Test and Inspection Time Test found that depression patients had slower visual processing speeds and made more calculation errors compared to healthy controls 37,38 . Depression patients have also been shown to perform worse on visual processing tasks such as the Stroop Colour Word Test and in visual surround motion suppression 39,40 . Our demonstration of similar effects on cortical processing of apical (cortico-cortical inputs) and the canonical nature of the cortical microcircuitry 41 also generalize the implications of our results to higher-order deficits 42 , an important topic that can be explored carefully in future studies.…”

Selective activation of ABCA1/ApoA1 signaling in the V1 by magnetoelectric stimulation ameliorates depression via regulation of synaptic plasticity

“…Previous studies have revealed that structural and functional abnormalities of the visual cortex may be related to the pathogenesis of depression. For example, gamma-aminobutyric acid (GABA) levels ( Kugaya et al., 2003 ; Price et al., 2009 ) and GABAergic neurons ( Maciag et al., 2010 ) are remarkably decreased in the occipital cortex of MDD patients, which may relate to abnormalities in visual perception and psychopathological symptoms ( Song et al., 2021 ). Compared with healthy controls, MDD patients exhibit reduced voxel-mirrored homotopic connectivity of the visual cortex, which is negatively associated with Hamilton Depression Rating Scale scores ( Deng et al., 2021 ).…”