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EV0849

Neurotransmitters in the pregenual anterior cingulate cortex modulate intrinsic functional connectivity within the default mode network in first-episode, treatment-naïve patients with major depressive disorder

NEUROTRANSMITTERS IN THE PREGENUAL ANTERIOR CINGULATE CORTEX REGULATE INTRINSIC FUNCTIONAL CONNECTIVITY IN THE DEFAULT MODE NETWORK IN FIRST-EPISODE UNTREATED MAJOR DEPRESSIVE DISORDER PATIENTS

A reduced GABA+/Glx ratio in the pregenual anterior cingulate cortex is associated with anhedonia through functional connectivity within the default mode network in first-episode, treatment-naïve patients with major depressive disorder.

The study aimed to investigate the mechanisms through which the GABA+/Glx ratio mediates anhedonia in major depressive disorder (MDD) using multimodal imaging. Twenty-six first-episode, treatment-naïve patients with MDD and 25 healthy controls (HCs) were assessed using the Snaith–Hamilton Pleasure Scale (SHAPS); GABA+, the glutamate–glutamine complex (Glx), and the GABA+/Glx ratio in the pregenual anterior cingulate cortex (pgACC) were measured using edited proton magnetic resonance spectroscopy (1H MRS), while indices of local pgACC activity and its functional connectivity (FC) with other key nodes of the default mode network (DMN) were assessed using functional magnetic resonance imaging (fMRI). For the primary outcomes, GABA+ levels were 1.41 ± 0.54 in the MDD group and 1.58 ± 0.56 in the HC group (β=-0.12, p=0.27); Glx levels were 7.49 ± 1.31 and 6.84 ± 1.07 (β=0.10, p=0.04); and GABA+/Glx ratios were 0.19 ± 0.06 and 0.23 ± 0.08 (β=-0.22, p=0.03), respectively. For the secondary outcomes, no significant between-group differences were found for NAA (7.94 ± 0.59 and 7.75 ± 0.72, p=0.31), Cho (1.29 ± 0.28 and 1.26 ± 0.13, p=0.67), or Cr (6.80 ± 0.60 and 6.66 ± 0.64, p=0.53). Functional connectivity between the left pgACC and the left subgenual anterior cingulate cortex differed between groups, and this connectivity was negatively correlated with the GABA+/Glx ratio in the MDD group (r=-0.49, p=0.016); no significant correlation was observed in healthy controls (r=-0.18, p=0.426). The GABA+/Glx ratio in the pgACC was negatively associated with SHAPS scores through this functional connectivity. In conclusion, a reduced GABA+/Glx ratio in the pgACC may be a distinguishing biomarker for first-episode, treatment-naïve patients with MDD, and this ratio may influence anhedonic symptoms by modulating functional connectivity within the DMN.

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