The Gamma-aminobutyric acid (GABA) and glutamate (Glu) neurotransmitter systems are implicated in depression. While previous studies found reduced GABA levels, and a tendency towards reduced Glu, using proton (1H) magnetic resonance spectroscopy (1H-MRS), little is known about GABAA receptor availability in depression. Here, the aim was to characterize GABA and Glu-levels in dorsal anterior cingulate cortex (dACC), whole-brain GABAA availability, and their relationship in patients with depression compared to healthy controls. Forty-two patients and 45 controls underwent 1H-MRS using a MEGA-PRESS sequence to quantify dACC GABA+ and Glu (contrasted against creatine [Cr]). Immediately preceding the 1H-MRS, a subsample of 28 patients and 15 controls underwent positron emission tomography (PET) with [11C]Flumazenil to assess whole-brain GABAA receptor availability. There were no differences in dACC GABA+/Cr or Glu/Cr ratios between patients and controls. The same was true for whole-brain GABAA receptor availability. However, there was a significant negative relationship between GABA+/Cr ratio and receptor availability in ACC, in a whole-brain voxel-wise analysis across patients and controls, controlling for group or depressive symptoms. This relatively large study did not support the GABA-deficit hypothesis in depression, but shed light on GABA-system functioning, suggesting a balance between neurotransmitter concentration and receptor availability in dACC.
Keywords: Depression; GABA; Glutamate; Magnetic resonance spectroscopy; PET.
Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.