PMC

Scatterplots of raw data of anterior cingulate cortex γ-aminobutyric acid relative to unsuppressed voxel tissue water concentrations (GABA/w) in healthy controls and adolescents with major depressive disorder (MDD) (A) and healthy controls, nonanhedonic adolescents with MDD, and anhedonic adolescents with MDD (B). Open circles represent subjects with melancholic MDD.

Scatterplots with regression lines characterizing associations of γ-aminobutyric acid level relative to unsuppressed voxel tissue water (GABA/w) values and major depressive disorder (MDD) severity scores in all 20 subjects with MDD (A); anhedonia scores in the 10 subjects with MDD categorized as anhedonic (B); anhedonia scores in all 20 subjects with MDD (C); and anhedonia scores in the combined group of subjects with MDD and healthy controls (D).

Illustration of the γ-aminobutyric acid (GABA)–glutamine and glutamate-glutamine cycles. Astrocytes release glutamine, which is absorbed by GABAergic and glutamatergic neurons, where it is metabolized into GABA and glutamate, respectively. These neurotransmitters regulate dopaminergic neurons; preclinical and clinical evidence suggest that alterations in GABA and glutamate signaling may induce major depressive disorder and anhedonia symptoms via this mechanism. Following release, GABA and glutamate molecules are absorbed by astrocytes and converted back into glutamine. H₂N indicates primary amine group; HO, hydroxyl group; NH₂, primary amine group; O, oxygen; OH, hydroxyl group.

Axial (A) and sagittal (B) images showing anterior cingulate cortex voxel size and location and volume-selective point-resolved spectroscopy proton magnetic resonance spectra (C) with the editing radiofrequency pulse on (a) and off (b). With the editing pulse off (b), a standard point-resolved spectroscopy spectrum is obtained, which yields high-quality spectra for N-acetylaspartate (NAA), total creatine (tCr), and total choline (tCho) in the anterior cingulate cortex. The difference of the spectra in parts a and b showing the edited γ-aminobutyric acid (GABA) and combined resonances of glutamate and glutamine (Glx) peaks (c), with the best-fit model curve of the edited spectrum (d), the individual components of the best-fit curve (e), and the residuals of the difference between the edited (c) and best-fit (d) spectra (f ). The data were acquired in 15 minutes from a 2.5 ×2.5 ×3.0-cm³ voxel using a repetition time of 1500 milliseconds, echo time of 68 milliseconds, and 290 interleaved excitations (total, 580) with the editing pulse on or off.