Anterior Cingulate Cortex γ-Aminobutyric Acid in Depressed Adolescents

Context: Anhedonia, a core symptom of major depressive disorder (MDD) and highly variable among adolescents with MDD, may involve alterations in the major inhibitory amino acid neurotransmitter system of gamma-aminobutyric acid (GABA). Objective: To test whether anterior cingulate cortex (ACC) GABA levels, measured by proton magnetic resonance spectroscopy, are decreased in adolescents with M DD. The associations of GABA alterations with the presence and severity of anhedonia were explored. Design: Case-control, cross-sectional study using single-voxel proton magnetic resonance spectroscopy at 3 T. Setting: Two clinical research divisions at 2 teaching hospitals. Participants: Twenty psychotropic medication-free adolescents with MDD (10 anhedonic, 12 female, aged 12-19 years) with episode duration of 8 weeks or more and 21 control subjects group matched for sex and age. Main Outcome Measures: Anterior cingulate cortex GABA levels expressed as ratios relative to unsuppressed voxel tissue water (w) and anhedonia scores expressed as a continuous variable. Results: Compared with control subjects, adolescents with MDD had significantly decreased ACC GABA/w (t = 3.2; P<.003). When subjects with M DD were categorized based on the presence of anhedonia, only anhedonic patients had decreased GABA/w levels compared with control subjects (t=4.08; P<.001; P-Tukey <.001). Anterior cingulate cortex GABA/w levels were negatively correlated with anhedonia scores for the whole MDD group (r=-0.50; P=.02), as well as for the entire participant sample including the control subjects (r=-0.54; P <.001). Anterior cingulate cortex white matter was also significantly decreased in adolescents with M DD compared with controls (P=.04). Conclusions: These findings suggest that GABA, the major inhibitory neurotransmitter in the brain, may be implicated in adolescent MDD and, more specifically, in those with anhedonia. In addition, use of a continuous rather than categorical scale of anhedonia, as in the present study, may permit greater specificity in evaluating this important clinical feature.