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Anterior cingulate cortex ?-aminobutyric acid in depressed adolescents: relationship to anhedonia.

ABSTRACT: 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 ?-aminobutyric acid (GABA).To test whether anterior cingulate cortex (ACC) GABA levels, measured by proton magnetic resonance spectroscopy, are decreased in adolescents with MDD. The associations of GABA alterations with the presence and severity of anhedonia were explored.Case-control, cross-sectional study using single-voxel proton magnetic resonance spectroscopy at 3 T.Two clinical research divisions at 2 teaching hospitals.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.Anterior cingulate cortex GABA levels expressed as ratios relative to unsuppressed voxel tissue water (w) and anhedonia scores expressed as a continuous variable.Compared with control subjects, adolescents with MDD had significantly decreased ACC GABA/w (t = 3.2; P < .003). When subjects with MDD 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 MDD compared with controls (P = .04).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.

SUBMITTER: Gabbay V

PROVIDER: S-EPMC3711232 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Anterior cingulate cortex γ-aminobutyric acid in depressed adolescents: relationship to anhedonia.

Gabbay Vilma V Mao Xiangling X Klein Rachel G RG Ely Benjamin A BA Babb James S JS Panzer Aviva M AM Alonso Carmen M CM Shungu Dikoma C DC

Archives of general psychiatry 20111003 2

<h4>Context</h4>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 γ-aminobutyric acid (GABA).<h4>Objective</h4>To test whether anterior cingulate cortex (ACC) GABA levels, measured by proton magnetic resonance spectroscopy, are decreased in adolescents with MDD. The associations of GABA alterations with the presence and severity of anhedonia were explor ...[more]

PMID: 21969419

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Project description:BackgroundDepression has been associated with low-grade elevation of plasma cytokines (e.g. interleukin-6, IL-6; tumor necrosis factor alpha, TNFα) in both cross-sectional and longitudinal studies in adults. Preclinical and clinical studies also suggest that IL-6 and TNFα elevation are associated with anhedonia. However, few studies have examined longitudinal relationships between cytokines and depression/anhedonia in clinically depressed samples, particularly adolescents.MethodsThirty-six adolescents with a depressive disorder receiving standard-of-care community treatment were assessed at a baseline and a follow-up timepoint. Self-report and clinical measures of depression and anhedonia, along with plasma IL-6 and TNFα levels, were obtained at both timepoints. Baseline cytokine measures were examined in association with baseline and follow-up clinical measures. On an exploratory basis, change in clinical measures over time was examined in relation to change in cytokine levels over time.ResultsHigher baseline TNFα levels predicted higher follow-up depression severity after approximately four months (controlling for baseline depression). Higher baseline TNFα levels also associated positively with baseline anhedonia and predicted higher anhedonia at follow-up (controlling for baseline anhedonia). No association was found between change in clinical measures and change in cytokine levels over time.ConclusionsAmong adolescents receiving standard-of-care community treatment for depression, higher levels of TNFα predicted greater depressive symptoms at 4-month follow-up, suggesting this cytokine may be used to help identify patients in need of more intensive treatment. Elevated TNFα levels were also associated with concurrent and future anhedonia symptoms, suggesting a specific mechanism in which TNFα affects depression trajectories. Future studies should examine the relationships between cytokine levels and depression/anhedonia symptoms at multiple timepoints in larger cohorts of depressed adolescents.

Dataset Information

Anterior cingulate cortex ?-aminobutyric acid in depressed adolescents: relationship to anhedonia.

Publications

Anterior cingulate cortex γ-aminobutyric acid in depressed adolescents: relationship to anhedonia.

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