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

TitleAnterior cingulate cortex γ-aminobutyric acid in depressed adolescents: relationship to anhedonia.
Publication TypeJournal Article
Year of Publication2012
AuthorsGabbay V, Mao X, Klein RG, Ely BA, Babb JS, Panzer AM, Alonso CM, Shungu DC
JournalArch Gen Psychiatry
Volume69
Issue2
Pagination139-49
Date Published2012 Feb
ISSN1538-3636
KeywordsAdolescent, Anhedonia, Case-Control Studies, Child, Cross-Sectional Studies, Depressive Disorder, Major, Female, gamma-Aminobutyric Acid, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Male, Neuroimaging, Neurotransmitter Agents, Young Adult
Abstract

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 γ-aminobutyric acid (GABA).

OBJECTIVE: 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.

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 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).

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.

DOI10.1001/archgenpsychiatry.2011.131
Alternate JournalArch Gen Psychiatry
PubMed ID21969419
PubMed Central IDPMC3711232
Grant ListR01 MH075895 / MH / NIMH NIH HHS / United States
AT004576 / AT / NCCIH NIH HHS / United States
AT002395 / AT / NCCIH NIH HHS / United States
MH075895 / MH / NIMH NIH HHS / United States
MH077072-03S1 / MH / NIMH NIH HHS / United States
MH077072 / MH / NIMH NIH HHS / United States
R21 AT004576 / AT / NCCIH NIH HHS / United States
K23 MH077072 / MH / NIMH NIH HHS / United States
R21 AT002395 / AT / NCCIH NIH HHS / United States
Related Institute: 
MRI Research Institute (MRIRI)

Weill Cornell Medicine
Department of Radiology
525 East 68th Street New York, NY 10065