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Anterior Cingulate Cortexγ-Aminobutyric Acid in Depressed Adolescents: Relationship to Anhedonia
Open accessAbstract
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.
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“An imbalance between two primary central nervous system (CNS) neurotransmitters, L-glutamate and γ-aminobutyric acid (GABA), has emerged as having a key role in the pathophysiology of TRD.”
From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [19]
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“Glutamatergic and GABAergic dysfunction in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC) has been extensively implicated in both MDD and TRD [16,17,18,19,20,21,22,23,24,25].”
From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [19]
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“In both MDD and TRD, region-specific normalization of GABA concentrations in the occipital cortex (OCC), ACC, and DMN have repeatedly been observed in response to all successful antidepressant therapies [19,22,23,63].”
From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [19]
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“Several human MRS studies have reported lower mPFC GABA levels in MDD (139–141).”
From The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology (2019) · cites this paper as [140]
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“In the CNS, reductions in ACC GABA levels appear to correlate with increased anhedonia and treatment resistance [19,23].”
From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [19]
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Metadata
- Authors
- Gabbay, V.
- Affiliations
- NYU Langone Health (US)
- Corresponding author
- Gabbay, Vilma
- ORCID
- Gabbay, Vilma
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2012-02-01
- Volume
- 69
- Issue
- 2
- Pages
- 139
- ISSN
- 0003-990X (ISSN-L)
- PMC
- PMC3711232
- OpenAlex
- W2099029781
- Cited by
- 201
- References
- 67
- Citations by year
- 2026: 12 · 2025: 6 · 2024: 15 · 2023: 13 · 2022: 12 · 2021: 18 · 2020: 15 · 2019: 15 · 2018: 13 · 2017: 16 · 2016: 16 · 2015: 13 · 2014: 15 · 2013: 14 · 2012: 8
- FWCI
- 8.67
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (MH075895, MH077072, MH077072-03S1, K23MH077072, R01MH075895)
- National Center for Complementary and Integrative Health (R21AT002395, R21AT004576, AT004576, AT002395)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- anterior cingulate cortex, GABA, adolescent depression, anhedonia, major depressive disorder, white matter, 1H NMR
- MeSH terms
- Adolescent, Child, Cross-Sectional Studies, Major Depressive Disorder, Depressive Disorder, Major, Female, gamma-Aminobutyric Acid, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Male, Magnetic Resonance Spectroscopy, Case-Control Studies, Neurotransmitter Agents, Young Adult, Anhedonia, Neuroimaging
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