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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-18643

Walter, M; Henning, A; Grimm, S; Schulte, R F; Beck, J; Dydak, U; Schnepf, B; Boeker, H; Boesiger, P; Northoff, G (2009). The relationship between aberrant neuronal activation in the pregenual anterior cingulate, altered glutamatergic metabolism, and anhedonia in major depression. Archives of General Psychiatry, 66(5):478-486.

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Context: Major depressive disorder (MDD) is characterized by diverse metabolic and functional abnormalities that occur in, among other regions, the pregenual anterior cingulate cortex (pgACC), a cortical region linked to anhedonia. Objectives: To contextualize metabolic, functional, and clinical parameters and thus to reveal cellular mechanisms related to anhedonia. Design: The pgACC was investigated using a combined functional magnetic resonance imaging and magnetic resonance spectroscopic approach. Negative blood oxygenation level–dependent (BOLD) activations in the pgACC were assessed during emotional stimulation. Quantitative J-resolved magnetic resonance spectroscopy in the pgACC enabled simultaneous determination of glutamine, glutamate, N-acetylaspartate, glucose, and ɣ-aminobutyric acid concentrations. Subjective emotional intensity ratings as well as various clinical parameters were determined. Setting: The patients were recruited and evaluated in the Department of Psychiatry, University of Zurich, while the measurements were performed in the Institute of Biomedical Engineering, University of Zurich and the Technical University Zurich. Participants: Nineteen unmedicated patients withMDD and 24 healthy subjects. Main Outcome Measures: Reduced glutamine levels and lower functional responses in pgACC in anhedonic depressed patients were expected to be the predominant effect of abnormal glutamatergic transmission. It was further tested if, among patients, the ratings of emotional intensity on visual stimulation predicted the amount of metabolic and functional alterations in terms of reduced relative metabolite concentrations and BOLD changes. Results: Patients with highly anhedonic MDD show decreased glutamine but normal glutamate and ɣ-aminobutyric acid concentrations, with glutamine concentrations being dissociated from glucose concentrations. Glutamate and N-acetylaspartate concentrations in pgACC correlate with negative BOLD responses induced by emotional stimulation in MDD; whereas in healthy subjects, negative BOLD responses correlate with ɣ-aminobutyric acid instead. Negative BOLD responses as well as glutamate and N-acetylaspartate concentrations correlate with emotional intensity ratings, an anhedonia surrogate, in those withMDDbut not in healthy subjects. Conclusion: Aberrant neuronal activation patterns of the pgACC in anhedonic depression are related to deficits of glutamatergic metabolism.


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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Biomedical Engineering
04 Faculty of Medicine > Psychiatric University Hospital Zurich > Clinic for Psychiatry, Psychotherapy, and Psychosomatics
Dewey Decimal Classification:170 Ethics
610 Medicine & health
Date:May 2009
Deposited On:25 May 2009 09:02
Last Modified:27 Nov 2013 18:27
Publisher:American Medical Association
Publisher DOI:10.1001/archgenpsychiatry.2009.39
PubMed ID:19414707

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