The relationship between aberrant neuronal activation in the pregenual anterior cingulate, altered glutamatergic metabolism, and anhedonia in major depression

Martin Walter, Anke Henning, Simone Grimm, Rolf F. Schulte, Johannes Beck, Ulrike Dydak, Betina Schnepf, Heinz Boeker, Peter Boesiger, Georg Northoff

Research output: Contribution to journalArticlepeer-review

234 Citations (Scopus)


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 oxygen- ation 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, gluta- mate, N-acetylaspartate, glucose, and 7-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 with MDD and 24 healthy subjects. Main Outcome Measures: Reduced glutamine level and lower functional responses in pgACC in anhedoni depressed patients were expected to be the predominan effect of abnormal glutamatergic transmission. It wa further tested if, among patients, the ratings of emotiona intensity on visual stimulation predicted the amount o metabolic and functional alterations in terms of reduce relative metabolite concentrations and BOLD changes. Results: Patients with highly anhedonic MDD show decreased glutamine but normal glutamate an 7-aminobutyric acid concentrations, with glutamine con centrations being dissociated from glucose concentra tions. Glutamate and N-acetylaspartate concentrations ii pgACC correlate with negative BOLD responses in duced by emotional stimulation in MDD; whereas ii healthy subjects, negative BOLD responses correlate with 7-aminobutyric acid instead. Negative BOLD response: as well as glutamate and N-acetylaspartate concentra tions correlate with emotional intensity ratings, an an hedonia surrogate, in those with MDD but not in health subjects. Conclusion: Aberrant neuronal activation patterns of th pgACC in anhedonic depression are related to deficit of glutamatergic metabolism.

Original languageEnglish
Pages (from-to)478-486
Number of pages9
JournalArchives of General Psychiatry
Issue number5
Publication statusPublished - May 2009

ASJC Scopus subject areas

  • Psychiatry and Mental health


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