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


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.

Abstract

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.

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
Language:English
Date:May 2009
Deposited On:25 May 2009 09:02
Last Modified:05 Apr 2016 13:13
Publisher:American Medical Association
ISSN:0003-990X
Publisher DOI:10.1001/archgenpsychiatry.2009.39
PubMed ID:19414707
Permanent URL: http://doi.org/10.5167/uzh-18643

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