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


OBJECTIVE
To contextualize metabolic, functional, and clinical parameters and thus to reveal cellular mechanisms related to anhedonia.


METHODS
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 gamma-aminobutyric acid concentrations. Subjective emotional intensity ratings as well as various clinical parameters were determined.


METHODS
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.


METHODS
Nineteen unmedicated patients with MDD and 24 healthy subjects.


METHODS
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 gamma-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 gamma-aminobutyric acid instead. Negative BOLD responses as well as glutamate and N-acetylaspartate concentrations correlate with emotional intensity ratings, an anhedonia surrogate, in those with MDD but not in healthy subjects.


CONCLUSIONS
Aberrant neuronal activation patterns of the pgACC in anhedonic depression are related to deficits of glutamatergic metabolism.
Department of Psychiatry, Ottovon-Guericke University of Magdeburg, Magdeburg, Germany.
Martin
M
Walter
Anke
A
Henning
Simone
S
Grimm
Rolf F
RF
Schulte
Johannes
J
Beck
Ulrike
U
Dydak
Betina
B
Schnepf
Heinz
H
Boeker
Peter
P
Boesiger
Georg
G
Northoff
D000328:Adult; D001143:Arousal / Q000502:physiology; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D003337:Corpus Callosum / Q000503:physiopathology*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000503:physiopathology* / Q000523:psychology; D004292:Dominance, Cerebral / Q000502:physiology; D004644:Emotions / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism; D006179:Gyrus Cinguli / Q000503:physiopathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000502:physiology; D010101:Oxygen Consumption / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D001786:Blood Glucose; D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C000179:N-acetylaspartate