Abnormal cingulate and prefrontal cortical neurochemistry in major depression after electroconvulsive therapy.
BACKGROUND
Metabolic changes after electroconvulsive therapy (ECT) have been described in depressed patients, but results are heterogeneous. To determine the concentrations of N-acetyl-aspartate (NAA), choline-containing compounds, creatine + phosphocreatine (tCr), and glutamate in the left dorsolateral prefrontal cortex (DLPFC) and left anterior cingulum of depressed patients before and after ECT, we used proton magnetic resonance spectroscopy.


METHODS
Metabolite concentrations in the DLPFC and anterior cingulum were determined in 25 patients with major depressive disorder (MDD) and 27 healthy control subjects using the point resolved spectroscopy sequence. Neuropsychological and clinical parameters were determined before and after nine sessions of right unilateral ultrabrief pulse ECT.


RESULTS
In the cingulum, baseline glutamate and NAA levels were decreased in depressed patients. High glutamate at baseline predicted a greater treatment response. After ECT, increased NAA levels were observed in responders to treatment and tCr levels were significantly decreased across all depressive patients. In the left DLPFC, NAA levels were significantly decreased in responders to ECT compared with nonresponders. Autobiographic memory was deteriorated in all patients after ECT.


CONCLUSIONS
Low glutamatergic state in depressive patients emphasizes the role of dysfunctional glutamatergic neurotransmission in the pathophysiology of MDD. The low NAA level at baseline in the patients supports neurodegenerative changes in MDD. N-acetyl-aspartate levels might serve as early surrogate marker for dynamic metabolic changes due to ECT, reflecting both neuroprotection and lowered neuronal viability. The tCr decrease in the cingulum suggests altered mitochondrial energy metabolism.
Merkl
Angela
A
Department of Psychiatry Charité-Universitätsmedizin, Campus Benjamin Franklin, Berlin, Germany. angela.merkl@charite.de
Schubert
Florian
F
Quante
Arnim
A
Luborzewski
Alexander
A
Brakemeier
Eva-Lotta
EL
Grimm
Simone
S
Heuser
Isabella
I
Bajbouj
Malek
M
D000328:Adult; D000704:Analysis of Variance; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D003865:Major Depressive Disorder / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy*; D004565:Electroconvulsive Therapy; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006179:Gyrus Cinguli / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011939:Mental Recall; D008875:Middle Aged; D009483:Neuropsychological Tests; D010725:Phosphocreatine / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000503:physiopathology; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014706:Verbal Learning
D010725:Phosphocreatine; D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate; D003401:Creatine