Elsevier

Biological Psychiatry

Volume 69, Issue 8, 15 April 2011, Pages 772-779
Biological Psychiatry

Archival Report
Abnormal Cingulate and Prefrontal Cortical Neurochemistry in Major Depression After Electroconvulsive Therapy

https://doi.org/10.1016/j.biopsych.2010.08.009Get rights and content

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.

Section snippets

Participants

A total of 27 patients fulfilling the diagnostic criteria for MDD (DSM-IV) and referred to ECT due to clinical indication and 27 healthy sex-matched control subjects were enrolled from January 2005 to December 2008. Diagnoses were established by two independent experienced psychiatrists based on a clinical interview following DSM-IV criteria. Patients with a medical history of alcohol und drug abuse, schizophrenia, or dementia were excluded. Medication resistance was measured with the

Results

Gender, age, length of index episode, lifetime number of depressive episodes, Beck Depression Inventory, and Montgomery Åsberg Rating Scale sores at T0, at T_acute, and at T1 are summarized in Table 1. Clinical outcome was calculated at T_acute and showed an initial early response rate of 32% (response criteria of 50% HDRS score reduction); after continuation, 68% of the patients responded to RUL ECT (Table 1). Nonresponse and withdrawal of ECT were defined by a senior psychiatrist considering

Discussion

The main findings of the present study are 1) reduced glutamate and NAA levels in the anterior cingulum in patients with depression compared with healthy subjects, 2) that a high glutamate at T0 predicted a greater improvement after ECT, and 3) decreased NAA levels in the DLPFC and increased NAA levels in the anterior cingulum in responders to ECT. Additionally, in the anterior cingulum, tCr levels were significantly decreased after ECT across all patients.

The observed diminished anterior

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