Neurochemical correlates of rapid treatment response to electroconvulsive therapy in patients with major depression

Neurochemical correlates of rapid treatment response to electroconvulsive therapy in patients with major depression

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J Psychiatry Neurosci 2017;42(1):6-16

Stephanie Njau, BA; Shantanu H. Joshi, PhD; Randall Espinoza, MD; Amber M. Leaver, PhD; Megha Vasavada, PhD; Antonio Marquina, PhD; Roger P. Woods, MD; Katherine L. Narr, PhD

Abstract

Background: Electroconvulsive therapy (ECT) is a highly effective brain stimulation treatment for severe depression. Identifying neurochemical changes linked with ECT may point to biomarkers and predictors of successful treatment response.

Methods: We used proton magnetic resonance spectroscopy (1H-MRS) to measure longitudinal changes in glutamate/glutamine (Glx), creatine (Cre), choline (Cho) and N-acetylaspartate (NAA) in the dorsal (dACC) and subgenual anterior cingulate cortex (sgACC) and bilateral hippocampus in patients receiving ECT scanned at baseline, after the second ECT session and after the ECT treatment series. Patients were compared with demographically similar controls at baseline. Controls were assessed twice to establish normative values and variance.

Results: We included 50 patients (mean age 43.78 ± 14 yr) and 33 controls (mean age 39.33 ± 12 yr) in our study. Patients underwent a mean of 9 ± 4.1 sessions of ECT. At baseline, patients showed reduced Glx in the sgACC, reduced NAA in the left hippocampus and increased Glx in the left hippocampus relative to controls. ECT was associated with significant increases in Cre in the dACC and sgACC and decreases in NAA in the dACC and right hippocampus. Lower NAA levels in the dACC at baseline predicted reductions in depressive symptoms. Both ECT and symptom improvement were associated with decreased Glx in the left hippocampus and increased Glx in the sgACC.

Limitations: Attrition and clinical heterogeneity may have masked more subtle findings.

Conclusion: ECT elicits robust effects on brain chemistry, impacting Cre, NAA and Glx, which suggests restorative and neurotrophic processes. Differential effects of Glx in the sgACC and hippocampus, which approach control values with treatment, may reflect previously implicated underactive cortical and overactive subcortical limbic circuitry in patients with major depression. NAA levels at baseline are predictive of therapeutic outcome and could inform future treatment strategies.


Submitted May. 18, 2015; Revised July 30, 2015; Accepted Jan. 31, 2016; Early-released June 23, 2016

Affiliations: From the Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California, Los Angeles, Calif., USA (Njau, Joshi, Leaver, Vasavada, Woods, Narr); the Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Calif., USA (Espinoza, Woods, Narr); and the Department of Mathematics, University of Valencia, Valencia, Spain (Marquina).

Funding: This study was supported by grant numbers R01MH092301 and K24MH102743 from the National Institute of Mental Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health.

Competing interests: None declared.

Contributors: R. Espinoza and K. Narr designed the study. S. Njau, A. Leaver, M. Vasavada and K. Narr acquired the data, which S. Njau, S. Joshi, R. Espinoza, A. Marquina, R. Woods and K. Narr analyzed. S. Njau wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.150177

Correspondence to: K. Narr, 635 Charles E Young Dr S #225, University of California Los Angeles, Los Angeles CA 90095; narr@ucla.edu