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Glutamate normalization with ECT treatment response in major depression

Molecular Psychiatry volume 18, pages 268–270 (2013)Cite this article

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Though psychotherapy, medications and brain stimulation are used to treat major depressive disorder (MDD), treatment response depends on several individualized clinical factors and frequently requires multiple treatment trials. To guide more effective personalized interventions, there is thus a need to identify biological markers to elucidate the mechanisms of response and to predict treatment outcomes in MDD. Prior evidence suggests neurochemical disturbances in mood-regulating networks, including the anterior cingulate cortex (ACC) and connected prefrontal and subcortical centers, contribute to MDD and have a role in treatment response.1, 2, 3, 4 To identify treatment-related changes in neurochemical markers implicated in MDD,2, 4, 5 we applied single-voxel proton magnetic resonance spectroscopy (1HMRS) for cross-sectional and longitudinal analysis of ACC glutamate (Glu), choline (Cho) and N-acetyl aspartate (NAA) in 10 patients with DSM-IVR diagnoses of MDD (mean age: 44.0 years, 7.93 s.d.; 6 females), followed prospectively during index treatment, and 10 demographically similar controls (mean age: 39.03 years, 9.55 s.d.; 6 females). Electroconvulsive therapy (ECT) was used as the therapeutic modality as it is a highly effective procedure for treating severe MDD that elicits rapid response in eligible individuals.6

Metabolites (with variances <20%) did not deviate from normality (Kolmogorov–Smirnov test, all P>0.50). For baseline comparisons, including age and gender as covariates, main effects of diagnosis were observed for Glu only (F(1, 19)=8.61, P<0.01 (lower in patients)). General linear mixed models, including metabolites from each time point and a subject variable to control for within-subject correlations, also showed a significant diagnosis by time interaction for Glu (F(1, 21.98)=4.94, P<0.037). Glu levels increased significantly over time in patients approximating normal levels (F(2, 16.56)=4.05, P<0.037) but remained stable in controls (P=0.47). In patients, subsequent pairwise comparisons showed significant Glu elevations between baseline and the sixth ECT (P<0.018). In the absence of overall effects of time, pairwise comparisons in patients also showed significant decreases in NAA (P<0.048) and increases in Cho (P<0.047) between baseline and the sixth ECT (Figure 1b). HAMD and MADRS scores improved significantly with treatment (F(2, 16.67)=29.48 and F(2, 13.12)=19.79), both P<0.0001. Variations in Glu correlated with MADRS scores across time (F(1, 15.78)=4.49, P<0.05). Baseline Cho levels correlated significantly with overall change in HAMD ratings (r=0.85, P<0.0001); baseline Glu levels also showed a trend for predicting HAMD change (r=0.59, P<0.08; Figure 1c).

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Authors and Affiliations

  1. Ahmanson-Lovelace Brain Mapping Center, Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA

    J Zhang, R P Woods & J R Alger

  2. Laboratory of Neuro Imaging, Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA

    K L Narr & O R Phillips

  3. Department of Neurology and Jane and Terry Semel Institute for Neuroscience and Human Behavior, Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA

    R T Espinoza

  4. Department of Psychiatry, Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA

    R T Espinoza

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  1. J Zhang
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Correspondence to K L Narr.

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Zhang, J., Narr, K., Woods, R. et al. Glutamate normalization with ECT treatment response in major depression. Mol Psychiatry 18, 268–270 (2013). https://doi.org/10.1038/mp.2012.46

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