Electroconvulsive therapy-induced brain plasticity determines therapeutic outcome in mood disorders

Abstract

There remains much scientific, clinical, and ethical controversy concerning the use of electroconvulsive therapy (ECT) for psychiatric disorders stemming from a lack of information and knowledge about how such treatment might work, given its nonspecific and spatially unfocused nature. The mode of action of ECT has even been ascribed to a "barbaric" form of placebo effect. Here we show differential, highly specific, spatially distributed effects of ECT on regional brain structure in two populations: patients with unipolar or bipolar disorder. Unipolar and bipolar disorders respond differentially to ECT and the associated local brain-volume changes, which occur in areas previously associated with these diseases, correlate with symptom severity and the therapeutic effect. Our unique evidence shows that electrophysical therapeutic effects, although applied generally, take on regional significance through interactions with brain pathophysiology.

Keywords: hippocampus; magnetic resonance imaging; unipolar depression; voxel-based morphometry.

Fig. 1.

Schematic representation of study design and statistical analyses. ECT given at any time point if clinically indicated.

Fig. 2.

Imaging and behavioral results. (A) Plot of mean HDRS scores for all time points. (B) Results of voxel-based morphometry analyses showing ECT-induced increases and decreases in GMV. For representation purposes, results are displayed at significance threshold of P < 0.001 uncorrected at voxel level and a cluster extent threshold of 200 voxels. Coordinates corresponding to Montreal Neurological Institute standard space. CI, confidence interval; an asterisk represents significant at a cluster extent threshold of P < 0.05 family-wise error corrected for multiple comparisons and adjusted for nonstationarity of smoothness (28). (C) Mean GMV at baseline and after treatment displayed for ECT, no-ECT patients, and control subjects (first two time points). **Significant difference between the groups in an ANOVA; *significant difference in a post hoc t test (P < 0.05, two-tailed, Bonferroni corrected for multiple comparisons); SE, SE of mean; ECT, patients with electroconvulsive therapy; no-ECT, patients receiving only drug treatment.

Fig. 3.

Results of post hoc analyses. (A) Plots of the mean hippocampal, prefrontal, and subgenual GMV, changes (in percent) induced by ECT treatment compared with no-ECT patients and control subjects. (B) Correlation coefficients obtained between changes in subgenual (Left) and hippocampal (Right) GMV, and changes in the HDRS. Results are displayed separately for bipolar and unipolar depression patients subdivided by treatment condition (ECT vs. no-ECT). (C) Correlation coefficients between HDRS scores and subgenual (Left) and hippocampal (Right) GMV and the time point before and after ECT treatment, choosing suitable control periods in no-ECT patients. Results are displayed separately for bipolar (Upper) and unipolar (Lower) depression patients subdivided by treatment condition. An asterisk represents significant difference between the groups at a threshold of P < 0.05 (two-tailed, Bonferroni corrected).