Variations in myo-inositol in fronto-limbic regions and clinical response to electroconvulsive therapy in major depression

Abstract

Though electroconvulsive therapy (ECT) is an established treatment for severe depression, the neurobiological factors accounting for the clinical effects of ECT are largely unknown. Myo-inositol, a neurometabolite linked with glial activity, is reported as reduced in fronto-limbic regions in patients with depression. Whether changes in myo-inositol relate to the antidepressant effects of ECT is unknown. Using magnetic resonance spectroscopy ((1)H-MRS), we measured dorsomedial anterior cingulate cortex (dmACC) and left and right hippocampal myo-inositol in 50 ECT patients (mean age: 43.78, 14 SD) and 33 controls (mean age: 39.33, 12 SD) to determine cross sectional effects of diagnosis and longitudinal effects of ECT. Patients were scanned prior to treatment, after the second ECT and at completion of the ECT index series. Controls were scanned twice at intervals corresponding to patients' baseline and end of treatment scans. Myo-inositol increased over the course of ECT in the dmACC (p = 0.042). A significant hemisphere by clinical response effect was observed for the hippocampus (p = 0.003) where decreased myo-inositol related to symptom improvement in the left hippocampus. Cross-sectional differences between patients and controls at baseline were not detected. Changes in myo-inositol observed in the dmACC in association with ECT and in the hippocampus in association with ECT-related clinical response suggest the mechanisms of ECT could include gliogenesis or a reversal of gliosis that differentially affect dorsal and ventral limbic regions. Change in dmACC myo-inositol diverged from control values with ECT suggesting compensation, while hippocampal change suggested normalization.

Keywords: Depression; Electroconvulsive therapy (ECT); Mood Disorders; Single voxel magnetic resonance spectroscopy (MRS).

Figure 1

Sample voxel positioning and LC model output for the dorso-medial anterior cingulate and right hippocampus. Left hippocampus placement is not shown to avoid redundancy.

Figure 2

Graph of means show changes in CSF-adjusted ¹H-MRS myo-inositol concentration in the dorso-medial anterior cingulate for ECT patients scanned prior to treatment (T1), after two ECT sessions (T2) and at the end of the ECT index series (T3) and controls scanned twice (C1 and C2), corresponding to patient baseline and end of ECT index scans. AU indicates arbitrary units. Arrows and asterisks indicate significant changes in myo-inositol content for patients over the course of ECT. See text for p-values.

Figure 3

Scatter plots display changes in myo-inositol concentration and HAMD ratings over the course of ECT treatment (T3-T1) for the right and left hippocampus. Graph shows regression lines for both hippocampi.