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Subcallosal cingulate (SCC) activity is associated with treatment response in major depressive disorder (MDD). Using electroconvulsive therapy (ECT) as a treatment model in this exploratory study, we addressed whether pretreatment SCC structural connectivity with corticolimbic-striatal circuitry relates to therapeutic outcome and whether these connectivity patterns change with treatment.Diffusion magnetic resonance imaging scans were acquired in 43 patients with MDD (mean [SD] age = 41 [13] years; men/women: 18/25) before and within 1 week of completing an ECT index series and in 31 healthy control subjects scanned twice (mean [SD] age = 38 [11] years; men/women: 17/18). Probabilistic tractography from subject-specific anatomically defined SCC seed regions to the ventral striatum (VS), anterior cingulate cortex (ACC), and bilateral medial prefrontal cortex (mPFC) was used to estimate structural connectivity in the target network.SCC-mPFC connectivity was lower in responders (50% symptom improvement) than nonresponders both before (p.014) (difference 37%-96% left and right hemispheres) and after (p = .023) (difference 100% right hemisphere) treatment. SCC-mPFC connectivity in responders was also decreased compared with control subjects both at baseline (p = .012) and after ECT (p = .006), whereas nonresponders had SCC-right mPFC connectivity similar to that of control subjects. Subjects with MDD also showed decreased SCC-ACC connectivity compared with control subjects (baseline: p.003, after ECT: p = .001), although SCC-ACC connectivity did not distinguish responders from nonresponders. Bilateral SCC-VS connectivity decreased (11%) with ECT (p = .021) regardless of treatment response.While SCC-ACC connectivity may be a hallmark of MDD compared with control subjects, lower pretreatment SCC-mPFC connectivity in ECT responders (compared with nonresponders and control subjects) suggests that connectivity in this pathway may serve as a potential biomarker of therapeutic outcome and be relevant for treatment selection.

Electroconvulsive therapy (ECT) is an effective treatment for severe depression and is shown to increase hippocampal volume and modulate hippocampal functional connectivity. Whether variations in hippocampal structural connectivity occur with ECT and relate to clinical response is unknown.Patients with major depression (n = 36, 20 women, age 41.49 ± 13.57 years) underwent diffusion magnetic resonance imaging at baseline and after ECT. Control subjects (n = 32, 17 women, age 39.34 ± 12.27 years) underwent scanning twice. Functionally defined seeds in the left and right anterior hippocampus and probabilistic tractography were used to extract tract volume and diffusion metrics (fractional anisotropy and axial, radial, and mean diffusivity). Statistical analyses determined effects of ECT and time-by-response group interactions (50% change in symptoms before and after ECT defined response). Differences between baseline measures across diagnostic groups and in association with treatment outcome were also examined.Significant effects of ECT (all p.01) and time-by-response group interactions (all p.04) were observed for axial, radial, and mean diffusivity for right, but not left, hippocampal pathways. Follow-up analyses showed that ECT-related changes occurred in responders only (all p.01) as well as in relation to change in mood examined continuously (all p.004). Baseline measures did not relate to symptom change or differ between patients and control subjects. All measures remained stable across time in control subjects. No significant effects were observed for fractional anisotropy and volume.Structural connectivity of hippocampal neural circuits changed with ECT and distinguished treatment responders. The findings suggested neurotrophic, glial, or inflammatory response mechanisms affecting axonal integrity.