Hippocampal volume trajectory and its relation to clinical course during and following ECT-treatment in patients with depression: A systematic review and meta-analysis

BACKGROUND: Neuroimaging studies in humans and translational animal models consistently demonstrate ECT-induced hippocampal volume increases. However, evidence linking hippocampal volume changes to clinical improvement in depression has been inconsistent. This systematic review with meta-analysis extends previous work to investigate whether hippocampal volume changes following the completion of an ECT-index series are associated with the clinical course of depression. METHODS: We conducted a systematic review and meta-analysis following PRISMA guidelines. Studies were eligible if they assessed hippocampal volume and included at least three imaging timepoints, with two performed after completion of the ECT-index series (t1 = pre-ECT, t2 = post-ECT, t3 = follow-up). Standardized mean change (SMC) was calculated for hippocampal volume and depressive symptom severity across timepoints. Pooled estimates were derived using random-effects models with restricted maximum likelihood (REML) estimation to account for between-study heterogeneity. Meta-regression analyses were performed to evaluate associations between volumetric changes and trajectories of depressive symptoms post-ECT. RESULTS: Fifteen studies (N = 447 patients) were included in the systematic review, with six studies (N = 151 patients) contributing complete volumetric data for meta-analysis. Hippocampal volumes increased significantly from t1 to t2 and largely returned to baseline at t3. Depression severity decreased substantially from t1 to t2 and remained stable at follow-up. Meta-regression analyses indicated no significant associations between changes of hippocampal volume and depressive symptoms from post-ECT to follow-up. Sensitivity analyses confirmed robustness of the findings. CONCLUSIONS: Hippocampal volume increases following ECT are transient and not associated with the clinical course of depression.