557. ECT-induced effects on brain structure, brain connectivity and cerebrospinal-fluid-based markers – a preliminary analysis

Abstract

Abstract Background Electroconvulsive therapy (ECT) is among the most effective treatments for severe and treatment-resistant depression. Despite more than 90 years of clinical use, its underlying neurobiological mechanisms remain incompletely understood. One prominent hypothesis suggests that ECT induces neuroplastic changes, supported by evidence of volumetric brain alterations in regions implicated in depression and increases in peripheral neurotrophins [1,2]. In contrast, critical perspectives interpret post-ECT volumetric changes as transient oedema or raise concerns about potential neuronal damage. Aims & Objectives The present prospective study aimed to investigate ECT-associated changes in brain structure and functional connectivity using magnetic resonance imaging (MRI), alongside cerebrospinal fluid (CSF) markers of neuronal and glial injury, in patients with severe depression. Method Thirteen hospitalized patients with treatment-resistant depression (mean age 41 ± 9.6 years; baseline Hamilton Depression Rating Scale (HAMD17) score 26 ± 3.1, indicating severe depression) underwent a course of eight bilateral ECT sessions. ECT was administered using a Thymatron IV device under general anesthesia with either methohexital or ketofol and succinylcholine as muscle relaxant; stimulus dosing was determined via individual seizure threshold titration. All patients remained on stable antidepressant medication throughout the treatment period. Structural and resting-state MRI scans were acquired before the first and after the eighth ECT session using a Siemens MAGNETOM Prisma 3T scanner, accompanied by lumbar puncture at both time points. Gray matter volume changes were assessed using a repeated-measures analysis of covariance (rmANCOVA) with age and sex as covariates. Brain segmentation was performed with FreeSurfer 7.1, and statistical analyses were conducted using SPSS Version 25. Resting-state functional connectivity analyses focused on the default mode network (DMN) as a seed region, with preprocessing performed in SPM12. CSF concentrations of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were quantified using single molecule array (SIMOA) technology, with statistical analyses conducted in RStudio. Given the exploratory nature of the study, results are reported without correction for multiple comparisons. Results Following ECT, depressive symptoms significantly improved, as reflected by a marked reduction in HAMD17 scores (t = 6.1, p < 0.001). Structural MRI revealed a significant, uncorrected increase in gray matter volume confined to the left precuneus (F = 6.016, p = 0.044). Functional connectivity analyses demonstrated reduced connectivity between the DMN and the cerebellum (t = 6.61, p < 0.001) as well as the middle occipital gyrus (t = 5.85, p = 0.002) following ECT. Importantly, no significant changes in CSF levels of NfL (p = 0.213) or GFAP (p = 0.362) were observed. Discussion & Conclusions Consistent with previous neuroimaging findings, ECT was associated with alterations in brain structure and DMN connectivity – a network critically involved in the pathophysiology of depression [3]. Notably, the absence of changes in CSF markers of neuronal or glial injury provides no evidence for ECT-related neuronal damage in this cohort. Whether the observed neuroimaging changes represent a necessary component of ECT’s antidepressant efficacy remains an open question. The small sample size and exploratory design constitute important limitations and warrant replication in larger, controlled studies.