Putative Mechanisms of Electroconvulsive Therapy in Treatment-Resistant Schizophrenia Examined Using Magnetic Resonance Imaging

Background: The neural mechanisms of electroconvulsive therapy (ECT) in refractory schizophrenia remain elusive. In the current study, we aimed to identify magnetic resonance imaging (MRI)–derived structural (cortical/subcortical volumes) and functional (resting-state connectivity) brain changes aft...

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Main Authors: Neelabja Roy, Dhruva Ithal, Urvakhsh Meherwan Mehta, Rakshathi Basavaraju, Rose Dawn Bharath, Nicolas R. Bolo, Jagadisha Thirthalli, Bangalore N. Gangadhar, Matcheri S. Keshavan
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Biological Psychiatry Global Open Science
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Online Access:http://www.sciencedirect.com/science/article/pii/S2667174325000485
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Summary:Background: The neural mechanisms of electroconvulsive therapy (ECT) in refractory schizophrenia remain elusive. In the current study, we aimed to identify magnetic resonance imaging (MRI)–derived structural (cortical/subcortical volumes) and functional (resting-state connectivity) brain changes after ECT and their associations with clinical response. Methods: We used an inductive (whole-brain, hypothesis-free) approach to examine structural and functional brain changes and their association with clinical response (positive symptom reduction) in clozapine-refractory schizophrenia (n = 30) after ECT (median 8 sessions). Furthermore, a deductive approach was used to compare baseline whole-brain MRI data from clozapine-refractory patients (n = 31) to data from clozapine responders (n = 23), thereby identifying regions of interest unique to clozapine-refractory schizophrenia. Changes in these regions of interest post-ECT and their association with clinical response were then examined. Results: The inductive approach identified volumetric enhancement in the bilateral amygdalae (Cohen’s d = 0.4), which was significantly associated with clinical response (β = −0.01, p = .003). The deductive approach identified posterior cerebellar hyperconnectivity as being unique to clozapine-refractory schizophrenia (d = 1.57), which was associated with baseline positive symptoms (r = 0.36, p = .04). Following ECT, there was a significant reduction in posterior cerebellar hyperconnectivity (d = −0.86), and this reduction was significantly associated with clinical response (β = 0.42, p = .002). Increased hippocampal and frontal volumes, frontoparietal connectivity, and reduced sensorimotor connectivity were also observed but were unrelated to clinical response. Conclusions: ECT may drive clinical improvement in refractory schizophrenia by increasing amygdala volumes and reducing posterior cerebellar connectivity. Randomized sham-controlled trials can confirm these findings in the future.
ISSN:2667-1743