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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author Neelabja Roy
Dhruva Ithal
Urvakhsh Meherwan Mehta
Rakshathi Basavaraju
Rose Dawn Bharath
Nicolas R. Bolo
Jagadisha Thirthalli
Bangalore N. Gangadhar
Matcheri S. Keshavan
author_facet Neelabja Roy
Dhruva Ithal
Urvakhsh Meherwan Mehta
Rakshathi Basavaraju
Rose Dawn Bharath
Nicolas R. Bolo
Jagadisha Thirthalli
Bangalore N. Gangadhar
Matcheri S. Keshavan
author_sort Neelabja Roy
collection DOAJ
description 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.
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spelling doaj-art-a147d2f80ee94c6fa569feaff6bb026b2025-08-20T03:09:44ZengElsevierBiological Psychiatry Global Open Science2667-17432025-07-015410049410.1016/j.bpsgos.2025.100494Putative Mechanisms of Electroconvulsive Therapy in Treatment-Resistant Schizophrenia Examined Using Magnetic Resonance ImagingNeelabja Roy0Dhruva Ithal1Urvakhsh Meherwan Mehta2Rakshathi Basavaraju3Rose Dawn Bharath4Nicolas R. Bolo5Jagadisha Thirthalli6Bangalore N. Gangadhar7Matcheri S. Keshavan8Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bangalore, IndiaDepartment of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bangalore, IndiaDepartment of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bangalore, India; Address correspondence to Urvakhsh Meherwan Mehta, M.D., Ph.D.Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bangalore, IndiaDepartment of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neuro Sciences, Bangalore, IndiaBeth Israel Deaconess Medical Center and Massachusetts Mental Health Center, Harvard Medical School, Boston, MassachusettsDepartment of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bangalore, IndiaDepartment of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bangalore, IndiaBeth Israel Deaconess Medical Center and Massachusetts Mental Health Center, Harvard Medical School, Boston, MassachusettsBackground: 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.http://www.sciencedirect.com/science/article/pii/S2667174325000485AmygdalaBrain connectivityBrain morphometryCerebellumPsychosis
spellingShingle Neelabja Roy
Dhruva Ithal
Urvakhsh Meherwan Mehta
Rakshathi Basavaraju
Rose Dawn Bharath
Nicolas R. Bolo
Jagadisha Thirthalli
Bangalore N. Gangadhar
Matcheri S. Keshavan
Putative Mechanisms of Electroconvulsive Therapy in Treatment-Resistant Schizophrenia Examined Using Magnetic Resonance Imaging
Biological Psychiatry Global Open Science
Amygdala
Brain connectivity
Brain morphometry
Cerebellum
Psychosis
title Putative Mechanisms of Electroconvulsive Therapy in Treatment-Resistant Schizophrenia Examined Using Magnetic Resonance Imaging
title_full Putative Mechanisms of Electroconvulsive Therapy in Treatment-Resistant Schizophrenia Examined Using Magnetic Resonance Imaging
title_fullStr Putative Mechanisms of Electroconvulsive Therapy in Treatment-Resistant Schizophrenia Examined Using Magnetic Resonance Imaging
title_full_unstemmed Putative Mechanisms of Electroconvulsive Therapy in Treatment-Resistant Schizophrenia Examined Using Magnetic Resonance Imaging
title_short Putative Mechanisms of Electroconvulsive Therapy in Treatment-Resistant Schizophrenia Examined Using Magnetic Resonance Imaging
title_sort putative mechanisms of electroconvulsive therapy in treatment resistant schizophrenia examined using magnetic resonance imaging
topic Amygdala
Brain connectivity
Brain morphometry
Cerebellum
Psychosis
url http://www.sciencedirect.com/science/article/pii/S2667174325000485
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