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Hippocampal microstructural changes following electroconvulsive therapy in severe depression

Molecular Psychiatry volume 30, pages 4343–4352 (2025)Cite this article

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Abstract

Electroconvulsive therapy (ECT) induces hippocampal volume increases in depressed patients, potentially reflecting neuroplasticity. We hypothesized that Neurite Orientation Dispersion and Density Imaging (NODDI) could provide in vivo evidence of hippocampal neuroplasticity following ECT. This longitudinal study evaluated 43 depressed patients undergoing ECT and 24 controls. MRI and clinical assessments were performed at baseline (V1), after 5 sessions (V2), and post-treatment (V3). Evaluations included a 3 T MR-scan with 3DT1-weighted and multi-shell diffusion (b = 200/1500/2500 s/mm², 30/45/60directions) sequences. Q-ball, Diffusion Tensor, and NODDI models provided: axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD), fractional anisotropy (FA), generalized FA (GFA), neurite density index (NDI), isotropic fraction (Fiso), and orientation dispersion index (ODI). FreeSurfer extracted whole hippocampal and subfield volumes from T1-weighted images. Longitudinal changes were assessed with linear mixed-effect models. 107 MRIs from patients and 24 MRIs from controls were analyzed. ECT induced significant bilateral hippocampal volume increases (p < 0.001). Group comparisons showed consistently higher FA, lower GFA and ODI in patients compared to controls at all time-points. Following ECT, significant diffusion changes included decreased hippocampal GFA, FA, AD, MD and Fiso, along with increased ODI and NDI. NDI and Fiso changes were localized to the dentate gyrus but not the hippocampal tail. ECT responders showed a significant right hippocampal volume increase at V2 compared to non-responders. After ECT, hippocampal volume increases are accompanied by bilateral changes in NODDI parameters, particularly in the dentate gyrus, consistent with hippocampal neuroplasticity.

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Fig. 1: Image processing steps of the 3D T1-w and diffusion-weighted data.
Fig. 2: Volumes of the whole hippocampus, dentate gyrus, and hippocampal tail over time in depressed patients across three time points and in healthy controls.
Fig. 3: Changes in whole Hippocampus DTI metrics over time in depressed patients across three time points and in healthy controls.
Fig. 4: Changes in whole Hippocampus NODDI metrics over time in depressed patients across three time points and in healthy controls.
Fig. 5: Early hippocampal volumetric changes in responders vs. non-responders to ECT.

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Data availability

The dataset analyzed during the current study are not publicly available but are available from the corresponding author upon motivated request.

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Acknowledgements

We thank the patients for their trust and commitment in making this clinical trial possible. We thank all the nursing and administrative staff who devoted time and effort to the success of this research project, in particular Bénédicte Launay-Saucet, the clinical trial nurse coordinator. The clinical trial was sponsored by the Groupe Hospitalier Universitaire Paris Psychiatrie et Neurosciences and its Delegation for Clinical Research and Innovation; we thank Viviane Awassi, Kenza Sabi, Khaoussou Sylla and Marin Chapelle. This work was supported and funded by the Groupe Hospitalier Universitaire Paris Psychiatrie et Neurosciences (‘Appel à projets 2017’) and the Fondation de France (‘AO 2017 sur les maladies psychiatriques’). We thank Denis David and Jean-Philippe Guilloux for fruitful discussions. Finally, we thank the reviewers for their significant contributions, which helped to improve this work.

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Author notes

  1. These authors contributed equally: A. Le Berre, D. Attali.

  2. These authors jointly supervised this work: C. Oppenheim, M. Plaze.

Authors and Affiliations

  1. Université Paris Cité, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Ima-Brain team, 75014, Paris, France

    A. Le Berre, C. Debacker, M. Lui, S. Charron, M. Moyal, F. Ramon, A. Henensal, J. Benzakoun, P. Gorwood, A. Cachia, C. Oppenheim & M. Plaze

  2. GHU-Paris Psychiatrie et Neurosciences, Hôpital Sainte Anne, F-75014, Paris, France

    A. Le Berre, D. Attali, C. Debacker, M. Lui, S. Charron, M. Moyal, A. Henensal, J. Benzakoun, L. Mekaoui, P. Gorwood, C. Oppenheim & M. Plaze

  3. Physics for Medicine Paris, Inserm U1273, CNRS UMR 8063, ESPCI Paris, PSL University, Paris, France

    D. Attali

  4. BAOBAB, UMR 9027, NeuroSpin, Université Paris-Saclay, CNRS, CEA, Gif-sur-Yvette, France

    I. Uszynski & C. Poupon

  5. Université Paris Cité, Laboratory for the Psychology of Child Development and Education, CNRS UMR 8240, F-75005, Paris, France

    A. Cachia

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Contributions

DA and MP contributed to the conception and design of the study. DA, MP, CD, SC, LM, PG, ML, CO contributed to clinical and MRI data acquisition. IU and CP provided methodological development. ALB, IU, CD, CP, AC, FR conducted MRI data preprocessing and statistical data analysis. ALB, DA, MP, AC, CO conducted the interpretation of the analyses with additional contributions from MM and AH. DA, MP, ML, CD, SC provided administrative, technical, and material support. ALB drafted the manuscript. CO, AC and MP supervised the study and critically revised the manuscript. All authors reviewed and approved the final version of the manuscript.

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Correspondence to A. Le Berre.

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Le Berre, A., Attali, D., Uszynski, I. et al. Hippocampal microstructural changes following electroconvulsive therapy in severe depression. Mol Psychiatry 30, 4343–4352 (2025). https://doi.org/10.1038/s41380-025-03016-x

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