Structural Connectivity Correlates of Response to Electroconvulsive Therapy in Treatment-Resistant Depression

Samman, M. E.; Fiorentini, L.; Fazzito, M. L.; Herlyn, D. L.; Tsuchiyagaito, A.; Castro, M. N.; Costanzo, E.; Camprodon, J. A.; Forcato, C.; Guinjoan, S. M.; Villarreal, M. F.

doi:10.1101/2025.03.18.643974

bioRxiv · 10.1101/2025.03.18.643974

Structural Connectivity Correlates of Response to Electroconvulsive Therapy in Treatment-Resistant Depression

Samman, M. E.·Fiorentini, L.·Fazzito, M. L.·Herlyn, D. L.·Tsuchiyagaito, A.·Castro, M. N.·Costanzo, E.·Camprodon, J. A.·Forcato, C.·Guinjoan, S. M.·Villarreal, M. F.

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Abstract

BackgroundElectroconvulsive therapy (ECT) is the most effective option for treatment resistant depression (TRD). In this study, we sought to explore if structural connectivity of limbic networks has an association with response to ECT. MethodsWe studied 23 patients with TRD who underwent a course of bifrontal ECT, employing probabilistic tractography at baseline to assess structural connectivity between the thalamus (THA), posterior (PCC), subgenual cingulate cortices, anterior insula (aINS), amygdala and orbitofrontal and ventrolateral prefrontal cortices, hypothesizing that these hubs participate in the formation and refractoriness of depression symptoms. We also include 21 healthy subject as controls group (HC). ResultsConnectivity between left THA and left PCC was related to both baseline depression severity (R=0.504; p= 0.017) and clinical response (R=0.452; p=0.004). Right aINS-prefrontal connectivity was associated with less clinical response. Structural connectivity was globally higher in patients than in HC (F=2.488; p=0.007). ConclusionsThe association of ECT response with stronger structural connectivity between hubs supporting self-referential bodily experience as well as autobiographical memory encoding and retrieval deserves exploration as a predictor in persons with TRD. In turn, the right aINS is a major hub for the salience network and is involved in repetitive negative mentation. Stronger structural connectivity of this region may be a heuristically valid biomarker for refractory TRD. We discuss the potential of the present findings for the design of anatomically precise neuromodulation interventions that would be useful to treat TRD while circumventing cognitive side effects of ECT.

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Samman, M. E., Fiorentini, L., Fazzito, M. L., Herlyn, D. L., Tsuchiyagaito, A., Castro, M. N., Costanzo, E., Camprodon, J. A., Forcato, C., Guinjoan, S. M., Villarreal, M. F.. 2025-03-19. Structural Connectivity Correlates of Response to Electroconvulsive Therapy in Treatment-Resistant Depression. https://doi.org/10.1101/2025.03.18.643974

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