{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T08:58:09Z","timestamp":1781254689072,"version":"3.54.1"},"posted":{"date-parts":[[2026,6,9]]},"group-title":"Neuroscience","reference-count":74,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Epilepsy is characterized by widespread structural brain alterations extending beyond the epileptic zone, involving both cortical and subcortical regions. Importantly, the clinical manifestation of epilepsy, including seizure types, psychiatric comorbidities, and treatment responses, has been shown to differ between sexes. However, sex differences in structural alterations in epilepsy have been seldomly reported in neuroimaging studies, partly due to limited sample sizes and single-center designs. Here, we systematically investigated sex differences in common epilepsies and their related clinical variables using structural neuroimaging biomarkers in an international multi-center cohort of 1,253 epilepsy patients and 1,077 healthy controls. We studied cortical thickness and subcortical volume in two types of epilepsy: temporal lobe epilepsy (TLE) and genetic generalized epilepsy (GGE). Both male and female patients with TLE showed widespread cortical and subcortical thinning compared with controls. In GGE, when compared separately to controls, male patients showed only subtle structural alterations, whereas female patients exhibited more widespread structural alterations. Sex-stratified analyses revealed some variation in the extent and distribution of cortical thickness and subcortical volume alterations between male and female patients in both epilepsy cohorts. Yet, we did not find significant sex-by-diagnosis interaction effects in TLE and GGE. Similarly, no significant interaction effects were observed between sex and age of onset or disease duration in either patient group. Overall, although we observed some differences in regional cortical thickness and subcortical volume between male and female patients with epilepsy, we did not find significant sex-by-diagnosis interactions. Our findings indicate that sex differences in behavioral and clinical outcomes of epilepsy may involve biological or functional processes that require further investigation.<\/jats:p>","DOI":"10.64898\/2026.06.06.730611","type":"posted-content","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T21:55:13Z","timestamp":1781042113000},"source":"Crossref","is-referenced-by-count":0,"title":["Sex-related structural alterations across common epilepsies: a worldwide ENIGMA study"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3983-2270","authenticated-orcid":false,"given":"Huantao","family":"Wen","sequence":"first","affiliation":[{"name":"Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany"},{"name":"Institute of Neuroscience and Medicine (INM-7: Brain and Behaviour), Research Center J\u00fclich, J\u00fclich, Germany"},{"name":"Faculty of Life Science, Leipzig University, Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9077-3354","authenticated-orcid":false,"given":"Bin","family":"Wan","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany"},{"name":"Institute of Neuroscience and Medicine (INM-7: Brain and Behaviour), Research Center J\u00fclich, J\u00fclich, Germany"},{"name":"Department of Psychiatry, University Hospitals of Gen\u00e8ve, Thonex, Switzerland"},{"name":"Synapsy Center for Neuroscience and Mental Health Research, University of Gen\u00e8ve, Gen\u00e8ve, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taha","family":"Gholipour","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, 9300 Campus Point Drive, #7740, La Jolla, 92037, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7101-2493","authenticated-orcid":false,"given":"Ke","family":"Xie","sequence":"additional","affiliation":[{"name":"Centre for Excellence in Epilepsy at the Neuro (CEEN) and McConnell Brain Imaging Centre (BIC), Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy","family":"Chen","sequence":"additional","affiliation":[{"name":"Centre for Excellence in Epilepsy at the Neuro (CEEN) and McConnell Brain Imaging Centre (BIC), Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Serio","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany"},{"name":"Institute of Neuroscience and Medicine (INM-7: Brain and Behaviour), Research Center J\u00fclich, J\u00fclich, Germany"},{"name":"Max Planck School of Cognition, Leipzig, Germany"},{"name":"Institute of Systems Neuroscience, Heinrich Heine University D\u00fcsseldorf, D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meike D.","family":"Hettwer","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany"},{"name":"Institute of Neuroscience and Medicine (INM-7: Brain and Behaviour), Research Center J\u00fclich, J\u00fclich, Germany"},{"name":"Penn Lifespan Informatics & Neuroimaging Center, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina K.M.","family":"Alvim","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Campinas-UNICAMP, Rua Tessalia Vieira de Camargo 126, Campinas, 13083-887, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatello","family":"Arienzo","sequence":"additional","affiliation":[{"name":"Department of Radiation Medicine and Applied Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, 92093, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael Batista","family":"Jo\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Campinas-UNICAMP, Rua Tessalia Vieira de Camargo 126, Campinas, 13083-887, SP, Brazil"},{"name":"Brazilian Institute of Neuroscience and Neurotechnology, Rua Vital Brasil 251, Campinas, 13083888, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Bauer","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany"},{"name":"Department of Epileptology, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), Venusberg-Campus 1, Bonn, 53127, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Bernasconi","sequence":"additional","affiliation":[{"name":"Centre for Excellence in Epilepsy at the Neuro (CEEN) and McConnell Brain Imaging Centre (BIC), Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada"},{"name":"Neuroimaging of Epilepsy Laboratory, Montreal Neurological Institute, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neda","family":"Bernasconi","sequence":"additional","affiliation":[{"name":"Centre for Excellence in Epilepsy at the Neuro (CEEN) and McConnell Brain Imaging Centre (BIC), Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada"},{"name":"Neuroimaging of Epilepsy Laboratory, Montreal Neurological Institute, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Bonanni","sequence":"additional","affiliation":[{"name":"Scientific Institute IRCCS E.Medea, Epilepsy and Clinical Neurophysiology Unit, Conegliano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Eugenia","family":"Caligiuri","sequence":"additional","affiliation":[{"name":"Neuroscience Research Center, Department of Medical and Surgical Sciences, University \u201cMagna Gr\u00e6cia\" of Catanzaro, Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Cendes","sequence":"additional","affiliation":[{"name":"Brazilian Institute of Neuroscience and Neurotechnology, Rua Vital Brasil 251, Campinas, 13083888, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rapha\u00ebl","family":"Christin","sequence":"additional","affiliation":[{"name":"Department of 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2307-071X","authenticated-orcid":false,"given":"Marian","family":"Galovic","sequence":"additional","affiliation":[{"name":"Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Frauenklinikstrasse 26, Zurich, 8091, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Gambardella","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Institute of Neurology, Magna Graecia University, Viale Europa, Catanzaro, 88100, Calabria, Italy"},{"name":"Neuroscience Research Center, Magna Graecia University, Viale Europa, Catanzaro, 88100, Calabria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renzo","family":"Guerrini","sequence":"additional","affiliation":[{"name":"Neuroscience and Human Genetics Department, Meyer Children\u2019s Hospital IRCCS, 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Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlo","family":"Naish","sequence":"additional","affiliation":[{"name":"Centre for Excellence in Epilepsy at the Neuro (CEEN) and McConnell Brain Imaging Centre (BIC), Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8999-9388","authenticated-orcid":false,"given":"Alexander","family":"Ngo","sequence":"additional","affiliation":[{"name":"Centre for Excellence in Epilepsy at the Neuro (CEEN) and McConnell Brain Imaging Centre (BIC), Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terence J.","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, School of Translational Medicine, The Alfred Hospital, Monash University, 99 Commercial Road, 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