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Existing mechanistic accounts are biologically valid but are often presented as parallel lists: monoamine release, excitatory-inhibitory rebalancing, neuroendocrine activation, immune modulation, neurotrophic plasticity, hippocampal change, and network rewiring. We propose the postictal systems window hypothesis. The organizing principle is seizure-induced postictal recoupling: the therapeutic seizure interrupts a rigid depressive state, whereas the subsequent recovery phase couples electrophysiological, neurovascular-metabolic, clinical, endocrine, and immune-metabolic dynamics. The central claim is not that ECT affects every biological domain. The claim is that an adequate seizure triggers a timed postictal state in which a smaller set of core events - postictal network interruption and recovery, a structured hemodynamic-metabolic transition, and early clinical reorientation - becomes coupled to endocrine and immune-metabolic signaling and later consolidation. This hierarchy is critical. Neurovascular coupling and hemodynamic waves are treated as core components of the postictal transition; blood-brain barrier and neurovascular-unit permeability are treated as plausible but second-order interfaces, not established human mediators. Glial, trophic, structural, and epigenetic changes are placed mainly downstream as translation and consolidation mechanisms. Recent optical neuroimaging evidence that ECT seizures are followed by hyperemic waves consistent with cortical spreading depolarization supports the principle that the postictal period contains organized biological events rather than simple seizure termination. The model is falsifiable: early postictal curves after the first one to three treatments should predict remission and cognitive burden better as a prespecified composite than as isolated markers such as seizure duration, postictal suppression, cortisol, C-reactive protein, or brain-derived neurotrophic factor. Cognitive adverse effects should relate to excessive duration, delayed recovery, or medial temporal exposure of the window rather than to antidepressant efficacy itself.<\/jats:p>","DOI":"10.3389\/fpsyt.2026.1889207","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T05:54:51Z","timestamp":1786514091000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The postictal systems window hypothesis of electroconvulsive therapy in major depression"],"prefix":"10.3389","volume":"17","author":[{"given":"Bernard","family":"Rybczynski","sequence":"first","affiliation":[{"name":"6th Department of Psychiatry, Mazovian Specialist Health Centre in Pruszkow","place":["Pruszkow, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Maslyk","sequence":"additional","affiliation":[{"name":"Institute of Biological Sciences, The John Paul II Catholic University of Lublin","place":["Lublin, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bartosz Wojciech","family":"Maj","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Health Center of Tomaszow Mazowiecki","place":["Tomaszow Mazowiecki, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Pruc","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, The John Paul II Catholic University of Lublin","place":["Lublin, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iwona","family":"Niewiadomska","sequence":"additional","affiliation":[{"name":"Institute of Psychology, The John Paul II Catholic University of Lublin","place":["Lublin, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukasz","family":"Szarpak","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, The John Paul II Catholic University of Lublin","place":["Lublin, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2034954","article-title":"Electroconvulsive therapy","volume":"386","author":"Espinoza","year":"2022","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/acps.13054","article-title":"Improvement after two sessions of electroconvulsive therapy predicts final remission in in-patients with major depression","volume":"140","author":"Birkenhager","year":"2019","journal-title":"Acta Psychiatr Scand"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/acps.13134","article-title":"When to consider electroconvulsive therapy (ECT)","volume":"141","author":"Kellner","year":"2020","journal-title":"Acta Psychiatr Scand"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/7854_2023_450","article-title":"Mechanism of action of ECT in depression","volume":"66","author":"Belge","year":"2024","journal-title":"Curr Top Behav Neurosci"},{"key":"B5","volume-title":"The Management of Major Depressive Disorder. 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