{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:25:22Z","timestamp":1787570722306,"version":"build-2736575974"},"reference-count":209,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:p>Neuroinflammatory mechanisms are increasingly recognized in biologically defined subgroups of psychiatric disorders, yet the cellular interfaces linking peripheral immune activation to brain dysfunction remain incompletely understood. This review examines the blood-brain barrier (BBB) and neurovascular unit (NVU) as dynamic immunometabolic structures whose stability depends on mitochondrial bioenergetics, redox signaling, calcium handling, mitophagy, and innate immune regulation. We integrate human postmortem, neuroimaging, cerebrospinal fluid and circulating biomarker findings with mechanistic evidence from cellular and animal models to examine whether mitochondrial dysfunction may be associated with BBB vulnerability, endothelial activation, altered tight-junction organization, and neuroinflammatory signaling. We discuss how this mitochondrial-BBB axis may contribute to transdiagnostic phenotypes such as cognitive impairment, anhedonia, fatigue, negative symptoms, affective dysregulation, and treatment resistance. Candidate biomarkers, including inflammatory mediators, BBB permeability markers, mitochondrial DNA, bioenergetic readouts, mitophagy markers, and neuroimaging measures, are considered as tools for patient stratification rather than diagnosis. Finally, we evaluate therapeutic implications, including mitochondrial-targeted interventions, BBB-protective strategies, anti-inflammatory approaches, metabolic modulation, and precision psychiatry frameworks. We argue that the mitochondrial regulation of BBB homeostasis represents a promising but still emerging framework for understanding neuroinflammatory psychiatric phenotypes and designing biomarker-guided studies.<\/jats:p>","DOI":"10.3389\/fnmol.2026.1924581","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:02:41Z","timestamp":1787569361000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial control of blood-brain barrier homeostasis in neuroinflammatory psychiatric disorders"],"prefix":"10.3389","volume":"19","author":[{"given":"Larli Misael","family":"P\u00e9rez-L\u00f3pez","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Autonomous University of Nuevo Le\u00f3n","place":["Monterrey, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Camacho-Morales","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Autonomous University of Nuevo Le\u00f3n","place":["Monterrey, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iv\u00f3n","family":"Howland-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Faculty of Health Sciences, Technical University of Manab\u00ed","place":["Portoviejo, Ecuador"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Al\u00ed","family":"P\u00e9rez-Maya","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Autonomous University of Nuevo Le\u00f3n","place":["Monterrey, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1017\/S003329172300140X","article-title":"Metabolomic profiles of 38 acylcarnitines in major depressive episodes before and after treatment.","volume":"54","author":"Ait Tayeb","year":"2024","journal-title":"Psychol. 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