{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T04:29:41Z","timestamp":1786681781385,"version":"build-2736575974"},"reference-count":121,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Perioperative neurocognitive disorders (PND) encompass a spectrum of cognitive impairments occurring across the surgical period and are associated with significant morbidity, delayed recovery, and reduced quality of life. Although established risk factors include advanced age, cardiovascular disease, and preexisting cognitive impairment, the contribution of mood disorders to PND susceptibility remains incompletely understood. This review systematically examines the neurobiological overlap between mood disorders, particularly major depressive disorder (MDD) and bipolar disorder, and PND, with emphasis on shared biomolecular mechanisms. We identify convergent pathophysiologic pathways including hypothalamic\u2013pituitary\u2013adrenal (HPA) axis dysregulation, chronic neuroinflammation, NF-\u03baB-mediated cytokine signaling, microglial priming, tryptophan\u2013kynurenine pathway dysregulation, and brain-derived neurotrophic factor (BDNF) suppression. These mechanisms collectively suggest that patients with preexisting mood disorders may enter surgery in a biologically sensitized neuroimmune state, lowering the threshold for exaggerated neuroinflammatory responses and postoperative cognitive dysfunction. Recognition of mood disorders as modifiable perioperative vulnerability states may inform preoperative risk stratification, guide anesthetic and analgesic management, and support the development of targeted interventions to reduce postoperative cognitive complications and improve surgical outcomes.<\/jats:p>","DOI":"10.3390\/biom16081179","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T12:53:48Z","timestamp":1786539228000},"page":"1179","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular and Cellular Mechanisms Linking Mood Disorders, HPA Axis Dysregulation, and Neurocognitive Inflammation to Perioperative Neurocognitive Disorders"],"prefix":"10.3390","volume":"16","author":[{"given":"Alyson","family":"Sato","sequence":"first","affiliation":[{"name":"University of Illinois College of Medicine, Chicago Campus, Chicago, IL 60612, USA"},{"name":"Department of Anesthesiology, University of Illinois, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1542-1652","authenticated-orcid":false,"given":"Nicole","family":"Chang","sequence":"additional","affiliation":[{"name":"University of Illinois College of Medicine, Chicago Campus, Chicago, IL 60612, USA"},{"name":"Department of Anesthesiology, University of Illinois, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8028-1495","authenticated-orcid":false,"given":"Nebojsa Nick","family":"Knezevic","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Illinois, Chicago, IL 60612, USA"},{"name":"Department of Anesthesiology, Advocate Illinois Masonic, Chicago, IL 60657, USA"},{"name":"Department of Surgery, University of Illinois, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanannait","family":"Paisansathan","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1111\/cns.13873","article-title":"Perioperative Neurocognitive Disorders: A Narrative Review Focusing on Diagnosis, Prevention, and Treatment","volume":"28","author":"Kong","year":"2022","journal-title":"CNS Neurosci. 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