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Although these disorders have traditionally been studied primarily from a neuronal perspective, accumulating evidence indicates that immune dysregulation and inflammatory processes play a central role in their pathophysiology. In this review, we advance the hypothesis that nitric oxide (NO)-mediated alterations in blood\u2013brain barrier (BBB) integrity represent a critical mechanistic link between inflammation and central nervous system dysfunction in neuropsychiatric disorders. NO is a gaseous multifunctional signaling molecule involved in vascular homeostasis and immune responses, and its dysregulated production, together with aberrant protein S-nitrosylation, has been implicated in several neuropsychiatric conditions. However, the specific mechanisms by which NO signaling contributes to BBB dysfunction remain incompletely defined. Here, we synthesize current evidence supporting a role for NO-dependent vascular and inflammatory pathways in BBB disruption and discuss how these processes may contribute to the onset and progression of neuropsychiatric conditions. Clarifying these mechanisms may provide novel insights into disease pathogenesis and identify therapeutic targets aimed at preserving BBB integrity and limiting neuroinflammation.<\/jats:p>","DOI":"10.3390\/ijms27083615","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T08:24:23Z","timestamp":1776673463000},"page":"3615","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Nitric Oxide-S-Nitrosylation and Its Role in Neuroinflammation Associated with Neuropsychiatric Conditions"],"prefix":"10.3390","volume":"27","author":[{"given":"Fabiola","family":"S\u00e1nchez","sequence":"first","affiliation":[{"name":"Instituto de Inmunolog\u00eda, Facultad de Medicina, Universidad Austral de Chile, Valdivia 5110566, Chile"},{"name":"Centro Interdisciplinario de Estudios del Sistema Nervioso (CISNe), Universidad Austral de Chile, Valdivia 5110566, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Koning","sequence":"additional","affiliation":[{"name":"Instituto de Alta Investigaci\u00f3n, Universidad de Tarapac\u00e1, Arica 1000000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"GBD 2019 Mental Disorders Collaborators (2022). 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