{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:22:59Z","timestamp":1787023379820,"version":"build-2736575974"},"reference-count":0,"publisher":"Association of Basic Medical Sciences of FBIH","issue":"2","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomol Biomed"],"abstract":"<jats:p>Post-traumatic stress disorder (PTSD) is a multidimensional illness that seldom occurs alone: roughly 80 % of patients also meet criteria for anxiety, depression, chronic pain, substance-use, eating or cognitive disorders. Converging genetic, neurochemical and behavioural findings implicate the neuropeptide S (NPS) system\u2014acting through its G-protein-coupled NPS receptor (NPSR)\u2014as a common regulator of these diverse phenotypes. This narrative review surveys studies published 2000\u20132024 in PubMed, Embase and Web of Science that examine NPS\/NPSR involvement in core PTSD features and typical comorbidities.\u00a0The functional rs324981 A\/T polymorphism, which boosts NPSR surface expression and signalling, consistently associates with greater PTSD risk and symptom severity. In rodent models, exogenous NPS reduces anxiety- and fear-like behaviours, speeds fear-memory extinction, stabilises the hypothalamic-pituitary-adrenal axis, enhances dopaminergic tone and elevates hippocampal brain-derived neurotrophic factor (BDNF)\u2014changes concordant with symptom relief. Additional work shows that NPS lessens pain affect, dampens alcohol and opioid intake, eases withdrawal-induced anxiety and lowers food consumption, hinting at a multimodal therapeutic profile. These effects converge on limbic and mid-brain circuits (amygdala, ventral tegmental area, locus coeruleus, paraventricular nucleus) and engage oxytocinergic, adenosinergic and endocannabinoid pathways.\u00a0Translation remains limited by NPS\u2019s rapid degradation, poor blood\u2013brain-barrier penetration and scarcity of brain-penetrant NPSR ligands, but advances in intranasal delivery, lipid-acylated analogues, biased NPSR agonists and \u201chumanised\u201d NPSR-variant models offer promising solutions. Collectively, current pre-clinical and genetic evidence positions the NPS\u2013NPSR axis as a versatile therapeutic target for both core PTSD symptoms and their disabling comorbidities, warranting rigorous translational studies to refine mechanism, optimise drug-like properties and test clinical efficacy.<\/jats:p>","DOI":"10.17305\/bb.2025.12861","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T22:00:39Z","timestamp":1754344839000},"page":"227-239","source":"Crossref","is-referenced-by-count":1,"title":["Neuropeptide S pathway in PTSD and neuropsychiatric disorders: A review"],"prefix":"10.17305","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7036-7227","authenticated-orcid":false,"given":"Zhi-cheng","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-jing","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-yang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang-min","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0773-0124","authenticated-orcid":false,"given":"Fei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"6922","published-online":{"date-parts":[[2025,8,4]]},"container-title":["Biomolecules and Biomedicine"],"original-title":[],"link":[{"URL":"https:\/\/bjbms.org\/ojs\/index.php\/bjbms\/article\/download\/12861\/3978","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bjbms.org\/ojs\/index.php\/bjbms\/article\/download\/12861\/3978","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T22:02:33Z","timestamp":1759183353000},"score":1,"resource":{"primary":{"URL":"https:\/\/bjbms.org\/ojs\/index.php\/bjbms\/article\/view\/12861"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,4]]},"references-count":0,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,9,29]]}},"URL":"https:\/\/doi.org\/10.17305\/bb.2025.12861","relation":{},"ISSN":["2831-090X","2831-0896"],"issn-type":[{"value":"2831-090X","type":"electronic"},{"value":"2831-0896","type":"print"}],"subject":[],"published":{"date-parts":[[2025,8,4]]}}}