Neuropeptide S pathway in PTSD and neuropsychiatric disorders: A review
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 neu...
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Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina
2025-08-01
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| Series: | Biomolecules & Biomedicine |
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| Online Access: | https://www.bjbms.org/ojs/index.php/bjbms/article/view/12861 |
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| author | Zhi-cheng Zhu Xue-jing Han Zhen He Meng-yang Liu Ning Wu Xiang-min Tong Fei Li |
| author_facet | Zhi-cheng Zhu Xue-jing Han Zhen He Meng-yang Liu Ning Wu Xiang-min Tong Fei Li |
| author_sort | Zhi-cheng Zhu |
| collection | DOAJ |
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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—acting through its G-protein-coupled NPS receptor (NPSR)—as a common regulator of these diverse phenotypes. This narrative review surveys studies published 2000–2024 in PubMed, Embase and Web of Science that examine NPS/NPSR involvement in core PTSD features and typical comorbidities. The 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)—changes 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. Translation remains limited by NPS’s rapid degradation, poor blood–brain-barrier penetration and scarcity of brain-penetrant NPSR ligands, but advances in intranasal delivery, lipid-acylated analogues, biased NPSR agonists and “humanised” NPSR-variant models offer promising solutions. Collectively, current pre-clinical and genetic evidence positions the NPS–NPSR 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.
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| format | Article |
| id | doaj-art-5ebe2856646b4db9bc90d03cc97b2067 |
| institution | Kabale University |
| issn | 2831-0896 2831-090X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina |
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| series | Biomolecules & Biomedicine |
| spelling | doaj-art-5ebe2856646b4db9bc90d03cc97b20672025-08-20T03:39:41ZengAssociation of Basic Medical Sciences of Federation of Bosnia and HerzegovinaBiomolecules & Biomedicine2831-08962831-090X2025-08-0110.17305/bb.2025.12861Neuropeptide S pathway in PTSD and neuropsychiatric disorders: A reviewZhi-cheng Zhu0https://orcid.org/0009-0004-7036-7227Xue-jing Han1Zhen He2Meng-yang Liu3Ning Wu4Xiang-min Tong5 Fei Li6Beijing Institute of Pharmacology and Toxicology, Beijing, China; Department of Pharmacology, Hangzhou Normal University, Hangzhou, Zhejiang, China.Beijing Institute of Pharmacology and Toxicology, Beijing, China; Department of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.Beijing Institute of Pharmacology and Toxicology, Beijing, ChinaBeijing Institute of Pharmacology and Toxicology, Beijing, China; Department of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.Beijing Institute of Pharmacology and Toxicology, Beijing, ChinaDepartment of Hematology, Zhejiang Provincial People's Hospital and People's Hospital of Hangzhou Medical College, Hangzhou, ChinaBeijing Institute of Pharmacology and Toxicology, Beijing, China 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—acting through its G-protein-coupled NPS receptor (NPSR)—as a common regulator of these diverse phenotypes. This narrative review surveys studies published 2000–2024 in PubMed, Embase and Web of Science that examine NPS/NPSR involvement in core PTSD features and typical comorbidities. The 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)—changes 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. Translation remains limited by NPS’s rapid degradation, poor blood–brain-barrier penetration and scarcity of brain-penetrant NPSR ligands, but advances in intranasal delivery, lipid-acylated analogues, biased NPSR agonists and “humanised” NPSR-variant models offer promising solutions. Collectively, current pre-clinical and genetic evidence positions the NPS–NPSR 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. https://www.bjbms.org/ojs/index.php/bjbms/article/view/12861Post-traumatic stress disorderrelated neuropsychiatric disordersneuropeptide Sneuropeptide S receptorsingle nucleotide polymorphism |
| spellingShingle | Zhi-cheng Zhu Xue-jing Han Zhen He Meng-yang Liu Ning Wu Xiang-min Tong Fei Li Neuropeptide S pathway in PTSD and neuropsychiatric disorders: A review Biomolecules & Biomedicine Post-traumatic stress disorder related neuropsychiatric disorders neuropeptide S neuropeptide S receptor single nucleotide polymorphism |
| title | Neuropeptide S pathway in PTSD and neuropsychiatric disorders: A review |
| title_full | Neuropeptide S pathway in PTSD and neuropsychiatric disorders: A review |
| title_fullStr | Neuropeptide S pathway in PTSD and neuropsychiatric disorders: A review |
| title_full_unstemmed | Neuropeptide S pathway in PTSD and neuropsychiatric disorders: A review |
| title_short | Neuropeptide S pathway in PTSD and neuropsychiatric disorders: A review |
| title_sort | neuropeptide s pathway in ptsd and neuropsychiatric disorders a review |
| topic | Post-traumatic stress disorder related neuropsychiatric disorders neuropeptide S neuropeptide S receptor single nucleotide polymorphism |
| url | https://www.bjbms.org/ojs/index.php/bjbms/article/view/12861 |
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