{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T10:49:45Z","timestamp":1789296585021,"version":"build-2803163510"},"reference-count":67,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T00:00:00Z","timestamp":1762646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Zinc (Zn2+) is a trace element essential for its catalytic, antioxidant, and immunomodulatory roles extending to synaptic signalling in the central nervous system. In this narrative review, we aim to offer the reader evidence linking perturbations of the Zn2+ homeostasis, including deficiency, excess, or transportation anomalies, to neuropsychiatric conditions such as Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BD). A targeted, unsystematic PubMed search followed by an extensive pearl-growing strategy was applied to further augment study selection based on the extensive expertise of study authors. Overall, most of the evidence currently available suggests a modest benefit for a Zn2+ supplement of around 25\u201330 mg\/day as an augmentation to MDD treatment, with potential benefits of smaller magnitude in paediatric ADHD. Evidence for perturbations of Zn2+ as a biomarker of risk for these neuropsychiatric disorders remains unconvincing. The role of Zn2+ supplements in the treatment of the selected conditions remains largely unknown due to the lack of specific, randomised controlled trials conducted to explore their efficacy. The long-term safety, optimal doses for specific applications, and the exploration of possible biomarkers to stratify patient selection to identify the optimal candidate for Zn2+ supplements remain unanswered questions.<\/jats:p>","DOI":"10.3390\/ijms262210877","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T08:57:55Z","timestamp":1762765075000},"page":"10877","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Perturbations of Zinc Homeostasis and Onset of Neuropsychiatric Disorders"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0189-8612","authenticated-orcid":false,"given":"Gavino","family":"Faa","sequence":"first","affiliation":[{"name":"Department of Medical Sciences and Public Health, University of Cagliari, 09042 Cagliari, Italy"},{"name":"Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlotta","family":"Meloni","sequence":"additional","affiliation":[{"name":"Section of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Lastretti","sequence":"additional","affiliation":[{"name":"Department of Economic, Psychological and Communication Sciences, Niccol\u00f2 Cusano University, 00166 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Pinna","sequence":"additional","affiliation":[{"name":"Forensic Psychiatry Unit, Department of Mental Health and Addiction, Health Agency of Cagliari, 09124 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4175-6413","authenticated-orcid":false,"given":"Mirko","family":"Manchia","sequence":"additional","affiliation":[{"name":"Section of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy"},{"name":"Department of Pharmacology, Dalhousie University, Halifax, NS B3K 6R8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9953-6929","authenticated-orcid":false,"given":"Pasquale","family":"Paribello","sequence":"additional","affiliation":[{"name":"Section of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,9]]},"reference":[{"key":"ref_1","first-page":"809","article-title":"Multifunctional Role of Zinc in Human Health: An Update","volume":"22","author":"Kiouri","year":"2023","journal-title":"EXCLI J."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Moretti, A.I.S., Baksheeva, V.E., Roman, A.Y., De Bessa, T.C., Devred, F., Kovacic, H., and Tsvetkov, P.O. 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