{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T09:00:23Z","timestamp":1776675623203,"version":"3.51.2"},"reference-count":234,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T00:00:00Z","timestamp":1776470400000},"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>Glucagon-like peptide-1 (GLP-1) and dual GIP\/GLP-1 receptor agonists, originally introduced for the management of type 2 diabetes mellitus and obesity, are increasingly recognized for their broader actions within the central nervous system, with emerging implications in neuropsychiatry and neurodegeneration. This review integrates current preclinical and clinical evidence, emphasizing their pharmacodynamic profile, central receptor distribution, and the molecular pathways linking metabolic signaling to neural function. Evidence suggests that GLP-1 receptor activation across key brain regions involved in energy balance and reward modulates multiple neurotransmitter systems, including dopamine and serotonin, as well as glutamatergic and GABAergic transmission, thereby influencing behavior, affective processes, and cognitive function. In parallel, these agents exhibit neuroprotective properties through improved neuronal insulin sensitivity, attenuation of neuroinflammatory pathways, and support of neuroplasticity, alongside effects on limiting pathological protein aggregation. Dual GIP\/GLP-1 agonism may further potentiate these central actions through complementary metabolic and synaptic mechanisms. Although pharmacovigilance data have identified isolated neuropsychiatric adverse events, current clinical evidence does not support a consistent causal association. Collectively, incretin-based therapies represent a promising translational approach at the interface of metabolic and neuropsychiatric disorders, warranting further investigation into their long-term central safety, therapeutic efficacy, and clinical relevance.<\/jats:p>","DOI":"10.3390\/ijms27083628","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T08:24:23Z","timestamp":1776673463000},"page":"3628","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Glucagon-like Peptide-1 and Dual GIP\/GLP-1 Receptor Agonists in Brain: Exploring the Expanding Role and Safety in Neuropsychiatry"],"prefix":"10.3390","volume":"27","author":[{"given":"Ana Cristina","family":"Tudosie","sequence":"first","affiliation":[{"name":"Department of Endocrinology, University of Medicine and Pharmacy, 200349 Craiova, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loredana-Maria","family":"Marin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Physics, Faculty of Pharmacy, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020956 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona Georgiana","family":"Popa","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Nutrition and Metabolic Diseases, University of Medicine and Pharmacy, 200349 Craiova, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1802-3601","authenticated-orcid":false,"given":"Andreea Loredana","family":"Golli","sequence":"additional","affiliation":[{"name":"Department of Public Health and Healthcare Management, University of Medicine and Pharmacy, 200349 Craiova, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Liu, Q.K. 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