{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T16:10:52Z","timestamp":1779207052908,"version":"3.51.4"},"reference-count":165,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"METIS ONLUS"},{"name":"Consulta Delta Erre Trust Company S.R.L."},{"name":"Ministry of University and Research (MUR), the National Recovery and Resilience Plan"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Severe mental disorders, including schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD), are leading causes of global disability, yet current treatments remain largely symptomatic and fail to alter disease trajectories. Converging evidence from genetics, longitudinal studies, and systems neuroscience supports a dimensional and transdiagnostic architecture of psychopathology, involving shared polygenic risk and overlapping neurodevelopmental and circuit-level alterations. Traditional approaches\u2014such as post-mortem brain analysis, neuroimaging, and animal models\u2014have delineated core molecular perturbations (e.g., dopaminergic, glutamatergic, and GABAergic dysfunction), as well as informed translational frameworks for mechanistic investigation, but remain constrained by restricted access to dynamic processes and incomplete recapitulation of human-specific biology. The advent of human-derived cellular models, particularly human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), has partially addressed these limitations, enabling the study of patient-specific neurodevelopment and synaptic function in vitro. Within this evolving landscape, the olfactory neuroepithelium (ONE) has emerged as an accessible source of neural progenitors, obtainable through minimally invasive procedures, providing a window into living human neurobiology. ONE-derived cells retain donor-specific genetic and epigenetic signatures while recapitulating disease-relevant phenotypes across major psychiatric disorders, including altered neurodevelopmental dynamics, synaptic gene expression, and inflammatory profiles. Here, we present a narrative review of the principal cellular and tissue models used in biological psychiatry, examining their respective strengths, limitations, and translational relevance across experimental contexts. By situating these approaches within a unified framework, we aim to clarify their complementarity, identify current gaps, and outline future directions, highlighting the emerging potential of ONE-based models to bridge genetic risk, cellular dysfunction, and clinical phenotype, thereby advancing precision psychiatry.<\/jats:p>","DOI":"10.3390\/brainsci16050523","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T15:17:23Z","timestamp":1779203843000},"page":"523","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Human-Derived Cellular Models in Psychiatry: A Focus on the Olfactory Neuroepithelium"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5510-5761","authenticated-orcid":false,"given":"Tommaso","family":"Toffanin","sequence":"first","affiliation":[{"name":"Department of Neuroscience and Rehabilitation, Institute of Psychiatry, University of Ferrara, Via Fossato di Mortara, 64\/A, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4186-7658","authenticated-orcid":false,"given":"Mario Angelo","family":"Pagano","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Rehabilitation, Institute of Psychiatry, University of Ferrara, Via Fossato di Mortara, 64\/A, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Idotta","sequence":"additional","affiliation":[{"name":"Metis ETS, 35018 San Martino di Lupari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1050-4494","authenticated-orcid":false,"given":"Luigi","family":"Grassi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Rehabilitation, Institute of Psychiatry, University of Ferrara, Via Fossato di Mortara, 64\/A, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3481-9503","authenticated-orcid":false,"given":"Anna Maria","family":"Brunati","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Padova, 35121 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"ref_1","unstructured":"WHO (2023). 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