{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T02:42:48Z","timestamp":1789526568685,"version":"build-2803163510"},"reference-count":138,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Background: Cognitive and psychiatric disorders are caused by a complex interplay between genetic predisposition, environmental exposures, and dynamic molecular regulation in the brain. Animal models provide a controlled environment for examining these mechanisms, and advances in transcriptome and epigenomic technologies have greatly expanded our knowledge of disease-relevant pathways. Objective: This scoping review systematically maps and synthesizes the epigenetic and transcriptomic findings from the established animal models of four neuropsychiatric conditions\u2014autism spectrum disorder (ASD), schizophrenia, depression, and Rett syndrome\u2014drawing on a PRISMA-ScR-guided literature search. The review characterizes the breadth of evidence, identifies convergent and divergent molecular pathways, and highlights the translational gaps and therapeutic implications. Methods: Research employing chromatin accessibility testing, genome-wide DNA methylation mapping, single-cell and bulk RNA sequencing, histone modification profiling, and multi-omics integration in mouse and other validated animal models was thoroughly reviewed. A quality appraisal of the primary experimental studies (n = 63) was performed using a modified CAMARADES checklist. Results: Beyond generalized cellular stress responses, multi-omics analysis emphasizes the cell-type- and context-dependent nature of epigenetic changes in animal models, including isoform-specific histone modifications and model-dependent binding of HDAC\/MeCP2 complexes to genes involved in synaptic plasticity. Single-cell RNA sequencing analyses have uniformly shown transcriptional changes in parvalbumin-positive (PV+) interneurons. Conclusions: The specific convergence of epigenetic disruptions in neural circuits involved in synaptic structure and inhibitory function could play a role in the generation of neuropsychiatric phenotypes in animal models, highlighting the importance of circuit- and cell-type-specific epigenetics while pointing to potential therapeutic avenues.<\/jats:p>","DOI":"10.3390\/cimb48040425","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T07:57:21Z","timestamp":1776758241000},"page":"425","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Epigenetic and Transcriptomic Pathways Underlying Animal Models of Cognitive and Psychiatric Disorders: A Scoping Review"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6075-7505","authenticated-orcid":false,"given":"Jaishriram","family":"Rathored","sequence":"first","affiliation":[{"name":"Department of Central Research Laboratory and Molecular Diagnostics, Datta Meghe Institute of Higher Education & Research, Sawangi Meghe, Wardha 442001, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4615-9282","authenticated-orcid":false,"given":"Ajay","family":"Pal","sequence":"additional","affiliation":[{"name":"Centre for Neural Development and Repair (CNDR), Lewis Katz School of Medicine, Temple University, 3500 N. Broad St., Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepika","family":"Sai Painkra","sequence":"additional","affiliation":[{"name":"Department of Central Research Laboratory and Molecular Diagnostics, Datta Meghe Institute of Higher Education & Research, Sawangi Meghe, Wardha 442001, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/nature09552","article-title":"Rethinking schizophrenia","volume":"468","author":"Insel","year":"2010","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15067","DOI":"10.1038\/nrdp.2015.67","article-title":"Schizophrenia","volume":"1","author":"Kahn","year":"2015","journal-title":"Nat. Rev. Dis. 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