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We re-analyzed 215 postmortem RNA-seq samples (72 donors: 36 controls, 28 schizophrenia, 8 bipolar disorder with psychosis) from the nucleus accumbens, caudate and putamen, asking whether diagnosis-associated transcriptional changes are region-specific and whether they reflect cellular composition or cell-intrinsic state. Region-specific limma-voom models identified 0, 141 and 2152 schizophrenia-associated genes (FDR &lt; 0.10) in the nucleus accumbens, caudate and putamen; the small bipolar-psychosis group yielded one gene, with limited power to detect additional associations. Correlation-aware camera tests supported immune\u2013inflammatory Hallmark programs in the caudate and putamen, whereas nucleus accumbens signals were not robust to sequencing-run adjustment. Leukocyte-reference deconvolution was uninformative for brain parenchyma. Across four deconvolution estimators and two single-nucleus references, including an independent eight-donor striatal reference, putamen samples from donors with schizophrenia showed a consistently lower oligodendrocyte-lineage reference weight, whereas attribution to oligodendrocyte precursor cells specifically was method-dependent. Exploratory directional signatures (dopamine\u2013adenosine, glutamate\u2013calcium, Activin\u2013SMAD, APP processing) remained supported in the caudate and putamen after direction-selection permutation conditional on fixed gene membership and were driven mainly by schizophrenia. The results characterize a dorsal\u2013striatal, schizophrenia-associated transcriptional and oligodendroglial signal and provide prioritized hypotheses for independent validation.<\/jats:p>","DOI":"10.3390\/biology15191714","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T08:18:46Z","timestamp":1790583526000},"page":"1714","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Systems-Level Transcriptomic and Cellular Architecture of the Human Striatum in Schizophrenia and Bipolar Psychosis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5514-8932","authenticated-orcid":false,"given":"Wei-Hung","family":"Chan","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Tri-Service General Hospital, National Defense Medical University, Taipei City 114202, Taiwan"},{"name":"Department of Anesthesiology, School of Medicine, College of Medicine, National Defense Medical University, Taipei City 114201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Shih-Ming","family":"Huang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biochemistry, College of Biomedical Sciences, National Defense Medical University, Taipei City 114201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Hui-Chen","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Chi-Mei Medical Center, Tainan City 710402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1827-6924","authenticated-orcid":false,"given":"Yi-Lin","family":"Chiu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biochemistry, College of Biomedical Sciences, National Defense Medical University, Taipei City 114201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1002\/wps.20310","article-title":"Psychosis as a transdiagnostic and extended phenotype in the general population","volume":"15","author":"Reininghaus","year":"2016","journal-title":"World 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