Systems-Level Transcriptomic and Cellular Architecture of the Human Striatum in Schizophrenia and Bipolar Psychosis.
4 affiliations
- 1Department of Anesthesiology, Tri-Service General Hospital, National Defense Medical University, Taipei City 114202, Taiwan.
- 2Department of Anesthesiology, School of Medicine, College of Medicine, National Defense Medical University, Taipei City 114201, Taiwan.
- 3Graduate Institute of Biochemistry, College of Biomedical Sciences, National Defense Medical University, Taipei City 114201, Taiwan.
- 4Department of Pharmacy, Chi-Mei Medical Center, Tainan City 710402, Taiwan.
Abstract
Psychosis involves striatal circuit dysfunction, but the regional molecular and cellular changes remain unclear. 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 < 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-inflammatory 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-adenosine, glutamate-calcium, Activin-SMAD, 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-striatal, schizophrenia-associated transcriptional and oligodendroglial signal and provide prioritized hypotheses for independent validation.
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BibTeX
@article{chan2026systemslevel,
title = {{Systems-Level Transcriptomic and Cellular Architecture of the Human Striatum in Schizophrenia and Bipolar Psychosis.}},
author = {Wei-Hung Chan and Shih-Ming Huang and Hui-Chen Su and Yi-Lin Chiu},
journal = {Biology},
year = {2026},
month = sep,
doi = {10.3390/biology15191714},
url = {https://europepmc.org/article/MED/42883387},
note = {CC BY},
}
RIS
TY - JOUR
TI - Systems-Level Transcriptomic and Cellular Architecture of the Human Striatum in Schizophrenia and Bipolar Psychosis.
AU - Wei-Hung Chan
AU - Shih-Ming Huang
AU - Hui-Chen Su
AU - Yi-Lin Chiu
PY - 2026
DA - 2026/09/26
JO - Biology
DO - 10.3390/biology15191714
UR - https://europepmc.org/article/MED/42883387
AB - Psychosis involves striatal circuit dysfunction, but the regional molecular and cellular changes remain unclear. 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 < 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-inflammatory 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-adenosine, glutamate-calcium, Activin-SMAD, 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-striatal, schizophrenia-associated transcriptional and oligodendroglial signal and provide prioritized hypotheses for independent validation.
SN - 2079-7737
ER -