Cell-type specific reductions in interneuron gene expression within the cingulate gyrus of schizophrenia and bipolar disorder subjects
Abstract Schizophrenia (SZ) and bipolar disorder (BP) patients share overlapping neurocognitive deficits of varied magnitude. Neuroimaging in patients and postmortem gene expression analyses suggest that compromised cingulate gyrus GABA-ergic interneurons may contribute to cognitive impairments in S...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-06-01
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| Series: | Schizophrenia |
| Online Access: | https://doi.org/10.1038/s41537-025-00638-6 |
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| author | David M. Krolewski Huzefa Khalil Maria Waselus Marquis P. Vawter Blynn G. Bunney Richard M. Myers Francis S. Y. Lee Alan F. Schatzberg William E. Bunney Huda Akil Stanley J. Watson |
| author_facet | David M. Krolewski Huzefa Khalil Maria Waselus Marquis P. Vawter Blynn G. Bunney Richard M. Myers Francis S. Y. Lee Alan F. Schatzberg William E. Bunney Huda Akil Stanley J. Watson |
| author_sort | David M. Krolewski |
| collection | DOAJ |
| description | Abstract Schizophrenia (SZ) and bipolar disorder (BP) patients share overlapping neurocognitive deficits of varied magnitude. Neuroimaging in patients and postmortem gene expression analyses suggest that compromised cingulate gyrus GABA-ergic interneurons may contribute to cognitive impairments in SZ and BP. To address this, we used radioactive in situ hybridization to investigate potential gene expression signatures for SZ and BP using interneuron cell-type specific markers including glutamic acid decarboxylase (GAD67), parvalbumin (PV), somatostatin (SST), and vasoactive intestinal peptide (VIP) within specific Brodmann’s areas (BA) of the cingulate gyrus. We report reduced GAD67 mRNA in anterior midcingulate cortex (aMCC) of BP subjects within BA24c’, the most dysregulated subregion across disorders that also demonstrated reduced PV and VIP mRNA in the SZ group. In the retrosplenial (RSC) and ectosplenial (ESC) cortices, decreases in PV expression were shared by both SZ and BP subjects. Our results show unique and shared transcription signatures of two disorders in specific cingulate gyrus regions and cell types. SZ and BP displayed divergent aMCC gene expression reductions suggesting transcriptional changes are associated with disease-specific gene/subregion signatures, potentially underlying differential subregional dysregulation within areas associated with error detection/action monitoring and the salience network. In RSC/ESC, transcriptional changes are associated with more common expression patterns, possibly related to overlapping effects on visuospatial memory processing and allocation of attentional resources involving the default mode network. |
| format | Article |
| id | doaj-art-eeadcc57ff274198891febe061f759c9 |
| institution | Kabale University |
| issn | 2754-6993 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Schizophrenia |
| spelling | doaj-art-eeadcc57ff274198891febe061f759c92025-08-20T03:47:14ZengNature PortfolioSchizophrenia2754-69932025-06-0111111010.1038/s41537-025-00638-6Cell-type specific reductions in interneuron gene expression within the cingulate gyrus of schizophrenia and bipolar disorder subjectsDavid M. Krolewski0Huzefa Khalil1Maria Waselus2Marquis P. Vawter3Blynn G. Bunney4Richard M. Myers5Francis S. Y. Lee6Alan F. Schatzberg7William E. Bunney8Huda Akil9Stanley J. Watson10Michigan Neuroscience Institute, University of MichiganMichigan Neuroscience Institute, University of MichiganMichigan Neuroscience Institute, University of MichiganUniversity of California-IrvineUniversity of California-IrvineHudsonAlpha Institute for BiotechnologyCornell UniversityStanford UniversityUniversity of California-IrvineMichigan Neuroscience Institute, University of MichiganMichigan Neuroscience Institute, University of MichiganAbstract Schizophrenia (SZ) and bipolar disorder (BP) patients share overlapping neurocognitive deficits of varied magnitude. Neuroimaging in patients and postmortem gene expression analyses suggest that compromised cingulate gyrus GABA-ergic interneurons may contribute to cognitive impairments in SZ and BP. To address this, we used radioactive in situ hybridization to investigate potential gene expression signatures for SZ and BP using interneuron cell-type specific markers including glutamic acid decarboxylase (GAD67), parvalbumin (PV), somatostatin (SST), and vasoactive intestinal peptide (VIP) within specific Brodmann’s areas (BA) of the cingulate gyrus. We report reduced GAD67 mRNA in anterior midcingulate cortex (aMCC) of BP subjects within BA24c’, the most dysregulated subregion across disorders that also demonstrated reduced PV and VIP mRNA in the SZ group. In the retrosplenial (RSC) and ectosplenial (ESC) cortices, decreases in PV expression were shared by both SZ and BP subjects. Our results show unique and shared transcription signatures of two disorders in specific cingulate gyrus regions and cell types. SZ and BP displayed divergent aMCC gene expression reductions suggesting transcriptional changes are associated with disease-specific gene/subregion signatures, potentially underlying differential subregional dysregulation within areas associated with error detection/action monitoring and the salience network. In RSC/ESC, transcriptional changes are associated with more common expression patterns, possibly related to overlapping effects on visuospatial memory processing and allocation of attentional resources involving the default mode network.https://doi.org/10.1038/s41537-025-00638-6 |
| spellingShingle | David M. Krolewski Huzefa Khalil Maria Waselus Marquis P. Vawter Blynn G. Bunney Richard M. Myers Francis S. Y. Lee Alan F. Schatzberg William E. Bunney Huda Akil Stanley J. Watson Cell-type specific reductions in interneuron gene expression within the cingulate gyrus of schizophrenia and bipolar disorder subjects Schizophrenia |
| title | Cell-type specific reductions in interneuron gene expression within the cingulate gyrus of schizophrenia and bipolar disorder subjects |
| title_full | Cell-type specific reductions in interneuron gene expression within the cingulate gyrus of schizophrenia and bipolar disorder subjects |
| title_fullStr | Cell-type specific reductions in interneuron gene expression within the cingulate gyrus of schizophrenia and bipolar disorder subjects |
| title_full_unstemmed | Cell-type specific reductions in interneuron gene expression within the cingulate gyrus of schizophrenia and bipolar disorder subjects |
| title_short | Cell-type specific reductions in interneuron gene expression within the cingulate gyrus of schizophrenia and bipolar disorder subjects |
| title_sort | cell type specific reductions in interneuron gene expression within the cingulate gyrus of schizophrenia and bipolar disorder subjects |
| url | https://doi.org/10.1038/s41537-025-00638-6 |
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