Preliminary evidence of ubiquitin proteasome system dysregulation in schizophrenia and bipolar disorder: Convergent pathway analysis findings from two independent samples
| Autor: | Sharon D. Chandler, James B. Lohr, William S. Kremen, Ian P. Everall, Ginger R. Lucero, Stephen J. Glatt, Todd May, Chad A. Bousman, Gursharan Chana, Erick T. Tatro, Ming T. Tsuang |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Oncology Proteasome Endopeptidase Complex medicine.medical_specialty Psychosis Bipolar Disorder Microarray Taiwan Article Cellular and Molecular Neuroscience Ubiquitin Internal medicine mental disorders medicine Humans RNA Messenger Bipolar disorder Genetics (clinical) Oligonucleotide Array Sequence Analysis Genetics Regulation of gene expression Models Genetic biology business.industry Case-control study Middle Aged medicine.disease Psychiatry and Mental health Gene Expression Regulation Psychotic Disorders Proteasome Schizophrenia Case-Control Studies biology.protein Female business Software |
| Zdroj: | American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. :494-502 |
| ISSN: | 1552-4841 |
| DOI: | 10.1002/ajmg.b.31006 |
| Popis: | Schizophrenia (SCZ) and bipolar disorder (BPD) are polygenic disorders with many genes contributing to their etiologies. The aim of this investigation was to search for dysregulated molecular and cellular pathways for these disorders as well as psychosis. We conducted a blood-based microarray investigation in two independent samples with SCZ and BPD from San Diego (SCZ = 13, BPD = 9, control = 8) and Taiwan (SCZ = 11, BPD = 14, control = 16). Diagnostic groups were compared to controls, and subjects with a history of psychosis [PSYCH(+): San Diego (n = 6), Taiwan (n = 14)] were compared to subjects without such history [PSYCH(-): San Diego (n = 11), Taiwan (n = 14)]. Analyses of covariance comparing mean expression levels on a gene-by-gene basis were conducted to generate the top 100 significantly dysregulated gene lists for both samples by each diagnostic group. Gene lists were imported into Ingenuity Pathway Analysis (IPA) software. Results showed the ubiquitin proteasome pathway (UPS) was listed in the top ten canonical pathways for BPD and psychosis diagnostic groups across both samples with a considerably low likelihood of a chance occurrence (P = 0.001). No overlap in dysregulated genes populating these pathways was observed between the two independent samples. Findings provide preliminary evidence of UPS dysregulation in BPD and psychosis as well as support further investigation of the UPS and other molecular and cellular pathways for potential biomarkers for SCZ, BPD, and/or psychosis. |
| Databáze: | OpenAIRE |
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