Postmortem transcriptional profiling reveals widespread increase in inflammation in schizophrenia: a comparison of prefrontal cortex, striatum, and hippocampus among matched tetrads of controls with subjects diagnosed with schizophrenia, bipolar or major depressive disorder
| Autor: | Dmitri Volfson, Robin J. Kleiman, David A. Lewis, Larry C. James, Veronica Reinhart, Stacey J. Sukoff Rizzo, Thomas A. Lanz, Mark J. Sheehan, Susan E. Bove |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Bipolar Disorder medicine.medical_treatment Prefrontal Cortex Striatum Hippocampal formation Molecular neuroscience Hippocampus Article lcsh:RC321-571 Rats Sprague-Dawley 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Internal medicine Medicine Animals Humans Bipolar disorder Prefrontal cortex Antipsychotic lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Biological Psychiatry Inflammation Depressive Disorder Major business.industry Gene Expression Profiling medicine.disease Corpus Striatum 3. Good health Rats Gene expression profiling Dorsolateral prefrontal cortex Psychiatry and Mental health 030104 developmental biology Endocrinology medicine.anatomical_structure Schizophrenia Major depressive disorder Autopsy business 030217 neurology & neurosurgery |
| Zdroj: | Translational Psychiatry, Vol 9, Iss 1, Pp 1-13 (2019) Translational Psychiatry |
| ISSN: | 2158-3188 |
| Popis: | Psychiatric disorders such as schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD) arise from complex interactions between genetic and environmental factors. Common genetic variants associated with multiple psychiatric disorders suggest that shared genetic architecture could contribute to divergent clinical syndromes. To evaluate shared transcriptional alterations across connected brain regions, Affymetrix microarrays were used to profile postmortem dorsolateral prefrontal cortex (DLPFC), hippocampus, and associative striatum from 19 well-matched tetrads of subjects with SCZ, BD, MDD, or unaffected controls. SCZ subjects showed a substantial burden of differentially expressed genes across all examined brain regions with the greatest effects in hippocampus, whereas BD and MDD showed less robust alterations. Pathway analysis of transcriptional profiles compared across diagnoses demonstrated commonly enriched pathways between all three disorders in hippocampus, significant overlap between SCZ and BD in DLPFC, but no significant overlap of enriched pathways between disorders in striatum. SCZ samples showed increased expression of transcripts associated with inflammation across all brain regions examined, which was not evident in BD or MDD, or in rat brain following chronic dosing with antipsychotic drugs. Several markers of inflammation were confirmed by RT-PCR in hippocampus, including S100A8/9, IL-6, MAFF, APOLD1, IFITM3, and BAG3. A cytokine ELISA panel showed significant increases in IL-2 and IL-12p70 protein content in hippocampal tissue collected from same SCZ subjects when compared to matched control subjects. These data suggest an overlapping subset of dysregulated pathways across psychiatric disorders; however, a widespread increase in inflammation appears to be a specific feature of the SCZ brain and is not likely to be attributable to chronic antipsychotic drug treatment. |
| Databáze: | OpenAIRE |
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