Lilah Toker1, Burak Ogan Mancarci2, Shreejoy Tripathy1, Paul Pavlidis3. 1. Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada. 2. Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada; Graduate Program in Bioinformatics, University of British Columbia, Vancouver, British Columbia, Canada. 3. Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: paul@msl.ubc.ca.
Abstract
BACKGROUND: High-throughput expression analyses of postmortem brain tissue have been widely used to study bipolar disorder and schizophrenia. However, despite the extensive efforts, no consensus has emerged as to the functional interpretation of the findings. We hypothesized that incorporating information on cell type-specific expression would provide new insights. METHODS: We reanalyzed 15 publicly available bulk tissue expression datasets on schizophrenia and bipolar disorder, representing various brain regions from eight different cohorts of subjects (unique subjects: 332 control, 129 bipolar disorder, 341 schizophrenia). We studied changes in the expression profiles of cell type marker genes and evaluated whether these expression profiles could serve as surrogates for relative abundance of their corresponding cells. RESULTS: In both bipolar disorder and schizophrenia, we consistently observed an increase in the expression profiles of cortical astrocytes and a decrease in the expression profiles of fast-spiking parvalbumin interneurons. No changes in astrocyte expression profiles were observed in subcortical regions. Furthermore, we found that many of the genes previously identified as differentially expressed in schizophrenia are highly correlated with the expression profiles of astrocytes or fast-spiking parvalbumin interneurons. CONCLUSIONS: Our results indicate convergence of transcriptome studies of schizophrenia and bipolar disorder on changes in cortical astrocytes and fast-spiking parvalbumin interneurons, providing a unified interpretation of numerous studies. We suggest that these changes can be attributed to alterations in the relative abundance of the cells and are important for understanding the pathophysiology of the disorders.
BACKGROUND: High-throughput expression analyses of postmortem brain tissue have been widely used to study bipolar disorder and schizophrenia. However, despite the extensive efforts, no consensus has emerged as to the functional interpretation of the findings. We hypothesized that incorporating information on cell type-specific expression would provide new insights. METHODS: We reanalyzed 15 publicly available bulk tissue expression datasets on schizophrenia and bipolar disorder, representing various brain regions from eight different cohorts of subjects (unique subjects: 332 control, 129 bipolar disorder, 341 schizophrenia). We studied changes in the expression profiles of cell type marker genes and evaluated whether these expression profiles could serve as surrogates for relative abundance of their corresponding cells. RESULTS: In both bipolar disorder and schizophrenia, we consistently observed an increase in the expression profiles of cortical astrocytes and a decrease in the expression profiles of fast-spiking parvalbumin interneurons. No changes in astrocyte expression profiles were observed in subcortical regions. Furthermore, we found that many of the genes previously identified as differentially expressed in schizophrenia are highly correlated with the expression profiles of astrocytes or fast-spiking parvalbumin interneurons. CONCLUSIONS: Our results indicate convergence of transcriptome studies of schizophrenia and bipolar disorder on changes in cortical astrocytes and fast-spiking parvalbumin interneurons, providing a unified interpretation of numerous studies. We suggest that these changes can be attributed to alterations in the relative abundance of the cells and are important for understanding the pathophysiology of the disorders.
Authors: Andrea Hasenstaub; Stephani Otte; Edward Callaway; Terrence J Sejnowski Journal: Proc Natl Acad Sci U S A Date: 2010-06-23 Impact factor: 11.205
Authors: Christine Konradi; Eric I Zimmerman; C Kevin Yang; Kathryn M Lohmann; Paul Gresch; Harry Pantazopoulos; Sabina Berretta; Stephan Heckers Journal: Arch Gen Psychiatry Date: 2010-12-06
Authors: Giselli Scaini; Gislaine T Rezin; Andre F Carvalho; Emilio L Streck; Michael Berk; João Quevedo Journal: Neurosci Biobehav Rev Date: 2016-07-01 Impact factor: 8.989
Authors: Spyros Darmanis; Steven A Sloan; Ye Zhang; Martin Enge; Christine Caneda; Lawrence M Shuer; Melanie G Hayden Gephart; Ben A Barres; Stephen R Quake Journal: Proc Natl Acad Sci U S A Date: 2015-05-18 Impact factor: 11.205
Authors: Yunting Zhu; Maree J Webster; Caitlin E Murphy; Frank A Middleton; Paul T Massa; Chunyu Liu; Rujia Dai; Cyndi Shannon Weickert Journal: Front Neurosci Date: 2022-06-30 Impact factor: 5.152
Authors: Leanna M Hernandez; Minsoo Kim; Gil D Hoftman; Jillian R Haney; Luis de la Torre-Ubieta; Bogdan Pasaniuc; Michael J Gandal Journal: Biol Psychiatry Date: 2020-06-12 Impact factor: 13.382