title: Innate immune response is differentially dysregulated between bipolar disease and schizophrenia.
abstract: Schizophrenia (SZ) and bipolar disorder (BD) are severe psychiatric conditions with a neurodevelopmental component. Genetic findings indicate the existence of an overlap in genetic susceptibility across the disorders. Also, image studies provide evidence for a shared neurobiological basis, contributing to a dimensional diagnostic approach. This study aimed to identify the molecular mechanisms that differentiate SZ and BD patients from health controls but also that distinguish both from health individuals. Comparison of gene expression profiling in post-mortem brains of both disorders and health controls (30 cases), followed by a further comparison between 29 BD and 29 SZ revealed 28 differentially expressed genes. These genes were used in co-expression analysesthat revealed the pairs CCR1/SERPINA1, CCR5/HCST, C1QA/CD68, CCR5/S100A11 and SERPINA1/TLR1 as presenting the most significant difference in co-expression between SZ and BD. Next, a protein-protein interaction (PPI) network using the 28 differentially expressed genes as seeds revealed CASP4, TYROBP, CCR1, SERPINA1, CCR5 and C1QA as having a central role in the diseases manifestation. Both co-expression and network topological analyses pointed to genes related to microglia functions. Based on this data, we suggest that differences between SZ and BP are due to genes involved with response to stimulus, defense response, immune system process and response to stress biological processes, all having a role in the communication of environmental factors to the cells and associated to microglia.
authors.affiliation: Institute of Psychiatry - University of Sao Paulo, Medical School (FMUSP), São Paulo (SP), Brazil.
authors.forename: Angelica
authors.initials: A
authors.lastname: de Baumont
authors.affiliation: Institute of Psychiatry - University of Sao Paulo, Medical School (FMUSP), São Paulo (SP), Brazil; Laboratory of Genomics and Molecular Biology/CIPE - AC Camargo Hospital Cancer Center, Sao Paulo (SP), Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: Maschietto
authors.affiliation: Laboratory of Genomics and Molecular Biology/CIPE - AC Camargo Hospital Cancer Center, Sao Paulo (SP), Brazil.
authors.forename: Leandro
authors.initials: L
authors.lastname: Lima
authors.affiliation: Laboratory of Genomics and Molecular Biology/CIPE - AC Camargo Hospital Cancer Center, Sao Paulo (SP), Brazil.
authors.forename: Dirce Maria
authors.initials: DM
authors.lastname: Carraro
authors.affiliation: Laboratory of Genomics and Molecular Biology/CIPE - AC Camargo Hospital Cancer Center, Sao Paulo (SP), Brazil.
authors.forename: Eloisa Helena
authors.initials: EH
authors.lastname: Olivieri
authors.affiliation: Laboratory of Genomics and Molecular Biology/CIPE - AC Camargo Hospital Cancer Center, Sao Paulo (SP), Brazil.
authors.forename: Alex
authors.initials: A
authors.lastname: Fiorini
authors.affiliation: Laboratory of Genomics and Molecular Biology/CIPE - AC Camargo Hospital Cancer Center, Sao Paulo (SP), Brazil.
authors.forename: Luiz André Nardin
authors.initials: LA
authors.lastname: Barreta
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Joana Almeida
authors.initials: JA
authors.lastname: Palha
authors.affiliation: Department of Psychiatry, Federal University of Rio Grande do Sul, PortoAlegre, Brazil.
authors.forename: Paulo
authors.initials: P
authors.lastname: Belmonte-de-Abreu
authors.affiliation: Department of Pediatrics, University of Sao Paulo, Medical School (FMUSP), Sao Paulo (SP), Brazil.
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Moreira Filho
authors.affiliation: Institute of Psychiatry - University of Sao Paulo, Medical School (FMUSP), São Paulo (SP), Brazil; LIM23 - University of Sao Paulo, Medical School (FMUSP), and Instituto Nacional de Psiquiatria para Infancia e Adolescencia, Sao Paulo (SP), Brazil. Electronic address: helena.brentani@gmail.com.
authors.forename: Helena
authors.initials: H
authors.lastname: Brentani
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001921:Brain / Q000378:metabolism; D053471:Caspases, Initiator / Q000235:genetics; D003172:Complement C1 / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D016014:Linear Models; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D054389:Receptors, CCR1 / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000515:alpha 1-Antitrypsin / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C515300:CCR1 protein, human; C584933:CCR5 protein, human; D003172:Complement C1; D008565:Membrane Proteins; D054389:Receptors, CCR1; D019713:Receptors, CCR5; C043392:SERPINA1 protein, human; C110546:TYROBP protein, human; D000515:alpha 1-Antitrypsin; C093516:CASP4 protein, human; D053471:Caspases, Initiator
keywords: bipolar disorder; co-expression; network; protein-protein interaction (PPI); schizophrenia