title: Increased inflammatory markers identified in the dorsolateral prefrontal cortex of individuals with schizophrenia.
abstract: Upregulation of the immune response may be involved in the pathogenesis of schizophrenia with changes occurring in both peripheral blood and brain tissue. To date, microarray technology has provided a limited view of specific inflammatory transcripts in brain perhaps due to sensitivity issues. Here we used SOLiD Next Generation Sequencing to quantify neuroimmune mRNA expression levels in the dorsolateral prefrontal cortex of 20 individuals with schizophrenia and their matched controls. We detected 798 differentially regulated transcripts present in people with schizophrenia compared with controls. Ingenuity pathway analysis identified the inflammatory response as a key change. Using quantitative real-time PCR we confirmed the changes in candidate cytokines and immune modulators, including interleukin (IL)-6, IL-8, IL-1β and SERPINA3. The density of major histocompatibility complex-II-positive cells morphologically resembling microglia was significantly increased in schizophrenia and correlated with IL-1β expression. A group of individuals, most of whom had schizophrenia, were found to have increased inflammatory mRNA expression. In summary, we have demonstrated changes in an inflammatory response pathway that are present in ∼40% of people diagnosed with schizophrenia. This suggests that therapies aimed at immune system attenuation in schizophrenia may be of direct benefit in the brain.
authors.affiliation: Schizophrenia Research Institute, Sydney, New South Wales, Australia.
authors.forename: S G
authors.initials: SG
authors.lastname: Fillman
authors.forename: N
authors.initials: N
authors.lastname: Cloonan
authors.forename: V S
authors.initials: VS
authors.lastname: Catts
authors.forename: L C
authors.initials: LC
authors.lastname: Miller
authors.forename: J
authors.initials: J
authors.lastname: Wong
authors.forename: T
authors.initials: T
authors.lastname: McCrossin
authors.forename: M
authors.initials: M
authors.lastname: Cairns
authors.forename: C S
authors.initials: CS
authors.lastname: Weickert
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002874:Chromosome Mapping; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006682:HLA-DP Antigens / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D008297:Male; D017628:Microglia / Q000378:metabolism; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012559:Schizophrenia / Q000473:pathology*; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016207:Cytokines; D006682:HLA-DP Antigens; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; C516148:SERPINA3 protein, human; D015843:Serpins