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.

Convergent lines of evidence support CAMKK2 as a schizophrenia susceptibility gene

“…To seek the potential genes that are differentially expressed between schizophrenia patients and healthy controls, many expression microarrays have been performed and numerous dysregulated genes have been identified. [27][28][29][30] However, we noticed that only very limited overlapping genes were identified among different expression studies, which is likely due to the use of different brain regions and quantitative methods. In addition, the quality of the analyzed samples and sample size may also influence the identification of dysregulated genes in individuals with schizophrenia.…”

Gastroenterology issues in schizophrenia: Why the gut matters

“…In two different inflammatory diseases, one that occurs in the gut (IBD) and another that occurs in the CNS (multiple sclerosis, MS), there is a reorganization of tight junction proteins between epithelial cells of the respective gut (for IBD) and brain (for MS) barriers that results in a heightened permeability [76][77][78][79]. Inflammation, particularly of a low-grade nature, is a consistent pathological finding in schizophrenia [80][81][82], and as described earlier, some of this inflammation is associated with the GI tract [13]. Interestingly, T. gondii exposure is a well-documented risk factor for schizophrenia [83,84], and as a gut pathogen is a tool used in experimental models to produce an inflammatory state in the GI tract.…”

Increased levels of IL-6 in the cerebrospinal fluid of patients with chronic schizophrenia — significance for activation of the kynurenine pathway

“…5,6 Further, postmor tem studies using messenger RNA (mRNA) expression or im munohistochemical detection have shown increased levels of immune related compounds. [7][8][9] A number of investigations have focused on cytokines, but these studies have not yielded a unanimous picture, possibly because of a number of con founding factors, such as smoking and dietary habits, body mass index (BMI), type and duration of antipsychotic treat ment and drug abuse -all factors potentially affecting the immune system. 10 However, according to recent meta analyses, 11,12 some cytokines are significantly associated with schizophrenia (e.g., interleukin [IL] 6).…”