Schizophrenia is a genetically complex neuropsychiatric disorder with largely unresolved mechanisms of pathology. Identification of genes and pathways associated with
schizophrenia is important for understanding the development, progression and treatment of
schizophrenia. In this study, pathways associated with
schizophrenia were explored at the level of gene expression. The study included post-mortem brain tissue samples from 68
schizophrenia patients and 44 age and sex-matched control subjects. Whole transcriptome
poly-A selected paired-end
RNA sequencing was performed on tissue from the prefrontal cortex and orbitofrontal cortex.
RNA expression differences were detected between case and control individuals, focusing both on single genes and pathways. The results were validated with RT-qPCR. Significant differential expression between patient and controls groups was found for 71 genes. Gene ontology analysis of differentially expressed genes revealed an up-regulation of multiple genes in immune response among the patients (corrected p-value = 0.004). Several genes in the category belong to the
complement system, including C1R, C1S, C7, FCN3,
SERPING1, C4A and
CFI. The increased
complement expression is primarily driven by a subgroup of patients with increased expression of immune/inflammatory response genes, pointing to important differences in disease etiology within the patient group. Weighted gene co-expression network analysis highlighted networks associated with both synaptic transmission and activation of the immune response. Our results demonstrate the importance of immune-related pathways in
schizophrenia and provide evidence for elevated expression of the
complement cascade as an important pathway in
schizophrenia pathology.