Concordance of inflammatory markers in lymphocytes and prefrontal cortex in schizophrenia

Schizophrenia is a severe neuropsychiatric disorder associated with a wide array of transcriptomic and neurobiochemical changes. Genome-wide transcriptomic profiling conducted in postmortem brain have provided novel insights into the pathophysiology of this disorder, and identified biological processes including immune/inflammatory-related responses, metabolic, endocrine and synaptic function. However, few studies have investigated whether similar changes could be found in peripheral tissue. Here, we used RNA-sequencing to characterize transcriptomic profiles of lymphocytes in 18 non-psychotic controls and 19 individuals with schizophrenia. We identified 2,819 differentially expressed transcripts (pnominal < 0.05) in the schizophrenia group when compared to controls. Bioinformatic analyses conducted on a subset of 293 genes (pnominal < 0.01 and |log2FC| > 0.5) highlighted immune/inflammatory response as key biological processes in our dataset. Differentially expressed genes in lymphocytes were highly enriched for gene expression profiles from cortex layer 5a & immune cells. Thus, we investigated whether the changes in transcripts levels we observed in lymphocytes could also be detected in the prefrontal cortex (PFC, BA10) in a second validation cohort of schizophrenia subjects. Remarkably, mRNA levels detected in the PFC and lymphocytes were in strong agreement, and measurements obtained using RNA-sequencing were positively correlated with data obtained by RT-qPCR analysis. Collectively, our work supports a role for immune dysfunction in the pathogenesis of schizophrenia and suggest that peripheral markers can be used as accessible surrogates to investigate putative central nervous system disruptions. Investigation of gene expression profiles in lymphocytes from 18 non-psychotic controls and 19 individuals with schizophrenia.