Concordance of inflammatory markers in lymphocytes and prefrontal cortex in schizophrenia. 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 0.5) 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. Overall design: Investigation of gene expression profiles in lymphocytes from 18 non-psychotic controls and 19 individuals with schizophrenia.