background Schizophrenia is to a large extent genetically determined, but, until now, the functioning of the genome has not been studied. Previously, we analyzed whole-genome gene expression profiles of Peripheral Blood Mononuclear Cells (pbmcs), comparing schizophrenia patients vs controls. Based on pilot data study we hypothesized that akt1 expression is decreased in pbmcs of schizophrenia patients as compared to controls.
aim To test whether epistasis at the transcriptional level in response to lower akt1 expression in patients will lead to deregulation of functional biological processes in which akt1 plays an important role.
methods We performed a case-control study, investigating male, recent onset (<5 years) schizophrenia patients (N=41) as compared to controls (N=29). pbmc gene expression was measured using the Affymetrix Human Genome U133 plus 2.0 GeneChip® microarray.
results We found decreased expression of akt1 in patients vs controls (p<0.001, t= -4.25). Furthermore a total of 1224 genes were differentially expressed between patients and controls (fdr=0.05). Biological processes associated with the deregulated gene set were associated with immune processes, cell adhesion and neuronal guidance, neurotrophins and (neural) growth factors, oxidative stress and glucose metabolism, and apoptosis and cell-cycle regulation.
conclusion In conclusion, decreased pbmc akt1 expression may be a trait factor for schizophrenia in male patients. A majority of the processes found deregulated between patients and controls play a prominent role in current hypotheses on the origins of schizophrenia. (Cultured) pbmcs may be a useful tissue in which to investigate aspects of the molecular biology of schizophrenia. We also conclude that in schizophrenia, whole-genome gene expression studies of a peripheral tissue may provide valuable information when the analyses of the obtained dataset is guided by an a-priori hypothesis.