Microarray database mining and cell differentiation defects in schizophrenia

The causes of schizophrenia remain unknown, but a key role of oligodendrocytes and of the myelination process carried out by them has gained increasing support. The adult human brain parenchyma contains a relatively large population of progenitor cells that can generate oligodendrocytes. Defects in these adult oligodendrocyte progenitor cells (OPCs) or in their proliferation/differentiation have received little attention as potential causes of schizophrenia yet. We compared the set of genes whose expression is modified in schizophrenia, as revealed by our microarray studies, with genes specifically expressed in stem cells, as revealed by studies on human embryonic stem cells. We also evaluated the genes that are upregulated when stem cells engage in differentiation programs. These genes can be viewed as fingerprints or signatures for differentiation processes. The comparisons revealed that a substantial fraction of the genes downregulated in the brains of persons with schizophrenia belong to the differentiation signature. A plausible interpretation of our observations is that a cell differentiation process, possibly of adult OPCs to oligodendrocytes, is perturbed in schizophrenia. These observations constitute an incentive for a new direction of study, aimed at investigating the potential role of OPCs in schizophrenia.