Dysregulation of Olfactory Receptor Neuron Lineage in Schizophrenia

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Abstract
GROWING evidence from clinical and postmortem research implicates abnormal neurodevelopment in the pathogenesis of schizophrenia. One of the field's major challenges is to delineate abnormal neurodevelopmental processes that could culminate in the disease at the cellular and molecular level. For the neuropathologist, this would require either examination of brain tissue from fetuses destined for schizophrenia (impossible to know) or study of neural tissue in which there is ongoing neurogenesis from known patients with schizophrenia. Neurons in the nonhuman primate and human brain are born, migrate, and assume their mature phenotype in a complex and highly orchestrated process during fetal development and the immediate postnatal period.1-3 By the time the clinical expression of schizophrenia is apparent, neurogenesis and development is mostly complete. While there has recently been great interest in several small populations of proliferating cerebral neurons in adulthood,4 their functional destiny is unknown. By and large, the brain's neurons are morphologically static and molecularly homeostatic. Thus, it would seem as if the opportunity to examine developing neurons in schizophrenia is unavailable. However, components of the olfactory system, that is, the olfactory epithelium (OE) and its synaptic targets in the olfactory bulb provide an opportunity for a snapshot of morphologic and molecular neurodevelopmental processes that are ongoing even in late life.