Targeting synapses and myelin in the prevention of schizophrenia

Many of the functions that are mediated by the prefrontal cortex (PFC) are severely impaired in schizophrenia. The maturation of these functions takes place during late adolescence and early adulthood, which coincides with the period of time when overt symptomatology of schizophrenia most commonly emerges. Two developmental processes occurring during the periadolescence period appear to mediate the functional maturation of the PFC: pruning of exuberant synapses and myelination of axons. It has long been speculated in the literature that disturbances of these processes may result in dysfunction of the PFC and thereby trigger the emergence of symptoms and deficits of schizophrenia. Alternatively, but not mutually exclusively, it has also been suggested that these late developmental processes may not be aberrant but they “unmask” preexisting deficits in the PFC, resulting in the onset of symptoms. The important implication of both of these scenarios is that in either case the emergence of PFC functional disturbances and the onset of symptoms and deficits of schizophrenia would in theory be preventable by pharmacologic manipulation of the synaptic pruning and/or axonal myelination processes. Thus, better understanding of the cellular and molecular mechanisms that mediate these processes will provide truly novel insight into the therapeutics and prevention of schizophrenia.