The synaptic pathology of schizophrenia: is aberrant neurodevelopment and plasticity to blame?

Synaptic pathology is a feature of the brain in schizophrenia, denoted by alterations in the expression of synaptic proteins. In the absence of data indicative of neurodegenerative processes, the neuropathological features of schizophrenia suggest that the major pathogenic process in the disorder is one of aberrant development. Molecular evidence in support of a neurodevelopmental origin of schizophrenia has come from studies examining the expression of key developmental genes. However, as many of these genes are also involved in synaptic plasticity, their altered expression in schizophrenia also suggests that the disorder may be one of aberrant synaptic plasticity. The aim of this review is to explore whether aberrant development and synaptic plasticity may underlie the synaptic pathology of schizophrenia. It does this in two ways. First, studies in schizophrenia of the expression of two synaptic genes important in synaptic remodeling and plasticity are reviewed, changes in which may be indicative of aberrant synaptic plasticity in the disorder. Second, the possible relationship between the expression of genes involved in development and plasticity with that of presynaptic proteins is examined. Such a relationship, in combination with their altered expression in schizophrenia, may indicate whether developmental and plasticity-related processes may contribute to the synaptic pathology of the disorder. A brief discussion on the possible origins of the synaptic pathology of schizophrenia, and possible future studies, concludes the review.