Mapping the Consequences of Impaired Synaptic Plasticity in Schizophrenia through Development: An Integrative Model for Diverse Clinical Features

Abstract

Schizophrenia is associated with alterations in sensory, motor, and cognitive functions that emerge before psychosis onset; identifying pathogenic processes that can account for this multi-faceted phenotype remains a challenge. Accumulating evidence suggests that synaptic plasticity is impaired in schizophrenia. Given the role of synaptic plasticity in learning, memory, and neural circuit maturation, impaired plasticity may underlie many features of the schizophrenia syndrome. Here, we summarize the neurobiology of synaptic plasticity, review evidence that plasticity is impaired in schizophrenia, and explore a framework in which impaired synaptic plasticity interacts with brain maturation to yield the emergence of sensory, motor, cognitive, and psychotic features at different times during development in schizophrenia. Key gaps in the literature and future directions for testing this framework are discussed.