Neurodevelopment, neuroplasticity, and new genes for schizophrenia

Abstract

Schizophrenia is a complex, debilitating neuropsychiatric disorder. Epidemiological, clinical, neuropsychological, and neurophysiological studies have provided substantial evidence that abnormalities in brain development and ongoing neuroplasticity play important roles in the pathogenesis of the disorder. Complementing these clinical studies, a range of cytoarchitectural, morphometric, ultrastructural, immunochemical, and gene expression methods have been applied in investigations of postmortem brain tissues to characterize the cellular and molecular profile of putative developmental and plastic abnormalities in schizophrenia. While findings have been diverse and many are in need of replication, investigations focusing on higher cortical and limbic brain regions are increasingly demonstrating abnormalities in the structural and molecular integrity of the synaptic complex as well as glutamate-related receptors and signal transduction pathways that play critical roles in brain development, synaptogenesis, and synaptic plasticity. Most exciting have been recent associations of schizophrenia with specific genes, such as neuregulin-1, dysbindin-1, and AKT-1, which are vital to synaptic development, neurotransmission, and plasticity.