Schizophrenia: breakdown in the well-regulated lifelong process of brain development and maturation.

Recent evidence suggests that the temporal extent of brain development/maturation can be expanded into middle age when maximal white matter volume and myelination are reached in frontal lobes and association areas. This temporally expanded view of brain development underlies a more comprehensive conceptual model of schizophrenia that incorporates both the reduction of gray matter volume and the complementary expansion of white matter volume occurring from adolescence until middle age. The model posits that the brain is in a constant state of well-regulated structural and functional change roughly defined as periods of development continuing into middle age followed by degeneration. Multiple genetic and environmental factors can interfere with the developmental processes resulting in a dysregulation of the complementary changes occurring in gray and white matter. This dysregulation in development results in an insufficient capacity to maintain temporal synchrony of widely distributed neural networks and is manifested in the heterogeneity of symptoms and cognitive impairments of schizophrenia. The model highlights the contributory role of myelination to synchronous brain function, provides explanations for inconsistencies in the existing literature, and suggests testable hypotheses and novel approaches for intervention efforts.