The schizophrenia brain is differentiated from the normal brain by subtle changes, with significant overlap in measures between normal and disease states. For the past 25 years, schizophrenia has increasingly been considered a neurodevelopmental disorder. This frame of reference challenges biological researchers to consider how pathological changes identified in adult brain tissue can be accounted for by aberrant developmental processes occurring during fetal, childhood or adolescent periods. The objective is to place schizophrenia neuropathology in a neurodevelopmental context.
This requires solid, scrutinized evidence of changes occurring during normal development of the cerebral cortex. We review literature on the development of the prefrontal cortex and chart major molecular and cellular events on a similar time line. Whilst neurogenesis, neuronal migration and myelination undergo most dramatic changes prenatally, these processes also extend into adolescence.
Expressions of inhibitory interneuron markers and GABA receptor subunits are dynamic, including during adolescence. While there are reports of synaptic regression throughout the first decade of life this has been balanced by evidence of dendritic growth and increase in expression of molecular markers of proteins required for excitatory synapse function until early adulthood. The NMDA receptor subunits reveal decreases, increases and constant level of mRNA expression in postnatal life. We conclude that the concepts around the timing of cortical neuronal migration, interneuron maturation and synaptic regression in humans may need revision and include greater emphasis on the protracted and dynamic changes occurring in the first decade of life and into adolescence.
