The lifetime trajectory of schizophrenia and the concept of neurodevelopment

Defining the lifetime trajectory of schizophrenia and the mechanisms that drive it is one of the major challenges of schizophrenia research. Kraepelin assumed that the mechanisms were neurodegenerative (“dementia praecox”), and the early imaging work using computerized tomography seemed to support this model. Prominent ventricular enlargement and increased cerebrospinal fluid on the brain surface suggested that the brain had atrophied. In the 1980s, however, both neuropathological findings and evidence from magnetic resonance imaging (MRI) provided evidence suggesting that neurodevelopmental mechanisms might be a better explanation. This model is supported by both clinical and MRI evidence, particularly the fact that brain abnormalities are already present in first-episode patients. However, longitudinal studies of these patients have found evidence that brain tissue is also lost during the years after onset. The most parsimonious explanation of these findings is that neurodevelopment is a process that is ongoing throughout life, and that schizophrenia occurs as a consequence of aberrations in neurodevelopmental processes that could occur at various stages of life.