One of the enduring puzzles about schizophrenia is the question of why it typically first occurs in late adolescence or early adulthood. Structural neuroimaging studies indicate that persons with schizophrenia show prominent progressive brain changes at this time. For example, Andreasen and colleagues1 recently reported on the largest longitudinal study to date looking at brain volume changes over time in a cohort of patients with schizophrenia who had a mean age at first episode of 25 years. They found decreases in multiple grey and white matter regions, and these changes were most pronounced early (2 yr) after intake for the first episode of psychosis. In addition, a meta-analysis of studies involving persons at high risk for schizophrenia reported baseline decreases in grey matter in frontal and temporal regions of those who later transition to psychosis.2 Almost invariably, any research paper discussing reasons for the age at onset of symptoms or the early grey matter changes during young adulthood in patients with schizophrenia will invoke abnormal synaptic pruning as a potential mechanism. But what do we actually know about synaptic pruning in patients with schizophrenia?
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