Are common childhood or adolescent infections risk factors for schizophrenia and other psychotic disorders?

Postnatal infection may represent a preventable risk factor for onset of psychotic disorders in adolescence and early adulthood. The mechanism of action is likely to involve site-directed triggering of the brain's innate immune system, mediated principally through localised activation of microglial cells. This triggering may occur in response to systemic inflammatory stimuli, without direct involvement of the central nervous system. Microglial activation can represent a primary response or a secondary phenomenon at sites made vulnerable by prior injury; that is, areas containing previously activated microglia will respond more strongly to a new stimulus. The presence of activated microglia is indicative of a recent insult or active disease. It is not characteristic of long-established neurodevelopmental abnormalities. Activated microglia, acting through a variety of cytokine and other signal systems, have the capacity to significantly interfere with synaptic turnover and thus, over time, alter synaptic architecture and function. This pathophysiological path should be investigated more systematically as it may explain a novel "neuroprotective" mode of action for some existing antipsychotic compounds.