Fig. 1.

Since schizophrenia has a specific developmental trajectory, with onset in late adolescence or early adulthood, it is reasonable to hypothesize that a combination of genetic and environmental factors that lead to elevated oxidative stress in neurons could produce oxidative damage and subsequent interneuron dysfunction in the young adult cortex. The cartoon represents some of the proposed stages in this process. First, oxidative stress may be present in cortical interneurons during development as a consequence of a combination of predisposing gene variations and environmental factors that may include immune activation and stress. Pervasive oxidative stress in fast-spiking interneurons may impair their function, but as this cell population is not fully mature until late adolescence, the outcome may only be a mild set of cognitive deficits not too different from what can be frequently observed in healthy populations. It is during the protracted developmental trajectory of these interneurons that their altered state may become evident in full-fledge behavioral anomalies. As interneurons can become strongly activated in the transition to adolescence to adulthood, sick interneurons may yield a cortical circuit with altered excitation-inhibition balance. Such state can be evidenced in abnormal electroencephalogram oscillations and may yield schizophrenia symptoms, primarily in the cognitive domain.