Predictors and mechanisms of conversion to psychosis

Summary Background: Identifying predictors and elucidating mechanisms underlying onset of psychosis are critical for the development of preventive interventions. Methods: This paper reviews findings on risk prediction algorithms and potential mechanisms of onset in youth at clinical high-risk for psychosis. Results: An independently validated individualized risk calculator is available that incorporates risk factors from clinical, demographic, neurocognitive, and psychosocial assessments to predict likelihood of conversion to psychosis among individuals who meet criteria for a prodromal risk syndrome. At risk individuals who convert to psychosis show a steeper rate of gray matter reduction, most prominent in prefrontal cortex, compared with those who do not. Higher levels of pro-inflammatory cytokines at baseline predicted the accelerated reduction in prefrontal gray matter. These same markers are associated with microglial-mediated synaptic pruning and dendritic retraction in animal models. Conclusions: Processes that modulate microglial activation, such as dysregulated immune function and deficient synaptic plasticity, may represent convergent mechanisms that influence brain dysconnectivity and risk for onset of psychosis.