Startle reactivity and prepulse inhibition in prodromal and early psychosis: effects of age, antipsychotics, tobacco and cannabis in a vulnerable population.

The use of biomarkers in the study of the prodrome and first episode of psychosis provides a means of not only identifying individuals at greatest risk for psychosis but also understanding neurodevelopmental abnormalities early in the course of illness. Prepulse inhibition (PPI), a marker that is deficient in schizophrenia and after developmental manipulations in animal models, was assessed in 75 early psychosis (EP), 89 at risk (AR) for psychosis and 85 comparison subjects (CS) at baseline and 6 months. Consistent with findings in chronic schizophrenia, PPI was stable with repeated assessment and EP subjects had reduced PPI but this was most evident in tobacco smokers. A significant positive PPI and age association in AR and EP samples, but not CS, demonstrated potential neurodevelopmental differences in early psychosis. Unexpected findings included the fact that medication naive EP subjects, as well as AR subjects who later developed psychosis, had greater PPI, introducing the possibility of early compensatory changes that diverge from findings in chronic patients. In addition, subjects with a history of cannabis use had greater startle reactivity while EP and AR subjects who used cannabis and were also taking an antipsychotic had greater PPI, again highlighting the potentially important cannabis/psychosis association.