Reduced prepulse inhibition in adolescents at risk for psychosis: a 2-year follow-up study

Background: Reduced prepulse inhibition (PPI) of the auditory startle reflex is a hallmark feature of attention-processing deficits in patients with schizophrenia and other psychotic disorders. Recent evidence suggests that these deficits may also be present before the onset of psychosis in individuals at ultra-high risk (UHR) and become progressively worse as psychosis develops. We conducted a longitudinal follow-up study to observe the development of PPI over time in UHR adolescents and healthy controls. Methods: Two-year follow-up data of PPI measures were compared between UHR adolescents and a matched control group of typically developing individuals. Results: We included 42 UHR adolescents and 32 matched controls in our study. Compared with controls, UHR individuals showed reduced PPI at both assessments. Clinical improvement in UHR individuals was associated with an increase in PPI parameters. Limitations: A developmental increase in startle magnitude partially confined the interpretation of the association between clinical status and PPI. Furthermore, post hoc analyses for UHR individuals who became psychotic between assessments had limited power owing to a low transition rate (14%). Conclusion: Deficits in PPI are present before the onset of psychosis and represent a stable vulnerability marker over time in UHR individuals. The magnitude of this marker may partially depend on the severity of clinical symptoms.