Schizophrenia patients exhibit impairments in prepulse inhibition (PPI) of the acoustic startle response (ASR). PPI is commonly used as an index of sensorimotor gating. Results of animal studies and some human data suggest that PPI deficits are in part genetically determined, such that PPI could be an endophenotypic indicator of risk for schizophrenia, Thus, PPI deficits should already be present prior to onset of psychosis. To test this assumption, we investigated PPI in individuals with prodromal symptoms of schizophrenia and patients with first-episode schizophrenia.

Startle reactivity, habituation, and PPI of ASR were assessed in 54 subjects with prodromal symptoms of schizophrenia (35 at an early prodromal stage, 19 at a late prodromal stage), 31 first episode schizophrenic patients (14 unmedicated, 17 medicated), and 28 healthy controls. Patients were also examined with the Positive and Negative Symptom Scale and the Global Assessment of Functioning Scale.

Prodromal subjects and unmedicated patients with first episode schizophrenia showed significant PPI deficits, whereas schizophrenic patients treated with risperidone had almost normal PPI. In contrast, startle reactivity decreased with severity of symptoms but was relatively unimpaired in the medicated patients. With respect to habituation, prodromal subjects and schizophrenic patients did not differ from healthy controls.

PPI disruption is present in subjects in a prodromal state likely to proceed to schizophrenia, supporting the hypothesis that PPI disruption is an endophenotype of schizophrenia. In contrast, startle reactivity and habituation deficits were not evident in the prodromal subjects, but only in unmedicated patients with diagnosis of schizophrenia.