Startle gating deficits in a large cohort of patients with schizophrenia: relationship to medications, symptoms, neurocognition, and level of function.

CONTEXT Patients with schizophrenia exhibit deficits in automatic, preattentive sensorimotor gating (prepulse inhibition [PPI]) of the startle reflex. OBJECTIVE To assess the relationships between PPI deficits and demographic, clinical, neurocognitive, and functional status in a large cohort of patients with schizophrenia. DESIGN Cross-sectional comparison of patients with schizophrenia and normal comparison subjects. SETTING University-based psychophysiology laboratory. PARTICIPANTS Carefully screened patients with schizophrenia (n = 103) and normal comparison subjects (n = 66). MAIN OUTCOME MEASURES Participants were assessed in structured clinical interviews and tested in measures of acoustic startle PPI and neurocognition. The level of functioning was assessed in patients using validated scales. Analyses first compared all of the patients vs normal comparison subjects. Patients were then divided based on sex, medications, smoking status, and levels of PPI. The associations of PPI to clinical, neurocognitive, and functional variables were assessed using both continuous and categorical analyses. RESULTS Compared with normal comparison subjects, patients exhibited PPI deficits at 60-millisecond intervals but not at 30- or 120-millisecond intervals. In addition, patients exhibited deficits in neurocognition. Among patients, PPI levels were associated with sex (higher in men than in women), medication status (highest in patients treated with atypical antipsychotics), and smoking (higher in smokers than in nonsmokers). Compared with patients in the highest quartile of PPI, those in the lowest quartile of PPI were significantly more impaired on specific functional measures but did not differ in neurocognitive measures or symptom severity. The relationship between low PPI and functional impairment was most pronounced and orderly in male patients. CONCLUSIONS These findings highlight several important factors (sex, medications, and smoking status) that strongly impact the study and interpretation of PPI deficits in patient populations. These results also support the concept that deficient PPI is associated with impaired functional status in schizophrenia.