title: Startle gating deficits in a large cohort of patients with schizophrenia: relationship to medications, symptoms, neurocognition, and level of function.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Cross-sectional comparison of patients with schizophrenia and normal comparison subjects.
  
  
  METHODS
  University-based psychophysiology laboratory.
  
  
  METHODS
  Carefully screened patients with schizophrenia (n = 103) and normal comparison subjects (n = 66).
  
  
  METHODS
  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.
authors.affiliation: Departments of Psychiatry, School of Medicine, University of California-San Diego, La Jolla, CA 92093, USA. nswerdlow@ucsd.edu
authors.forename: Neal R
authors.initials: NR
authors.lastname: Swerdlow
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Light
authors.forename: Kristin S
authors.initials: KS
authors.lastname: Cadenhead
authors.forename: Joyce
authors.initials: J
authors.lastname: Sprock
authors.forename: Ming H
authors.initials: MH
authors.lastname: Hsieh
authors.forename: David L
authors.initials: DL
authors.lastname: Braff
mesh_terms: D000161:Acoustic Stimulation; D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001307:Auditory Perception / Q000502:physiology*; D003072:Cognition Disorders / Q000175:diagnosis* / Q000503:physiopathology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009433:Neural Inhibition / Q000502:physiology*; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D011930:Reaction Time / Q000502:physiology; D013216:Reflex, Startle / Q000502:physiology*; D012559:Schizophrenia / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology; D012565:Schizophrenic Psychology; D012737:Sex Factors; D012907:Smoking / Q000453:epidemiology
chemical_list: D014150:Antipsychotic Agents