title: Deficient prepulse inhibition in schizophrenia detected by the multi-site COGS.
abstract: BACKGROUND
  Startle inhibition by weak prepulses (PPI) is studied to understand the biology of information processing in schizophrenia patients and healthy comparison subjects (HCS). The Consortium on the Genetics of Schizophrenia (COGS) identified associations between PPI and single nucleotide polymorphisms in schizophrenia probands and unaffected relatives, and linkage analyses extended evidence for the genetics of PPI deficits in schizophrenia in the COGS-1 family study. These findings are being extended in a 5-site "COGS-2" study of 1800 patients and 1200 unrelated HCS to facilitate genetic analyses. We describe a planned interim analysis of COGS-2 PPI data.
  
  
  METHODS
  Eyeblink startle was measured in carefully screened HCS and schizophrenia patients (n=1402). Planned analyses of PPI (60 ms intervals) assessed effects of diagnosis, sex and test site, PPI-modifying effects of medications and smoking, and relationships between PPI and neurocognitive measures.
  
  
  RESULTS
  884 subjects met strict inclusion criteria. ANOVA of PPI revealed significant effects of diagnosis (p=0.0005) and sex (p<0.002), and a significant diagnosis×test site interaction. HCS>schizophrenia PPI differences were greatest among patients not taking 2nd generation antipsychotics, and were independent of smoking status. Modest but significant relationships were detected between PPI and performance in specific neurocognitive measures.
  
  
  CONCLUSIONS
  The COGS-2 multi-site study detects schizophrenia-related PPI deficits reported in single-site studies, including patterns related to diagnosis, prepulse interval, sex, medication and other neurocognitive measures. Site differences were detected and explored. The target COGS-2 schizophrenia "endophenotype" of reduced PPI should prove valuable for identifying and confirming schizophrenia risk genes in future analyses.
authors.affiliation: Department of Psychiatry, University of California San Diego, La Jolla, CA, United States. Electronic address: nswerdlow@ucsd.edu.
authors.forename: Neal R
authors.initials: NR
authors.lastname: Swerdlow
authors.affiliation: Department of Psychiatry, University of California San Diego, La Jolla, CA, United States; VISN 22, Mental Illness Research, Education & Clinical Center (MIRECC), VA San Diego Healthcare System, San Diego, CA, United States.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Light
authors.affiliation: Department of Psychiatry, University of California San Diego, La Jolla, CA, United States; VISN 22, Mental Illness Research, Education & Clinical Center (MIRECC), VA San Diego Healthcare System, San Diego, CA, United States.
authors.forename: Joyce
authors.initials: J
authors.lastname: Sprock
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, United States.
authors.forename: Monica E
authors.initials: ME
authors.lastname: Calkins
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States; VA Greater Los Angeles Healthcare System, Los Angeles, CA, United States.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Green
authors.affiliation: Department of Psychiatry, University of California San Diego, La Jolla, CA, United States.
authors.forename: Tiffany A
authors.initials: TA
authors.lastname: Greenwood
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, United States.
authors.forename: Raquel E
authors.initials: RE
authors.lastname: Gur
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, United States.
authors.forename: Ruben C
authors.initials: RC
authors.lastname: Gur
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United States; Department of Pediatrics, Stanford University, Stanford, CA, United States.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Lazzeroni
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States.
authors.forename: Keith H
authors.initials: KH
authors.lastname: Nuechterlein
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, United States; VA Puget Sound Health Care System, Seattle, WA, United States.
authors.forename: Allen D
authors.initials: AD
authors.lastname: Radant
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United States; Department of Pediatrics, Stanford University, Stanford, CA, United States.
authors.forename: Amrita
authors.initials: A
authors.lastname: Ray
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA, United States; Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Boston, MA, United States.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Seidman
authors.affiliation: Department of Psychiatry, The Mount Sinai School of Medicine, New York, NY, United States; James J. Peters VA Medical Center, New York, NY, United States.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Siever
authors.affiliation: Department of Psychiatry, The Mount Sinai School of Medicine, New York, NY, United States; James J. Peters VA Medical Center, New York, NY, United States.
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Silverman
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA, United States; Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Boston, MA, United States.
authors.forename: William S
authors.initials: WS
authors.lastname: Stone
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States; VISN 22, Mental Illness Research, Education & Clinical Center (MIRECC), VA San Diego Healthcare System, San Diego, CA, United States; Department of Biostatistics, University of California Los Angeles School of Public Health, Los Angeles, CA, United States.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Sugar
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, United States; VA Puget Sound Health Care System, Seattle, WA, United States.
authors.forename: Debby W
authors.initials: DW
authors.lastname: Tsuang
authors.affiliation: Department of Psychiatry, University of California San Diego, La Jolla, CA, United States; Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, United States; Harvard Institute of Psychiatric Epidemiology and Genetics, Boston, MA, United States.
authors.forename: Ming T
authors.initials: MT
authors.lastname: Tsuang
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, United States.
authors.forename: Bruce I
authors.initials: BI
authors.lastname: Turetsky
authors.affiliation: Department of Psychiatry, University of California San Diego, La Jolla, CA, United States; VISN 22, Mental Illness Research, Education & Clinical Center (MIRECC), VA San Diego Healthcare System, San Diego, CA, United States.
authors.forename: David L
authors.initials: DL
authors.lastname: Braff
mesh_terms: D000161:Acoustic Stimulation; D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009433:Neural Inhibition / Q000502:physiology*; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D055139:Sensory Gating / Q000502:physiology*; D055815:Young Adult
keywords: Endophenotype; Genetics; Multi-site; Prepulse inhibition; Schizophrenia; Startle