Deficient prepulse inhibition in schizophrenia detected by the multi-site COGS

Neal R. Swerdlow, Gregory A. Light, Joyce Sprock, Monica E. Calkins, Michael F. Green, Tiffany A. Greenwood, Raquel E. Gur, Ruben C. Gur, Laura C. Lazzeroni, Keith H. Nuechterlein, Allen D. Radant, Amrita Ray, Larry J. Seidman, Larry J. Siever, Jeremy M. Silverman, William S. Stone, Catherine A. Sugar, Debby W. Tsuang, Ming T. Tsuang, Bruce I. TuretskyDavid L. Braff

Research output: Contribution to journalReview articlepeer-review

79 Scopus citations

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. Discussion: 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.

Original languageEnglish
Pages (from-to)503-512
Number of pages10
JournalSchizophrenia Research
Volume152
Issue number2-3
DOIs
StatePublished - Feb 2014
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by grants R01-MH065571 , R01-MH065588 , R01-MH065562 , R01-MH065707 , R01-MH065554 , R01-MH065578 , R01-MH065558 , R01 MH86135 , and K01-MH087889 from the National Institute of Mental Health . Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, Contract Number HHSN268200782096C.

Keywords

  • Endophenotype
  • Genetics
  • Multi-site
  • Prepulse inhibition
  • Schizophrenia
  • Startle

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