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 nucleot...

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Bibliographic Details
Published in:Schizophrenia research 2014-02, Vol.152 (2), p.503-512
Main Authors: Swerdlow, Neal R, Light, Gregory A, Sprock, Joyce, Calkins, Monica E, Green, Michael F, Greenwood, Tiffany A, Gur, Raquel E, Gur, Ruben C, Lazzeroni, Laura C, Nuechterlein, Keith H, Radant, Allen D, Ray, Amrita, Seidman, Larry J, Siever, Larry J, Silverman, Jeremy M, Stone, William S, Sugar, Catherine A, Tsuang, Debby W, Tsuang, Ming T, Turetsky, Bruce I, Braff, David L
Format: Article
Language:English
Subjects:
Acoustic Stimulation
Adolescent
Adult
Adult and adolescent clinical studies
Aged
Analysis of Variance
Biological and medical sciences
Endophenotype
Female
Genetics
Humans
Male
Medical sciences
Middle Aged
Multi-site
Neural Inhibition - physiology
Prepulse inhibition
Psychiatric Status Rating Scales
Psychiatry
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Psychoses
Schizophrenia
Schizophrenia - physiopathology
Schizophrenic Psychology
Sensory Gating - physiology
Startle
Young Adult
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Summary: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.
ISSN:0920-9964
1573-2509
1573-2509
DOI:10.1016/j.schres.2013.12.004