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. Turetsky; David L. Braff

doi:10.1016/j.schres.2013.12.004

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. Turetsky

David L. Braff

University of California at San Diego
Department of Pediatrics
Stanford University
University of Pennsylvania
University of California at Los Angeles
Department of Veterans Affairs
Department of Psychiatry and Behavioral Sciences
Harvard University
Department of Psychiatry and Biobehavioral Sciences
University of Washington
VA Puget Sound Health Care System
VISN 22
Department of Psychiatry
Beth Israel Deaconess Medical Center
Department of Psychiatry
Icahn School of Medicine at Mount Sinai
VA Medical Center
Department of Biostatistics
Institute for Genomic Medicine

Research output: Contribution to journal › Review article › peer-review

86 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 language	English
Pages (from-to)	503-512
Number of pages	10
Journal	Schizophrenia Research
Volume	152
Issue number	2-3
DOIs	https://doi.org/10.1016/j.schres.2013.12.004
State	Published - Feb 2014
Externally published	Yes

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.

Funding

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.

Funders	Funder number
National Institutes of Health
National Institute of Mental Health	R01MH065588
Johns Hopkins University	HHSN268200782096C

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Endophenotype
Genetics
Multi-site
Prepulse inhibition
Schizophrenia
Startle

Access to Document

10.1016/j.schres.2013.12.004

Cite this

Swerdlow, N. R., Light, G. A., Sprock, J., Calkins, M. E., Green, M. F., Greenwood, T. A., Gur, R. E., Gur, R. C., Lazzeroni, L. C., Nuechterlein, K. H., Radant, A. D., Ray, A., Seidman, L. J., Siever, L. J., Silverman, J. M., Stone, W. S., Sugar, C. A., Tsuang, D. W., Tsuang, M. T., ... Braff, D. L. (2014). Deficient prepulse inhibition in schizophrenia detected by the multi-site COGS. Schizophrenia Research, 152(2-3), 503-512. https://doi.org/10.1016/j.schres.2013.12.004

@article{cb8281ad1ec64562b12c4f23067c5f52,

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. {\texttimes}. 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.",

keywords = "Endophenotype, Genetics, Multi-site, Prepulse inhibition, Schizophrenia, Startle",

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

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. ",

year = "2014",

month = feb,

doi = "10.1016/j.schres.2013.12.004",

language = "אנגלית",

volume = "152",

pages = "503--512",

journal = "Schizophrenia Research",

issn = "0920-9964",

publisher = "Elsevier B.V.",

number = "2-3",

}

Swerdlow, NR, Light, GA, Sprock, J, Calkins, ME, Green, MF, Greenwood, TA, Gur, RE, Gur, RC, Lazzeroni, LC, Nuechterlein, KH, Radant, AD, Ray, A, Seidman, LJ, Siever, LJ, Silverman, JM, Stone, WS, Sugar, CA, Tsuang, DW, Tsuang, MT, Turetsky, BI & Braff, DL 2014, 'Deficient prepulse inhibition in schizophrenia detected by the multi-site COGS', Schizophrenia Research, vol. 152, no. 2-3, pp. 503-512. https://doi.org/10.1016/j.schres.2013.12.004

TY - JOUR

T1 - Deficient prepulse inhibition in schizophrenia detected by the multi-site COGS

AU - Swerdlow, Neal R.

AU - Light, Gregory A.

AU - Sprock, Joyce

AU - Calkins, Monica E.

AU - Green, Michael F.

AU - Greenwood, Tiffany A.

AU - Gur, Raquel E.

AU - Gur, Ruben C.

AU - Lazzeroni, Laura C.

AU - Nuechterlein, Keith H.

AU - Radant, Allen D.

AU - Ray, Amrita

AU - Seidman, Larry J.

AU - Siever, Larry J.

AU - Silverman, Jeremy M.

AU - Stone, William S.

AU - Sugar, Catherine A.

AU - Tsuang, Debby W.

AU - Tsuang, Ming T.

AU - Turetsky, Bruce I.

AU - Braff, David L.

N1 - 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.

PY - 2014/2

Y1 - 2014/2

N2 - 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.

AB - 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.

KW - Endophenotype

KW - Genetics

KW - Multi-site

KW - Prepulse inhibition

KW - Schizophrenia

KW - Startle

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DO - 10.1016/j.schres.2013.12.004

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C2 - 24405980

AN - SCOPUS:84892858363

SN - 0920-9964

VL - 152

SP - 503

EP - 512

JO - Schizophrenia Research

JF - Schizophrenia Research

IS - 2-3

ER -

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

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

Access to Document

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Cite this