Heritability of acoustic startle magnitude and latency from the consortium on the genetics of schizophrenia

Tiffany A. Greenwood; Neal R. Swerdlow; Joyce Sprock; Monica E. Calkins; Robert Freedman; Michael F. Green; Raquel E. Gur; Ruben C. Gur; Laura C. Lazzeroni; Gregory A. Light; Keith H. Nuechterlein; Allen D. Radant; Jeremy M. Silverman; William S. Stone; Catherine A. Sugar; Debby W. Tsuang; Ming T. Tsuang; Bruce I. Turetsky; David L. Braff; Erica Duncan

doi:10.1016/j.schres.2020.11.003

Heritability of acoustic startle magnitude and latency from the consortium on the genetics of schizophrenia

Tiffany A. Greenwood
, Neal R. Swerdlow
, Joyce Sprock
, Monica E. Calkins
, Robert Freedman
, Michael F. Green
, Raquel E. Gur
, Ruben C. Gur
, Laura C. Lazzeroni
, Gregory A. Light
, Keith H. Nuechterlein
, Allen D. Radant
, Jeremy M. Silverman
, William S. Stone
, Catherine A. Sugar
, Debby W. Tsuang
, Ming T. Tsuang
, Bruce I. Turetsky
, David L. Braff
, Erica Duncan

University of California at San Diego
University of Pennsylvania
University of Colorado Anschutz Medical Campus
Department of Veterans Affairs
University of California at Los Angeles
Stanford University
VA Puget Sound Health Care System
University of Washington
VA Medical Center
Icahn School of Medicine at Mount Sinai
Harvard University
Beth Israel Deaconess Medical Center
Atlanta Veterans Affairs Health Care System
Emory University

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Background: Latency of the acoustic startle reflex is the time from presentation of the startling stimulus until the response, and provides an index of neural processing speed. Schizophrenia subjects exhibit slowed latency compared to healthy controls. One prior publication reported significant heritability of latency. The current study was undertaken to replicate and extend this solitary finding in a larger cohort. Methods: Schizophrenia probands, their relatives, and control subjects from the Consortium on the Genetics of Schizophrenia (COGS-1) were tested in a paradigm to ascertain magnitude, latency, and prepulse inhibition of startle. Trial types in the paradigm were: pulse-alone, and trials with 30, 60, or 120 ms between the prepulse and pulse. Comparisons of subject groups were conducted with ANCOVAs to assess startle latency and magnitude. Heritability of startle magnitude and latency was analyzed with a variance component method implemented in SOLAR v.4.3.1. Results: 980 subjects had analyzable startle results: 199 schizophrenia probands, 456 of their relatives, and 325 controls. A mixed-design ANCOVA on startle latency in the four trial types was significant for subject group (F(2,973) = 4.45, p = 0.012) such that probands were slowest, relatives were intermediate and controls were fastest. Magnitude to pulse-alone trials differed significantly between groups by ANCOVA (F(2,974) = 3.92, p = 0.020) such that controls were lowest, probands highest, and relatives intermediate. Heritability was significant (p < 0.0001), with heritability of 34–41% for latency and 45–59% for magnitude. Conclusion: Both startle latency and magnitude are significantly heritable in the COGS-1 cohort. Startle latency is a strong candidate for being an endophenotype in schizophrenia.

Original language	English
Pages (from-to)	33-39
Number of pages	7
Journal	Schizophrenia Research
Volume	224
DOIs	https://doi.org/10.1016/j.schres.2020.11.003
State	Published - Oct 2020
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2020

Funding

Supported by the National Institute of Mental Health ( R01-MH065571 , R01-MH065588 , R01-MH065562 , R01-MH065707 , R01-MH065554 , R01-MH065578 , R01-MH065558 , R01-MH086135 , and K01-MH087889 ), and a Veterans Affairs Merit Review grant ( I01CX000974 ). Infrastructure support was provided by the Office of Research and Development, the Mental Health Service Line, and the Center for Visual and Neurocognitive Rehabilitation at the Atlanta VA Health Care System, Decatur, GA. Additional infrastructure support was provided by the Department of Psychiatry and Behavioral Sciences of the Emory University School of Medicine, Atlanta, GA. Drs. Braff, Calkins, Greenwood, RE Gur, RC Gur, Lazzeroni, Radant, Silverman, Stone, Sugar, Swerdlow, D. Tsuang, M. Tsuang, and Turetsky and Ms. Sprock report no financial relationships with commercial interests. Dr. Green reports having been a consultant to Biogen, Click Therapeutics, Lundbeck, and Roche, and is a member of the scientific board for Cadent. Dr. Light reports consulting for Astellas Pharma, Inc., Heptares Therapeutics, NeuroSig, and Takeda Pharmaceutical Company, Ltd., and grants from Boerhinger Ingelheim. Dr. Nuechterlein has received unrelated research support from Janssen Scientific Affairs, Genentech, and Brain Plasticity, Inc., and has consulted to Genentech, Otsuka, and Brain Plasticity, Inc. Dr. Duncan has received research support for work unrelated to this project from Brain Plasticity, Inc., Auspex Pharmaceuticals, Inc. and Teva Pharmaceuticals, Inc. Dr. Duncan is a full-time attending psychiatrist in the Mental Health Service Line at the Atlanta VA Health Care System, Decatur, GA. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs. Supported by the National Institute of Mental Health (R01-MH065571, R01-MH065588, R01-MH065562, R01-MH065707, R01-MH065554, R01-MH065578, R01-MH065558, R01-MH086135, and K01-MH087889), and a Veterans Affairs Merit Review grant (I01CX000974).

Funders	Funder number
Boerhinger Ingelheim
Takeda Pharmaceutical Company, Ltd.
National Institute of Mental Health	R01-MH065707, K01-MH087889, R01-MH065562, R01-MH065578, R01-MH065558, R01-MH086135, R01MH065571, R01-MH065554, R01-MH065588
U.S. Department of Veterans Affairs
Genentech
Office of Research and Development
Nurses Organization of Veterans Affairs	I01CX000974
Department of Psychiatry and Behavioral Sciences, School of Medicine, Stanford University
Janssen Scientific Affairs

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

Acoustic startle
Endophenotype
Heritability
Latency
Schizophrenia

Access to Document

10.1016/j.schres.2020.11.003

Cite this

Greenwood, T. A., Swerdlow, N. R., Sprock, J., Calkins, M. E., Freedman, R., Green, M. F., Gur, R. E., Gur, R. C., Lazzeroni, L. C., Light, G. A., Nuechterlein, K. H., Radant, A. D., Silverman, J. M., Stone, W. S., Sugar, C. A., Tsuang, D. W., Tsuang, M. T., Turetsky, B. I., Braff, D. L., & Duncan, E. (2020). Heritability of acoustic startle magnitude and latency from the consortium on the genetics of schizophrenia. Schizophrenia Research, 224, 33-39. https://doi.org/10.1016/j.schres.2020.11.003

@article{f79218d84a2f48f3b58b9fc181145359,

title = "Heritability of acoustic startle magnitude and latency from the consortium on the genetics of schizophrenia",

abstract = "Background: Latency of the acoustic startle reflex is the time from presentation of the startling stimulus until the response, and provides an index of neural processing speed. Schizophrenia subjects exhibit slowed latency compared to healthy controls. One prior publication reported significant heritability of latency. The current study was undertaken to replicate and extend this solitary finding in a larger cohort. Methods: Schizophrenia probands, their relatives, and control subjects from the Consortium on the Genetics of Schizophrenia (COGS-1) were tested in a paradigm to ascertain magnitude, latency, and prepulse inhibition of startle. Trial types in the paradigm were: pulse-alone, and trials with 30, 60, or 120 ms between the prepulse and pulse. Comparisons of subject groups were conducted with ANCOVAs to assess startle latency and magnitude. Heritability of startle magnitude and latency was analyzed with a variance component method implemented in SOLAR v.4.3.1. Results: 980 subjects had analyzable startle results: 199 schizophrenia probands, 456 of their relatives, and 325 controls. A mixed-design ANCOVA on startle latency in the four trial types was significant for subject group (F(2,973) = 4.45, p = 0.012) such that probands were slowest, relatives were intermediate and controls were fastest. Magnitude to pulse-alone trials differed significantly between groups by ANCOVA (F(2,974) = 3.92, p = 0.020) such that controls were lowest, probands highest, and relatives intermediate. Heritability was significant (p < 0.0001), with heritability of 34–41\% for latency and 45–59\% for magnitude. Conclusion: Both startle latency and magnitude are significantly heritable in the COGS-1 cohort. Startle latency is a strong candidate for being an endophenotype in schizophrenia.",

keywords = "Acoustic startle, Endophenotype, Heritability, Latency, Schizophrenia",

author = "Greenwood, \{Tiffany A.\} and Swerdlow, \{Neal R.\} and Joyce Sprock and Calkins, \{Monica E.\} and Robert Freedman and Green, \{Michael F.\} and Gur, \{Raquel E.\} and Gur, \{Ruben C.\} and Lazzeroni, \{Laura C.\} and Light, \{Gregory A.\} and Nuechterlein, \{Keith H.\} and Radant, \{Allen D.\} 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.\} and Erica Duncan",

note = "Publisher Copyright: {\textcopyright} 2020",

year = "2020",

month = oct,

doi = "10.1016/j.schres.2020.11.003",

language = "אנגלית",

volume = "224",

pages = "33--39",

journal = "Schizophrenia Research",

issn = "0920-9964",

publisher = "Elsevier B.V.",

}

Greenwood, TA, Swerdlow, NR, Sprock, J, Calkins, ME, Freedman, R, Green, MF, Gur, RE, Gur, RC, Lazzeroni, LC, Light, GA, Nuechterlein, KH, Radant, AD, Silverman, JM, Stone, WS, Sugar, CA, Tsuang, DW, Tsuang, MT, Turetsky, BI, Braff, DL & Duncan, E 2020, 'Heritability of acoustic startle magnitude and latency from the consortium on the genetics of schizophrenia', Schizophrenia Research, vol. 224, pp. 33-39. https://doi.org/10.1016/j.schres.2020.11.003

TY - JOUR

T1 - Heritability of acoustic startle magnitude and latency from the consortium on the genetics of schizophrenia

AU - Greenwood, Tiffany A.

AU - Swerdlow, Neal R.

AU - Sprock, Joyce

AU - Calkins, Monica E.

AU - Freedman, Robert

AU - Green, Michael F.

AU - Gur, Raquel E.

AU - Gur, Ruben C.

AU - Lazzeroni, Laura C.

AU - Light, Gregory A.

AU - Nuechterlein, Keith H.

AU - Radant, Allen D.

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.

AU - Duncan, Erica

PY - 2020/10

Y1 - 2020/10

N2 - Background: Latency of the acoustic startle reflex is the time from presentation of the startling stimulus until the response, and provides an index of neural processing speed. Schizophrenia subjects exhibit slowed latency compared to healthy controls. One prior publication reported significant heritability of latency. The current study was undertaken to replicate and extend this solitary finding in a larger cohort. Methods: Schizophrenia probands, their relatives, and control subjects from the Consortium on the Genetics of Schizophrenia (COGS-1) were tested in a paradigm to ascertain magnitude, latency, and prepulse inhibition of startle. Trial types in the paradigm were: pulse-alone, and trials with 30, 60, or 120 ms between the prepulse and pulse. Comparisons of subject groups were conducted with ANCOVAs to assess startle latency and magnitude. Heritability of startle magnitude and latency was analyzed with a variance component method implemented in SOLAR v.4.3.1. Results: 980 subjects had analyzable startle results: 199 schizophrenia probands, 456 of their relatives, and 325 controls. A mixed-design ANCOVA on startle latency in the four trial types was significant for subject group (F(2,973) = 4.45, p = 0.012) such that probands were slowest, relatives were intermediate and controls were fastest. Magnitude to pulse-alone trials differed significantly between groups by ANCOVA (F(2,974) = 3.92, p = 0.020) such that controls were lowest, probands highest, and relatives intermediate. Heritability was significant (p < 0.0001), with heritability of 34–41% for latency and 45–59% for magnitude. Conclusion: Both startle latency and magnitude are significantly heritable in the COGS-1 cohort. Startle latency is a strong candidate for being an endophenotype in schizophrenia.

AB - Background: Latency of the acoustic startle reflex is the time from presentation of the startling stimulus until the response, and provides an index of neural processing speed. Schizophrenia subjects exhibit slowed latency compared to healthy controls. One prior publication reported significant heritability of latency. The current study was undertaken to replicate and extend this solitary finding in a larger cohort. Methods: Schizophrenia probands, their relatives, and control subjects from the Consortium on the Genetics of Schizophrenia (COGS-1) were tested in a paradigm to ascertain magnitude, latency, and prepulse inhibition of startle. Trial types in the paradigm were: pulse-alone, and trials with 30, 60, or 120 ms between the prepulse and pulse. Comparisons of subject groups were conducted with ANCOVAs to assess startle latency and magnitude. Heritability of startle magnitude and latency was analyzed with a variance component method implemented in SOLAR v.4.3.1. Results: 980 subjects had analyzable startle results: 199 schizophrenia probands, 456 of their relatives, and 325 controls. A mixed-design ANCOVA on startle latency in the four trial types was significant for subject group (F(2,973) = 4.45, p = 0.012) such that probands were slowest, relatives were intermediate and controls were fastest. Magnitude to pulse-alone trials differed significantly between groups by ANCOVA (F(2,974) = 3.92, p = 0.020) such that controls were lowest, probands highest, and relatives intermediate. Heritability was significant (p < 0.0001), with heritability of 34–41% for latency and 45–59% for magnitude. Conclusion: Both startle latency and magnitude are significantly heritable in the COGS-1 cohort. Startle latency is a strong candidate for being an endophenotype in schizophrenia.

KW - Acoustic startle

KW - Endophenotype

KW - Heritability

KW - Latency

KW - Schizophrenia

UR - https://www.scopus.com/pages/publications/85096134359

U2 - 10.1016/j.schres.2020.11.003

DO - 10.1016/j.schres.2020.11.003

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 33189519

AN - SCOPUS:85096134359

SN - 0920-9964

VL - 224

SP - 33

EP - 39

JO - Schizophrenia Research

JF - Schizophrenia Research

ER -

Heritability of acoustic startle magnitude and latency from the consortium on the genetics of schizophrenia

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Cite this