Tiffany A Greenwood1, Neal R Swerdlow1, Joyce Sprock1, Monica E Calkins2, Robert Freedman3, Michael F Green4, Raquel E Gur2, Ruben C Gur2, Laura C Lazzeroni5, Gregory A Light6, Keith H Nuechterlein7, Allen D Radant8, Jeremy M Silverman9, William S Stone10, Catherine A Sugar11, Debby W Tsuang8, Ming T Tsuang1, Bruce I Turetsky2, David L Braff1, Erica Duncan12. 1. Department of Psychiatry, University of California San Diego, La Jolla, CA, United States of America. 2. Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, United States of America. 3. Department of Psychiatry, University of Colorado Health Sciences Center, Denver, CO, United States of America. 4. VA Greater Los Angeles Healthcare System, Los Angeles, CA, United States of America; Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, United States of America. 5. Departments of Psychiatry and Behavioral Sciences and of Biomedical Data Science, Stanford University, Stanford, CA, United States of America; Department of Veterans Affairs Health Care System, Palo Alto, CA, United States of America. 6. Department of Psychiatry, University of California San Diego, La Jolla, CA, United States of America; VISN-22 Mental Illness, Research, Education and Clinical Center (MIRECC), VA San Diego Healthcare System, San Diego, CA, United States of America. 7. Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, United States of America. 8. VA Puget Sound Health Care System, Seattle, WA, United States of America; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, United States of America. 9. James J. Peters VA Medical Center, New York, NY, United States of America; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America. 10. Department of Psychiatry, Harvard Medical School, Boston, MA, United States of America; Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Boston, MA, United States of America. 11. Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, United States of America; Department of Biostatistics, University of California Los Angeles School of Public Health, Los Angeles, CA, United States of America. 12. Atlanta Veterans Affairs Healthcare System, Decatur, GA, United States of America; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States of America. Electronic address: erica.duncan@va.gov.
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. Published by Elsevier B.V.
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. Published by Elsevier B.V.
Authors: Monica E Calkins; Dorcas J Dobie; Kristin S Cadenhead; Ann Olincy; Robert Freedman; Michael F Green; Tiffany A Greenwood; Raquel E Gur; Ruben C Gur; Gregory A Light; Jim Mintz; Keith H Nuechterlein; Allen D Radant; Nicholas J Schork; Larry J Seidman; Larry J Siever; Jeremy M Silverman; William S Stone; Neal R Swerdlow; Debby W Tsuang; Ming T Tsuang; Bruce I Turetsky; David L Braff Journal: Schizophr Bull Date: 2006-10-11 Impact factor: 9.306
Authors: Neal R Swerdlow; Martin Weber; Ying Qu; Gregory A Light; David L Braff Journal: Psychopharmacology (Berl) Date: 2008-06-21 Impact factor: 4.530
Authors: Jonathan K Wynn; Michael E Dawson; Anne M Schell; Mark McGee; Dustin Salveson; Michael F Green Journal: Biol Psychiatry Date: 2004-03-01 Impact factor: 13.382