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

SCHIZOPHRENIA RESEARCH

卷:224

Article

Greenwood, Tiffany A.¹  Swerdlow, Neal R.¹  Sprock, Joyce¹  Calkins, Monica E.²  Freedman, Robert³  Green, Michael F.^4,5  Gur, Raquel E.²  Gur, Ruben C.²  Lazzeroni, Laura C.^6,7,8  Light, Gregory A.^1,9  Nuechterlein, Keith H.⁵  Radant, Allen D.^10,11  Silverman, Jeremy M.^12,13  Stone, William S.^14,15  Sugar, Catherine A.^5,16  Tsuang, Debby W.^10,11  Tsuang, Ming T.¹  Turetsky, Bruce, I²  Braff, David L.¹  Duncan, Erica^17,18 

[1] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA

[2] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA

[3] Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA

[4] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA

[5] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA

[6] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA

[7] Stanford Univ, Dept Biomed Data Sci, Stanford, CA 94305 USA

[8] Dept Vet Affairs Hlth Care Syst, Palo Alto, CA USA

[9] VA San Diego Healthcare Syst, VISN 22 Mental Illness Res Educ & Clin Ctr MIRECC, San Diego, CA USA

[10] VA Puget Sound Hlth Care Syst, Seattle, WA USA

[11] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA

[12] James J Peters VA Med Ctr, New York, NY USA

[13] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA

[14] Harvard Med Sch, Dept Psychiat, Boston, MA 02115 USA

[15] Beth Israel Deaconess Med Ctr, Publ Psychiat Div, Massachusetts Mental Hlth Ctr, Boston, MA 02215 USA

[16] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA

[17] Atlanta Vet Affairs Healthcare Syst, Decatur, GA USA

[18] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA

关键词: Schizophrenia;    Latency;    Heritability;    Acoustic startle;    Endophenotype;   

DOI  :  10.1016/j.schres.2020.11.003

来源: Elsevier

【 摘 要 】

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.y

【 授权许可】

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