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. 2020 Oct:224:33-39.
doi: 10.1016/j.schres.2020.11.003. Epub 2020 Nov 12.

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

Tiffany A Greenwood  1 , Neal R Swerdlow  1 , Joyce Sprock  1 , Monica E Calkins  2 , Robert Freedman  3 , Michael F Green  4 , Raquel E Gur  2 , Ruben C Gur  2 , Laura C Lazzeroni  5 , Gregory A Light  6 , Keith H Nuechterlein  7 , Allen D Radant  8 , Jeremy M Silverman  9 , William S Stone  10 , Catherine A Sugar  11 , Debby W Tsuang  8 , Ming T Tsuang  1 , Bruce I Turetsky  2 , David L Braff  1 , Erica Duncan  12
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Heritability of acoustic startle magnitude and latency from the consortium on the genetics of schizophrenia

Tiffany A Greenwood et al. Schizophr Res. 2020 Oct.

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.

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Conflict of interest statement

Declaration of competing interest 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.

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