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Author Notes:

Correspondence: Erica Duncan, erica.duncan@va.gov

AS, TJ, KR, and ED designed the experiments.

AS, TJ, SN, BC, BB, KR, and ED performed the experiments.

AS, TJ, VK, AL, LG, SL, NM, BB, KR, and ED analyzed the data.

AS, LG, SL, and ED wrote the manuscript.

All authors edited and approved the manuscript.

ED is a full time attending psychiatrist, SN and BB are employees in the Mental Health Service Line, and NM is an employee of the Research and Development Service Line at the Atlanta Veterans Affairs Medical Center, Decatur, GA, USA.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Veterans Affairs.

Subjects:

Research Funding:

Infrastructure support was provided by Grady Hospital, Atlanta, GA, USA; the Research and Development and Mental Health Service Lines, Atlanta Veterans Affairs Medical Center, Decatur, GA, USA, and the Department of Psychiatry and Behavioral Sciences of the Emory University School of Medicine, Atlanta, GA, USA

This study was supported by the National Institute of Mental Health (MH071537 and MH096764 to KR, MH092576 to TJ, and MH085806 to AS), the Veterans Affairs Merit Review Program (ED), the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR000454, and an Emory University Research Committee Grant (URC grant to ED).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Psychiatry
  • acoustic startle
  • latency
  • genetics
  • schizophrenia
  • endophenotype
  • GENOME-WIDE ASSOCIATION
  • IMPAIRED PREPULSE INHIBITION
  • SCHIZOPHRENIC-PATIENTS
  • SPECTRUM DISORDERS
  • GATING DEFICITS
  • NRG1 GENE
  • NEUREGULIN-1
  • REFLEX
  • HABITUATION
  • LOCI

A Gene-Based Analysis of Acoustic Startle Latency

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Journal Title:

Frontiers in Psychiatry

Volume:

Volume 8, Number JUL

Publisher:

, Pages 117-117

Type of Work:

Article | Final Publisher PDF

Abstract:

Latency of the acoustic startle response is the time required from the presentation of startling auditory stimulus until the startle response is elicited and provides an index of neural processing speed. Latency is prolonged in subjects with schizophrenia compared to controls in some but not all studies and is 68-90% heritable in baseline startle trials. In order to determine the genetic association with latency as a potential inroad into genetically based vulnerability to psychosis, we conducted a gene-based study of latency followed by an independent replication study of significant gene findings with a single-nucleotide polymorphism (SNP)-based analysis of schizophrenia and control subjects. 313 subjects from an urban population of low socioeconomic status with mixed psychiatric diagnoses were included in the gene-based study. Startle testing was conducted using a Biopac M150 system according to our published methods. Genotyping was performed with the Omni-Quad 1M or the Omni Express BeadChip. The replication study was conducted on 154 schizophrenia subjects and 123 psychiatric controls. Genetic analyses were conducted with Illumina Human Omni1-Quad and OmniExpress BeadChips. Twenty-nine SNPs were selected from four genes that were significant in the gene-based analysis and also associated with startle and/or schizophrenia in the literature. Linear regressions on latency were conducted, controlling for age, race, and diagnosis as a dichotomous variable. In the gene-based study, 2,870 genes demonstrated the evidence of association after correction for multiple comparisons (false discovery rate < 0.05). Pathway analysis of these genes revealed enrichment for relevant biological processes including neural transmission (p = 0.0029), synaptic transmission (p = 0.0032), and neuronal development (p = 0.024). The subsequent SNP-based replication analysis revealed a strong association of onset latency with the SNP rs901561 on the neuregulin gene (NRG1) in an additive model (beta = 0.21, p = 0.001), indicating that subjects with the AA and AG genotypes had slower mean latency than subjects with GG genotype. In conclusion, startle latency, a highly heritable measure that is slowed in schizophrenia, may be a useful biological probe for genetic contributions to psychotic disorders. Our analyses in two independent populations point to a significant prediction of startle latency by genetic variation in NRG1.

Copyright information:

© 2017 Smith, Jovanovic, Kilaru, Lori, Gensler, Lee, Norrholm, Massa, Cuthbert, Bradley, Ressler and Duncan.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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