The effect of polymorphisms in startle-related genes on anxiety symptom severity

Julia Tomasi; Clement C Zai; Gwyneth Zai; Deanna Herbert; Nicole King; Natalie Freeman; James L Kennedy; Arun K Tiwari

doi:10.1016/j.jpsychires.2020.03.019

The effect of polymorphisms in startle-related genes on anxiety symptom severity

J Psychiatr Res. 2020 Jun:125:144-151. doi: 10.1016/j.jpsychires.2020.03.019. Epub 2020 Apr 3.

Authors

Julia Tomasi¹, Clement C Zai², Gwyneth Zai³, Deanna Herbert⁴, Nicole King⁴, Natalie Freeman⁵, James L Kennedy⁶, Arun K Tiwari⁷

Affiliations

¹ Molecular Brain Science Department, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada. Electronic address: Julia.Tomasi@camh.ca.
² Molecular Brain Science Department, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
³ Molecular Brain Science Department, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; General Adult Psychiatry and Health Systems Division, CAMH, Toronto, ON, Canada.
⁴ Molecular Brain Science Department, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada.
⁵ Campbell Family Mental Health Research Institute and Krembil Centre for Neuroinformatics, CAMH, Toronto, ON, Canada.
⁶ Molecular Brain Science Department, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
⁷ Molecular Brain Science Department, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada. Electronic address: Arun.Tiwari@camh.ca.

PMID: 32289651
DOI: 10.1016/j.jpsychires.2020.03.019

Abstract

Given the limited effectiveness of treatments for pathological anxiety, there is a pressing need to identify genetic markers that can aid the precise selection of treatments and optimize treatment response. Anxiety and startle response levels demonstrate a direct relationship, and previous literature suggests that exaggerated startle reactivity may serve as an endophenotype of pathological anxiety. In addition, genetic variants related to startle reactivity may play a role in the etiology of pathological anxiety. In the current study, we selected 22 single nucleotide polymorphisms (SNPs) related to startle reactivity in the literature, and examined their association with anxiety symptom severity across psychiatric disorders (n = 508), and in a subset of patients with an anxiety disorder (n = 298). Overall, none of the SNPs pass correction for multiple independent tests. However, across psychiatric patients, rs6323 from the monoamine oxidase A (MAOA) gene and rs324981 from the neuropeptide S receptor 1 (NPSR1) gene were nominally associated with baseline anxiety symptom severity (p = 0.017, 0.023). These preliminary findings provide support for investigating startle-related genetic variants to identify biomarkers of anxiety symptom severity.

Keywords: Anxiety; Endophenotypes; Genetics; Single nucleotide polymorphisms; Startle response.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anxiety Disorders*
Anxiety* / genetics
Endophenotypes
Humans
Polymorphism, Single Nucleotide / genetics
Receptors, G-Protein-Coupled / genetics
Reflex, Startle / genetics

Substances

NPSR1 protein, human
Receptors, G-Protein-Coupled

Grants and funding

CIHR/Canada