Towards precision medicine in generalized anxiety disorder: Review of genetics and pharmaco(epi)genetics

Julia Tomasi; Amanda J Lisoway; Clement C Zai; Ricardo Harripaul; Daniel J Müller; Gwyneth C M Zai; Randi E McCabe; Margaret A Richter; James L Kennedy; Arun K Tiwari

doi:10.1016/j.jpsychires.2019.09.002

Towards precision medicine in generalized anxiety disorder: Review of genetics and pharmaco(epi)genetics

J Psychiatr Res. 2019 Dec:119:33-47. doi: 10.1016/j.jpsychires.2019.09.002. Epub 2019 Sep 6.

Authors

Affiliations

¹ Molecular Brain Science Department, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
² Molecular Brain Science Department, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 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 Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Molecular Neuropsychiatry & Development (MiND) Lab, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
⁴ Molecular Brain Science Department, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
⁵ Molecular Brain Science Department, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 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, Centre for Addiction and Mental Health, Toronto, ON, Canada.
⁶ Department of Psychiatry & Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada; Anxiety Treatment and Research Clinic, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada.
⁷ Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Frederick W. Thompson Anxiety Disorders Centre, Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
⁸ Molecular Brain Science Department, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada. Electronic address: arun.tiwari@camh.ca.

PMID: 31563039
DOI: 10.1016/j.jpsychires.2019.09.002

Abstract

Generalized anxiety disorder (GAD) is a prevalent and chronic mental disorder that elicits widespread functional impairment. Given the high degree of non-response/partial response among patients with GAD to available pharmacological treatments, there is a strong need for novel approaches that can optimize outcomes, and lead to medications that are safer and more effective. Although investigations have identified interesting targets predicting treatment response through pharmacogenetics (PGx), pharmaco-epigenetics, and neuroimaging methods, these studies are often solitary, not replicated, and carry several limitations. This review provides an overview of the current status of GAD genetics and PGx and presents potential strategies to improve treatment response by combining better phenotyping with PGx and improved analytical methods. These strategies carry the dual benefit of delivering data on biomarkers of treatment response as well as pointing to disease mechanisms through the biology of the markers associated with response. Overall, these efforts can serve to identify clinical, genetic, and epigenetic factors that can be incorporated into a pharmaco(epi)genetic test that may ultimately improve treatment response and reduce the socioeconomic burden of GAD.

Keywords: Endophenotypes; Generalized anxiety disorder; Pharmaco-epigenetics; Pharmacogenetics; Polygenic risk scores; Treatment response.

Publication types

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

MeSH terms

Anxiety Disorders* / diagnosis
Anxiety Disorders* / drug therapy
Anxiety Disorders* / genetics
Endophenotypes*
Epigenesis, Genetic*
Humans
Pharmacogenetics*
Precision Medicine*