Variation in the oxytocin receptor gene is associated with increased risk for anxiety, stress and depression in individuals with a history of exposure to early life stress

Amanda J Myers; Leanne Williams; Justine M Gatt; Erica Z McAuley-Clark; Carol Dobson-Stone; Peter R Schofield; Charles B Nemeroff

doi:10.1016/j.jpsychires.2014.08.021

Variation in the oxytocin receptor gene is associated with increased risk for anxiety, stress and depression in individuals with a history of exposure to early life stress

J Psychiatr Res. 2014 Dec:59:93-100. doi: 10.1016/j.jpsychires.2014.08.021. Epub 2014 Sep 16.

Authors

Amanda J Myers¹, Leanne Williams², Justine M Gatt³, Erica Z McAuley-Clark⁴, Carol Dobson-Stone⁵, Peter R Schofield⁵, Charles B Nemeroff⁶

Affiliations

¹ University of Miami, Miller School of Medicine, Department of Psychiatry & Behavioral Sciences, Miami, FL, USA. Electronic address: amyers@med.miami.edu.
² The Brain Dynamics Centre, Sydney Medical School, University of Sydney, and Westmead Millennium Institute, Westmead Hospital, Westmead, NSW 2145, Australia; Department of Psychiatry and Behavioral Neuroscience, Stanford University, CA, USA.
³ The Brain Dynamics Centre, Sydney Medical School, University of Sydney, and Westmead Millennium Institute, Westmead Hospital, Westmead, NSW 2145, Australia; School of Psychology, University of New South Wales, Randwick, NSW 2052, Australia; Neuroscience Research Australia, Randwick, Sydney, NSW 2031, Australia.
⁴ Neuroscience Research Australia, Randwick, Sydney, NSW 2031, Australia.
⁵ Neuroscience Research Australia, Randwick, Sydney, NSW 2031, Australia; School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
⁶ University of Miami, Miller School of Medicine, Department of Psychiatry & Behavioral Sciences, Miami, FL, USA.

Abstract

Background: Oxytocin is a neuropeptide that is involved in the regulation of mood, anxiety and social biology. Genetic variation in the oxytocin receptor gene (OXTR) has been implicated in anxiety, depression and related stress phenotypes. It is not yet known whether OXTR interacts with other risk factors such as early life trauma to heighten the severity of experienced anxiety and depression.

Methods: In this study, we examined genotypes in 653 individuals and tested whether SNP variation in OXTR correlates with severity of features of self-reported experience on the Depression Anxiety and Stress Scale (DASS), and whether this correlation is enhanced when early life trauma is taken into account. We also assessed the effects of OXTR SNPs on RNA expression levels in two separate brain tissue cohorts totaling 365 samples.

Results: A significant effect of OXTR genotype on DASS anxiety, stress and depression scores was found and ELS events, in combination with several different OXTR SNPs, were significantly associated with differences in DASS scores with one SNP (rs139832701) showing significant association or a trend towards association for all three measures. Several OXTR SNPs were correlated with alterations in OXTR RNA expression and rs3831817 replicated across both sets of tissues.

Conclusions: These results support the hypothesis that the oxytocin system plays a role in the pathophysiology of mood and anxiety disorders.

Keywords: Anxiety; DASS scale; Depression; Oxytocin; RNA expression; SNP; Stress.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Anxiety / genetics*
Anxiety / pathology
Brain / metabolism
Brain / pathology
Depression / genetics*
Depression / pathology
Female
Gene Frequency
Genetic Predisposition to Disease
Genotype
Humans
Life Change Events*
Male
Polymorphism, Single Nucleotide / genetics*
Psychiatric Status Rating Scales
Receptors, Oxytocin / genetics*
Stress, Psychological / genetics*
Stress, Psychological / pathology
Surveys and Questionnaires

Substances

OXTR protein, human
Receptors, Oxytocin

Abstract

Publication types

MeSH terms

Substances

Grants and funding