title: 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.
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.
authors.affiliation: University of Miami, Miller School of Medicine, Department of Psychiatry & Behavioral Sciences, Miami, FL, USA. Electronic address: amyers@med.miami.edu.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Myers
authors.affiliation: 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.
authors.forename: Leanne
authors.initials: L
authors.lastname: Williams
authors.affiliation: 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.
authors.forename: Justine M
authors.initials: JM
authors.lastname: Gatt
authors.affiliation: Neuroscience Research Australia, Randwick, Sydney, NSW 2031, Australia.
authors.forename: Erica Z
authors.initials: EZ
authors.lastname: McAuley-Clark
authors.affiliation: Neuroscience Research Australia, Randwick, Sydney, NSW 2031, Australia; School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Carol
authors.initials: C
authors.lastname: Dobson-Stone
authors.affiliation: Neuroscience Research Australia, Randwick, Sydney, NSW 2031, Australia; School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Schofield
authors.affiliation: University of Miami, Miller School of Medicine, Department of Psychiatry & Behavioral Sciences, Miami, FL, USA.
authors.forename: Charles B
authors.initials: CB
authors.lastname: Nemeroff
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001007:Anxiety / Q000235:genetics* / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003863:Depression / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008016:Life Change Events; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D018045:Receptors, Oxytocin / Q000235:genetics*; D013315:Stress, Psychological / Q000235:genetics* / Q000473:pathology; D011795:Surveys and Questionnaires
chemical_list: C569600:OXTR protein, human; D018045:Receptors, Oxytocin
keywords: Anxiety; DASS scale; Depression; Oxytocin; RNA expression; SNP; Stress