title: Sex and diagnosis specific associations between DNA methylation of the oxytocin receptor gene with emotion processing and temporal-limbic and prefrontal brain volumes in psychotic disorders.
abstract: BACKGROUND
  The oxytocin (OT) system, including receptor epigenetic mechanisms, has been shown to influence emotion processing, especially in females. Whether OT receptor (OXTR) epigenetic alterations occur across psychotic disorders in relation to illness-related disturbances in social cognition and brain anatomy is unknown.
  
  
  METHODS
  Participants with affective and nonaffective psychotic disorders (92 women, 75 men) and healthy controls (38 women, 37 men) from the Chicago site of the BSNIP study completed the Penn Emotion Recognition Test (ER-40), a facial emotion recognition task. We measured cytosine methylation at site -934 upstream of theOXTRstart codon in DNA from whole blood, and for the first time their relationship with plasma OT levels assessed by enzyme-immunoassay. Volumes of brain regions supporting social cognition were measured from MRI scans using FreeSurfer.
  
  
  RESULTS
  Patients with prototypic schizophrenia features showed higher levels of DNA methylation than those with prototypic bipolar features. Methylation was higher in women than men, and was associated with poorer emotion recognition only in female patients and controls. Greater methylation was associated with smaller volumes in temporal-limbic and prefrontal regions associated previously with social cognition, but only in healthy women and females with schizophrenia.
  
  
  CONCLUSIONS
  DNA methylation of theOXTRsite -934 was higher in schizophrenia spectrum than bipolar patients. Among patients, it was linked to behavioral deficits in social cognition and neuroanatomic structures known to support emotion processing only in schizophrenia spectrum individuals.
authors.affiliation: Department of Psychiatry, University of Illinois at Chicago, Chicago, IL.
authors.forename: Leah H
authors.initials: LH
authors.lastname: Rubin
authors.affiliation: Department of Psychology, University of Virginia, Charlottesville, VA.
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Connelly
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Northwestern University, Chicago, IL.
authors.forename: James L
authors.initials: JL
authors.lastname: Reilly
authors.affiliation: Kinsey Institute, Bloomington, IN.
authors.forename: C Sue
authors.initials: CS
authors.lastname: Carter
authors.affiliation: Department of Physiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, Alberta, Canada.
authors.forename: Lauren L
authors.initials: LL
authors.lastname: Drogos
authors.affiliation: Kinsey Institute, Bloomington, IN.
authors.forename: Hossein
authors.initials: H
authors.lastname: Pournajafi-Nazarloo
authors.affiliation: Department of Psychology, University of Toronto, Toronto, ON.
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Ruocco
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Keedy
authors.affiliation: Department of Psychiatry, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
authors.forename: Ian
authors.initials: I
authors.lastname: Matthew
authors.affiliation: Department of Psychiatry, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; Baylor College of Medicine, Houston, TX.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Tandon
authors.affiliation: Departments of Psychiatry and Neurobiology, Yale University and Olin Neuropsychiatric Research Center, Hartford, CT.
authors.forename: Godfrey D
authors.initials: GD
authors.lastname: Pearlson
authors.affiliation: Department of Psychology, University of Georgia, Athens, GA.
authors.forename: Brett A
authors.initials: BA
authors.lastname: Clementz
authors.affiliation: Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Tamminga
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL.
authors.forename: Elliot S
authors.initials: ES
authors.lastname: Gershon
authors.affiliation: Department of Psychiatry, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
authors.forename: Matcheri S
authors.initials: MS
authors.lastname: Keshavan
authors.affiliation: Departments of Pharmacy and Psychiatry, University of Minnesota, Minneapolis, MN.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Bishop
authors.affiliation: Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: John A
authors.initials: JA
authors.lastname: Sweeney
keywords: emotion recognition; epigenetics; oxytocin; psychosis; sex differences; structural imaging