Leah H Rubin1, Jessica J Connelly2, James L Reilly3, C Sue Carter4, Lauren L Drogos5, Hossein Pournajafi-Nazarloo4, Anthony C Ruocco6, Sarah K Keedy7, Ian Matthew8, Neeraj Tandon9, Godfrey D Pearlson10, Brett A Clementz11, Carol A Tamminga12, Elliot S Gershon7, Matcheri S Keshavan8, Jeffrey R Bishop13, John A Sweeney12. 1. Department of Psychiatry, University of Illinois at Chicago, Chicago, IL. 2. Department of Psychology, University of Virginia, Charlottesville, VA. 3. Department of Psychiatry and Behavioral Sciences, Northwestern University, Chicago, IL. 4. Kinsey Institute, Bloomington, IN. 5. Department of Physiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, Alberta, Canada. 6. Department of Psychology, University of Toronto, Toronto, ON. 7. Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL. 8. Department of Psychiatry, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA. 9. Department of Psychiatry, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; Baylor College of Medicine, Houston, TX. 10. Departments of Psychiatry and Neurobiology, Yale University and Olin Neuropsychiatric Research Center, Hartford, CT. 11. Department of Psychology, University of Georgia, Athens, GA. 12. Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX. 13. Departments of Pharmacy and Psychiatry, University of Minnesota, Minneapolis, MN.
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 the OXTR start 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. CONCLUSION: DNA methylation of the OXTR site -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.
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 the OXTR start 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. CONCLUSION: DNA methylation of the OXTR site -934 was higher in schizophrenia spectrum than bipolarpatients. Among patients, it was linked to behavioral deficits in social cognition and neuroanatomic structures known to support emotion processing only in schizophrenia spectrum individuals.
Entities:
Keywords:
emotion recognition; epigenetics; oxytocin; psychosis; sex differences; structural imaging
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