Udo Dannlowski1, Harald Kugel2, Dominik Grotegerd3, Ronny Redlich3, Nils Opel3, Katharina Dohm3, Dario Zaremba3, Anne Grögler3, Juliane Schwieren3, Thomas Suslow4, Patricia Ohrmann3, Jochen Bauer3, Axel Krug5, Tilo Kircher5, Andreas Jansen5, Katharina Domschke6, Christa Hohoff3, Pienie Zwitserlood7, Markus Heinrichs8, Volker Arolt3, Walter Heindel2, Bernhard T Baune9. 1. Department of Psychiatry, University of Münster, Münster; Department of Psychiatry, University of Marburg, Marburg. Electronic address: dannlow@uni-muenster.de. 2. Department of Clinical Radiology, University of Münster, Münster. 3. Department of Psychiatry, University of Münster, Münster. 4. Department of Psychosomatics and Psychotherapy, University of Leipzig, Leipzig. 5. Department of Psychiatry, University of Marburg, Marburg. 6. Department of Psychiatry, University of Würzburg, Würzburg. 7. Department of Psychology, University of Münster, Münster. 8. Department of Psychology, University Medical Center, University of Freiburg, Freiburg, Germany; Freiburg Brain Imaging Center, University Medical Center, University of Freiburg, Freiburg, Germany. 9. Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, Australia.
Abstract
BACKGROUND: Oxytocin has received much attention as a prosocial and anxiolytic neuropeptide. In human studies, the G-allele of a common variant (rs53576) in the oxytocin receptor gene (OXTR) has been associated with protective properties such as reduced stress response and higher receptiveness for social support. In contrast, recent studies suggest a detrimental role of the rs53576 G-allele in the context of childhood maltreatment. To further elucidate the role of OXTR, gene by maltreatment interactions on brain structure and function were investigated. METHODS: Three hundred nine healthy participants genotyped for OXTR rs53576 underwent structural as well as functional magnetic resonance imaging during a common emotional face-matching task. Childhood maltreatment was assessed with the Childhood Trauma Questionnaire (CTQ). Gray matter volumes were investigated by means of voxel-based morphometry across the entire brain. RESULTS: Structural magnetic resonance imaging data revealed a strong interaction of rs53576 genotype and CTQ scores, mapping specifically to the bilateral ventral striatum. GG homozygotes but not A-allele carriers showed strong gray matter reduction with increasing CTQ scores. In turn, lower ventral striatum gray matter volumes were associated with lower reward dependence, a prosocial trait. Furthermore, the G-allele was associated with increased amygdala responsiveness to emotional facial expressions. CONCLUSIONS: The findings suggest that the G-allele constitutes a vulnerability factor for specific alterations of limbic brain structure in individuals with adverse childhood experiences, complemented by increased limbic responsiveness to emotional interpersonal stimuli. While oxytocinergic signaling facilitates attachment and bonding in supportive social environments, this attunement for social cues may turn disadvantageous under early adverse conditions.
BACKGROUND: Oxytocin has received much attention as a prosocial and anxiolytic neuropeptide. In human studies, the G-allele of a common variant (rs53576) in the oxytocin receptor gene (OXTR) has been associated with protective properties such as reduced stress response and higher receptiveness for social support. In contrast, recent studies suggest a detrimental role of the rs53576 G-allele in the context of childhood maltreatment. To further elucidate the role of OXTR, gene by maltreatment interactions on brain structure and function were investigated. METHODS: Three hundred nine healthy participants genotyped for OXTRrs53576 underwent structural as well as functional magnetic resonance imaging during a common emotional face-matching task. Childhood maltreatment was assessed with the Childhood Trauma Questionnaire (CTQ). Gray matter volumes were investigated by means of voxel-based morphometry across the entire brain. RESULTS: Structural magnetic resonance imaging data revealed a strong interaction of rs53576 genotype and CTQ scores, mapping specifically to the bilateral ventral striatum. GG homozygotes but not A-allele carriers showed strong gray matter reduction with increasing CTQ scores. In turn, lower ventral striatum gray matter volumes were associated with lower reward dependence, a prosocial trait. Furthermore, the G-allele was associated with increased amygdala responsiveness to emotional facial expressions. CONCLUSIONS: The findings suggest that the G-allele constitutes a vulnerability factor for specific alterations of limbic brain structure in individuals with adverse childhood experiences, complemented by increased limbic responsiveness to emotional interpersonal stimuli. While oxytocinergic signaling facilitates attachment and bonding in supportive social environments, this attunement for social cues may turn disadvantageous under early adverse conditions.
Authors: Tania M Pollok; Anna Kaiser; Eline J Kraaijenvanger; Maximilian Monninger; Daniel Brandeis; Tobias Banaschewski; Simon B Eickhoff; Nathalie E Holz Journal: Neurosci Biobehav Rev Date: 2022-02-18 Impact factor: 9.052
Authors: Danielle A Baribeau; Annie Dupuis; Tara A Paton; Stephen W Scherer; Russell J Schachar; Paul D Arnold; Peter Szatmari; Rob Nicolson; Stelios Georgiades; Jennifer Crosbie; Jessica Brian; Alana Iaboni; Jason Lerch; Evdokia Anagnostou Journal: Sci Rep Date: 2017-09-14 Impact factor: 4.379