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      Lack of Association between Oxytocin Receptor (OXTR) Gene Polymorphisms and Alexithymia: Evidence from Patients with Obsessive-Compulsive Disorder

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          Abstract

          Oxytocin receptor gene single nucleotide polymorphisms have been associated with structural and functional alterations in brain regions, which involve social-emotional processing. Therefore, oxytocin receptor gene polymorphisms may contribute to individual differences in alexithymia, which is considered to be a dysfunction of emotional processing. The aim of this study was to evaluate the association between oxytocin receptor gene single nucleotide polymorphisms or haplotypes and alexithymia in patients with obsessive-compulsive disorder. We recruited 355 patients with obsessive-compulsive disorder (234 men, 121 women). Alexithymia was measured by using the Toronto Alexithymia Scale. We performed single-marker and haplotype association analyses with eight single nucleotide polymorphisms (rs237885, rs237887, rs2268490, rs4686301, rs2254298, rs13316193, rs53576, and rs2268498) in the oxytocin receptor gene. There were no significant associations between any of the eight single nucleotide polymorphism of the oxytocin receptor gene and alexithymia. In addition, a six-locus haplotype block (rs237885-rs237887-rs2268490-rs4686301-rs2254298-rs13316193) was not significantly associated with alexithymia. These findings suggest that genetic variations in the oxytocin receptor gene may not explain a significant part of alexithymia in patients with obsessive-compulsive disorder.

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          The challenge of translation in social neuroscience: a review of oxytocin, vasopressin, and affiliative behavior.

          Social neuroscience is rapidly exploring the complex territory between perception and action where recognition, value, and meaning are instantiated. This review follows the trail of research on oxytocin and vasopressin as an exemplar of one path for exploring the "dark matter" of social neuroscience. Studies across vertebrate species suggest that these neuropeptides are important for social cognition, with gender- and steroid-dependent effects. Comparative research in voles yields a model based on interspecies and intraspecies variation of the geography of oxytocin receptors and vasopressin V1a receptors in the forebrain. Highly affiliative species have receptors in brain circuits related to reward or reinforcement. The neuroanatomical distribution of these receptors may be guided by variations in the regulatory regions of their respective genes. This review describes the promises and problems of extrapolating these findings to human social cognition, with specific reference to the social deficits of autism. (c) 2010 Elsevier Inc. All rights reserved.
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            The neural basis of empathy.

            Empathy--the ability to share the feelings of others--is fundamental to our emotional and social lives. Previous human imaging studies focusing on empathy for others' pain have consistently shown activations in regions also involved in the direct pain experience, particularly anterior insula and anterior and midcingulate cortex. These findings suggest that empathy is, in part, based on shared representations for firsthand and vicarious experiences of affective states. Empathic responses are not static but can be modulated by person characteristics, such as degree of alexithymia. It has also been shown that contextual appraisal, including perceived fairness or group membership of others, may modulate empathic neuronal activations. Empathy often involves coactivations in further networks associated with social cognition, depending on the specific situation and information available in the environment. Empathy-related insular and cingulate activity may reflect domain-general computations representing and predicting feeling states in self and others, likely guiding adaptive homeostatic responses and goal-directed behavior in dynamic social contexts.
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              Oxytocin attenuates amygdala responses to emotional faces regardless of valence.

              Oxytocin is known to reduce anxiety and stress in social interactions as well as to modulate approach behavior. Recent studies suggest that the amygdala might be the primary neuronal basis for these effects. In a functional magnetic resonance imaging study using a double-blind, placebo-controlled within-subject design, we measured neural responses to fearful, angry, and happy facial expressions after intranasal application of 24 IU oxytocin compared with placebo. Oxytocin reduced right-sided amygdala responses to all three face categories even when the emotional content of the presented face was not evaluated explicitly. Exploratory whole brain analysis revealed modulatory effects in prefrontal and temporal areas as well as in the brainstem. Results suggest a modulatory role of oxytocin on amygdala responses to facial expressions irrespective of their valence. Reduction of amygdala activity to positive and negative stimuli might reflect reduced uncertainty about the predictive value of a social stimulus and thereby facilitates social approach behavior.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                23 November 2015
                2015
                : 10
                : 11
                : e0143168
                Affiliations
                [1 ]Department of Psychiatry, Bundang Jesaeng Hospital, Seongnam Gyeonggi, Republic of Korea
                [2 ]Department of Psychiatry, Graduate school, Yonsei University, Seoul, Republic of Korea
                [3 ]Interdisciplinary Program of Bioinformatics, Seoul National University, Seoul, Republic of Korea
                [4 ]Department of Psychiatry and Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
                NIMH, NIH, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: MJK SJK JIK KN. Performed the experiments: MJK SJK JIK. Analyzed the data: WK MJK SJK. Contributed reagents/materials/analysis tools: WK MJK SJK JIK KN. Wrote the paper: MJK SJK.

                Article
                PONE-D-15-10716
                10.1371/journal.pone.0143168
                4658073
                26599592
                e0ff83fc-e8e8-494c-80d9-d6d17eb860e7
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 11 March 2015
                : 2 November 2015
                Page count
                Figures: 2, Tables: 5, Pages: 12
                Funding
                This research was supported by a grant (to S. J. Kim) from the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0022363). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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                All relevant data are within the paper and its Supporting Information file.

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