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      Mechanisms of disturbed emotion processing and social interaction in borderline personality disorder: state of knowledge and research agenda of the German Clinical Research Unit

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          Abstract

          The last two decades have seen a strong rise in empirical research in the mechanisms of emotion dysregulation in borderline personality disorder. Major findings comprise structural as well as functional alterations of brain regions involved in emotion processing, such as amygdala, insula, and prefrontal regions. In addition, more specific mechanisms of disturbed emotion regulation, e.g. related to pain and dissociation, have been identified. Most recently, social interaction problems and their underlying neurobiological mechanisms, e.g. disturbed trust or hypersensitivity to social rejection, have become a major focus of BPD research. This article covers the current state of knowledge and related relevant research goals. The first part presents a review of the literature. The second part delineates important open questions to be addressed in future studies. The third part describes the research agenda for a large German center grant focusing on mechanisms of emotion dysregulation in BPD.

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          Most cited references181

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          The adolescent brain and age-related behavioral manifestations.

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          To successfully negotiate the developmental transition between youth and adulthood, adolescents must maneuver this often stressful period while acquiring skills necessary for independence. Certain behavioral features, including age-related increases in social behavior and risk-taking/novelty-seeking, are common among adolescents of diverse mammalian species and may aid in this process. Reduced positive incentive values from stimuli may lead adolescents to pursue new appetitive reinforcers through drug use and other risk-taking behaviors, with their relative insensitivity to drugs supporting comparatively greater per occasion use. Pubertal increases in gonadal hormones are a hallmark of adolescence, although there is little evidence for a simple association of these hormones with behavioral change during adolescence. Prominent developmental transformations are seen in prefrontal cortex and limbic brain regions of adolescents across a variety of species, alterations that include an apparent shift in the balance between mesocortical and mesolimbic dopamine systems. Developmental changes in these stressor-sensitive regions, which are critical for attributing incentive salience to drugs and other stimuli, likely contribute to the unique characteristics of adolescence.
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            Behavioural phenotyping assays for mouse models of autism.

            Autism is a heterogeneous neurodevelopmental disorder of unknown aetiology that affects 1 in 100-150 individuals. Diagnosis is based on three categories of behavioural criteria: abnormal social interactions, communication deficits and repetitive behaviours. Strong evidence for a genetic basis has prompted the development of mouse models with targeted mutations in candidate genes for autism. As the diagnostic criteria for autism are behavioural, phenotyping these mouse models requires behavioural assays with high relevance to each category of the diagnostic symptoms. Behavioural neuroscientists are generating a comprehensive set of assays for social interaction, communication and repetitive behaviours to test hypotheses about the causes of autism. Robust phenotypes in mouse models hold great promise as translational tools for discovering effective treatments for components of autism spectrum disorders.
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              Oxytocin modulates neural circuitry for social cognition and fear in humans.

              In non-human mammals, the neuropeptide oxytocin is a key mediator of complex emotional and social behaviors, including attachment, social recognition, and aggression. Oxytocin reduces anxiety and impacts on fear conditioning and extinction. Recently, oxytocin administration in humans was shown to increase trust, suggesting involvement of the amygdala, a central component of the neurocircuitry of fear and social cognition that has been linked to trust and highly expresses oxytocin receptors in many mammals. However, no human data on the effects of this peptide on brain function were available. Here, we show that human amygdala function is strongly modulated by oxytocin. We used functional magnetic resonance imaging to image amygdala activation by fear-inducing visual stimuli in 15 healthy males after double-blind crossover intranasal application of placebo or oxytocin. Compared with placebo, oxytocin potently reduced activation of the amygdala and reduced coupling of the amygdala to brainstem regions implicated in autonomic and behavioral manifestations of fear. Our results indicate a neural mechanism for the effects of oxytocin in social cognition in the human brain and provide a methodology and rationale for exploring therapeutic strategies in disorders in which abnormal amygdala function has been implicated, such as social phobia or autism.
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                Author and article information

                Contributors
                christian.schmahl@zi-mannheim.de
                sabine.herpertz@uni-heidelberg.de
                Katja.Bertsch@med.uni-heidelberg.de
                gabi.ende@zi-mannheim.de
                herta.flor@zi-mannheim.de
                peter.kirsch@zi-mannheim.de
                stefanie.lis@zi-mannheim.de
                a.meyer-lindenberg@zi-mannheim.de
                marcella.rietschel@zi-mannheim.de
                miriam.schneider@zi-mannheim.de
                rainer.spanagel@zi-mannheim.de
                TreedRolf-Detlef.Treede@medma.uni-heidelberg.de
                martin.bohus@zi-mannheim.de
                Journal
                Borderline Personal Disord Emot Dysregul
                Borderline Personal Disord Emot Dysregul
                Borderline Personality Disorder and Emotion Dysregulation
                BioMed Central (London )
                2051-6673
                9 September 2014
                9 September 2014
                2014
                : 1
                : 12
                Affiliations
                [ ]Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health Mannheim, Medical Faculty Mannheim / Heidelberg University, J 5, 68159 Mannheim, Germany
                [ ]Department of General Psychiatry, Center of Psychosocial Medicine, Medical Faculty Heidelberg / Heidelberg University, Heidelberg, Germany
                [ ]Department of Neuroimaging, Central Institute of Mental Health Mannheim, Medical Faculty Mannheim / Heidelberg University, Mannheim, Germany
                [ ]Institute of Neuropsychology and Clinical Psychology, Central Institute of Mental Health Mannheim, Medical Faculty Mannheim / Heidelberg University, Mannheim, Germany
                [ ]Department of Clinical Psychology, Central Institute of Mental Health Mannheim, Medical Faculty Mannheim / Heidelberg University, Mannheim, Germany
                [ ]Department of Psychiatry and Psychotherapy, Central Institute of Mental Health Mannheim, Medical Faculty Mannheim / Heidelberg University, Mannheim, Germany
                [ ]Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
                [ ]Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim / Heidelberg University, Mannheim, Germany
                [ ]Department of Neurophysiology, Center for Biomedicine and Medical Technology Mannheim, Medical Faculty Mannheim / Heidelberg University, Mannheim, Germany
                Article
                12
                10.1186/2051-6673-1-12
                4579501
                26401296
                28eabae8-9abb-4929-8a81-afe893dc5280
                © Schmahl et al.; licensee BioMed Central Ltd. 2014

                This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 30 June 2014
                : 22 August 2014
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                Review
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                © The Author(s) 2014

                borderline personality disorder,emotion processing,social interaction,neuroimaging,genetics

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