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      Borderline personality disorder and childhood trauma: exploring the affected biological systems and mechanisms

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          Abstract

          Background

          According to several studies, the onset of the Borderline Personality Disorder (BPD) depends on the combination between genetic and environmental factors (GxE), in particular between biological vulnerabilities and the exposure to traumatic experiences during childhood. We have searched for studies reporting possible alterations in several biological processes and brain morphological features in relation to childhood trauma experiences and to BPD. We have also looked for epigenetic mechanisms as they could be mediators of the effects of childhood trauma in BPD vulnerability.

          Discussion

          We prove the role of alterations in Hypothalamic-Pituitary-Adrenal (HPA) axis, in neurotrasmission, in the endogenous opioid system and in neuroplasticity in the childhood trauma-associated vulnerability to develop BPD; we also confirm the presence of morphological changes in several BPD brain areas and in particular in those involved in stress response.

          Summary

          Not so many studies are available on epigenetic changes in BPD patients, although these mechanisms are widely investigated in relation to stress-related disorders. A better comprehension of the biological and epigenetic mechanisms, affected by childhood trauma and altered in BPD patients, could allow to identify “at high risk” subjects and to prevent or minimize the development of the disease later in life.

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          Most cited references93

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          A neurotrophic model for stress-related mood disorders.

          There is a growing body of evidence demonstrating that stress decreases the expression of brain-derived neurotrophic factor (BDNF) in limbic structures that control mood and that antidepressant treatment reverses or blocks the effects of stress. Decreased levels of BDNF, as well as other neurotrophic factors, could contribute to the atrophy of certain limbic structures, including the hippocampus and prefrontal cortex that has been observed in depressed subjects. Conversely, the neurotrophic actions of antidepressants could reverse neuronal atrophy and cell loss and thereby contribute to the therapeutic actions of these treatments. This review provides a critical examination of the neurotrophic hypothesis of depression that has evolved from this work, including analysis of preclinical cellular (adult neurogenesis) and behavioral models of depression and antidepressant actions, as well as clinical neuroimaging and postmortem studies. Although there are some limitations, the results of these studies are consistent with the hypothesis that decreased expression of BDNF and possibly other growth factors contributes to depression and that upregulation of BDNF plays a role in the actions of antidepressant treatment.
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            Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions.

            Although the fact that genetic predisposition and environmental exposures interact to shape development and function of the human brain and, ultimately, the risk of psychiatric disorders has drawn wide interest, the corresponding molecular mechanisms have not yet been elucidated. We found that a functional polymorphism altering chromatin interaction between the transcription start site and long-range enhancers in the FK506 binding protein 5 (FKBP5) gene, an important regulator of the stress hormone system, increased the risk of developing stress-related psychiatric disorders in adulthood by allele-specific, childhood trauma-dependent DNA demethylation in functional glucocorticoid response elements of FKBP5. This demethylation was linked to increased stress-dependent gene transcription followed by a long-term dysregulation of the stress hormone system and a global effect on the function of immune cells and brain areas associated with stress regulation. This identification of molecular mechanisms of genotype-directed long-term environmental reactivity will be useful for designing more effective treatment strategies for stress-related disorders.
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              Borderline personality disorder.

              Borderline personality disorder is characterised by a pervasive pattern of instability in affect regulation, impulse control, interpersonal relationships, and self-image. Clinical signs of the disorder include emotional dysregulation, impulsive aggression, repeated self-injury, and chronic suicidal tendencies, which make these patients frequent users of mental-health resources. Causal factors are only partly known, but genetic factors and adverse events during childhood, such as physical and sexual abuse, contribute to the development of the disorder. Dialectical behaviour therapy and psychodynamic partial hospital programmes are effective treatments for out-of-control patients, and drug therapy can reduce depression, anxiety, and impulsive aggression. More research is needed for the understanding and management of this disabling clinical condition. Current strategies are focusing on the neurobiological underpinnings of the disorder and the development and dissemination of better and more cost-effective treatments to clinicians.
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                Author and article information

                Contributors
                ncattane@fatebenefratelli.eu
                rrossi@fatebenefratelli.eu
                mlanfredi@fatebenefratelli.eu
                +44-0-20-7848 0352 , annamaria.cattaneo@kcl.ac.uk , acattaneo@fatebenefratelli.eu
                Journal
                BMC Psychiatry
                BMC Psychiatry
                BMC Psychiatry
                BioMed Central (London )
                1471-244X
                15 June 2017
                15 June 2017
                2017
                : 17
                : 221
                Affiliations
                [1 ]GRID grid.419422.8, Biological Psychiatry Unit, , IRCCS Istituto Centro San Giovanni di Dio - Fatebenefratelli, ; via Pilastroni 4, Brescia, Italy
                [2 ]GRID grid.419422.8, Psychiatry Unit, , IRCCS Istituto Centro San Giovanni di Dio - Fatebenefratelli, ; via Pilastroni 4, Brescia, Italy
                [3 ]ISNI 0000 0001 2322 6764, GRID grid.13097.3c, Stress, Psychiatry and Immunology Laboratory, Department of Psychological Medicine, , Institute of Psychiatry, King’s College London, ; 125 Coldharbour Lane, London, SE5 9NU UK
                [4 ]ISNI 0000 0001 2322 6764, GRID grid.13097.3c, Department of Psychological Medicine, , Institute of Psychiatry, Psychology and Neuroscience, King’s College London, ; 125 Coldharbour Lane, London, SE5 9NU UK
                Article
                1383
                10.1186/s12888-017-1383-2
                5472954
                28619017
                e70162da-3abb-40b6-a918-4af9746c07a4
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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
                : 7 February 2017
                : 6 June 2017
                Funding
                Funded by: Eranet-Neuron Grant
                Award ID: Inflame-D project
                Award Recipient :
                Funded by: Italian Ministry of Health
                Award ID: Ricerca corrente
                Award Recipient :
                Categories
                Debate
                Custom metadata
                © The Author(s) 2017

                Clinical Psychology & Psychiatry
                borderline personality disorder,childhood trauma,hpa axis,endogenous opioid system,neurotransmission,neuroplasticity,neuroimaging studies,epigenetic mechanisms

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