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The role of hypothalamus–pituitary–adrenal genes and childhood trauma in borderline personality disorder

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A Letter to the Editor to this article was published on 20 October 2015

Abstract

Current knowledge suggests that borderline personality disorder (BPD) results from the interaction between genetic and environmental factors. Research has mainly focused on monoaminergic genetic variants and their modulation by traumatic events, especially those occurring during childhood. However, to the best of our knowledge, there are no studies on the genetics of hypothalamus–pituitary–adrenal (HPA) axis, despite its vulnerability to early stress and its involvement in BPD pathogenesis. The aim of this study was to investigate the contribution of genetic variants in the HPA axis and to explore the modulating effect of childhood trauma in a large sample of BPD patients and controls. DNA was obtained from a sample of 481 subjects with BPD and 442 controls. Case–control differences in allelic frequencies of 47 polymorphisms in 10 HPA axis genes were analysed. Modulation of genetic associations by the presence of childhood trauma was also investigated by dividing the sample into three groups: BPD with trauma, BPD without trauma and controls. Two FKBP5 polymorphisms (rs4713902-C and rs9470079-A) showed significant associations with BPD. There were also associations between BPD and haplotype combinations of the genes FKBP5 and CRHR1. Two FKBP5 alleles (rs3798347-T and rs10947563-A) were more frequent in BPD subjects with history of physical abuse and emotional neglect and two CRHR2 variants (rs4722999-C and rs12701020-C) in BPD subjects with sexual and physical abuse. Our findings suggest a contribution of HPA axis genetic variants to BPD pathogenesis and reinforce the hypothesis of the modulating effect of childhood trauma in the development of this disorder.

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Acknowledgments

This study was supported by Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) and by a grant from Instituto de Salud Carlos III (PI10/00253 and PI11/00725).

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Authors and Affiliations

  1. Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Institut d’Investigació Biomèdica - Sant Pau (IIB-Sant Pau), Av. Sant Antoni Mª Claret 167, 08025, Barcelona, Spain

    Ana Martín-Blanco, Joaquim Soler, Maria Jesús Arranz, Matilde Elices, Cristina Carmona, Joana Bauzà, Víctor Pérez & Juan C. Pascual

  2. Psychiatry and Legal Medicine Department, Universitat Autònoma de Barcelona, Campus de la UAB, Plaza Cívica, s/n, Bellaterra, 08193, Barcelona, Spain

    Ana Martín-Blanco, Marc Ferrer, Joaquim Soler, Daniel Vega, Natalia Calvo, Matilde Elices, Cristina Carmona, Joana Bauzà, Mónica Prat, Víctor Pérez & Juan C. Pascual

  3. Department of Psychiatry, Hospital Universitari Vall d’Hebron, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Paseo de la Vall d’Hebron 119-129, 08035, Barcelona, Spain

    Marc Ferrer, Natalia Calvo & Mónica Prat

  4. Fundació Docència i Recerca Mutua Terrassa, St. Antoni 19, 08221, Terrassa, Barcelona, Spain

    Maria Jesús Arranz

  5. Department of Psychiatry and Mental Health, Consorci Sanitari de l’Anoia, Avenida Catalunya 11, Igualada, 08700, Barcelona, Spain

    Daniel Vega

  6. Institut of Neurosciences, Universitat Autònoma de Barcelona, Campus de la UAB, Plaza Cívica, s/n, Bellaterra, 08193, Barcelona, Spain

    Daniel Vega

  7. Psychiatric Genetics Unit, Vall d’Hebron Research Institut, Hospital Universitari Vall d’Hebron, Paseo de la Vall d’Hebron 119-129, 08035, Barcelona, Spain

    Cristina Sanchez-Mora & Iris García-Martinez

  8. Genetics Department, Hospital de la Santa Creu i Sant Pau, U705, CIBERER, Av. Sant Antoni Mª Claret 167, 08025, Barcelona, Spain

    Juliana Salazar

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  1. Ana Martín-Blanco
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  2. Marc Ferrer
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  3. Joaquim Soler
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Correspondence to Juan C. Pascual.

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Martín-Blanco, A., Ferrer, M., Soler, J. et al. The role of hypothalamus–pituitary–adrenal genes and childhood trauma in borderline personality disorder. Eur Arch Psychiatry Clin Neurosci 266, 307–316 (2016). https://doi.org/10.1007/s00406-015-0612-2

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