title: Association between methylation of the glucocorticoid receptor gene, childhood maltreatment, and clinical severity in borderline personality disorder.
abstract: The hypothalamus-pituitary-adrenal axis (HPA) is essential in the regulation of stress responses. Increased methylation of the promoter region of the glucocorticoid receptor gene (NR3C1) has been described both in subjects with history of childhood trauma and in patients with Borderline Personality Disorder (BPD). However, no data on the possible association between a higher methylation of this gene and clinical severity is available. The aim of this study was to evaluate the association between NR3C1 methylation status, the history of childhood trauma, and current clinical severity in subjects with BPD. A sample of 281 subjects with BPD (diagnosed by SCID-II and DIB-R semi-structured diagnostic interviews) was recruited. Clinical variables included previous hospitalizations, self-injurious behavior, and self-reported history of childhood trauma. DNA was extracted from peripheral blood. The results indicated a significant positive correlation between NR3C1 methylation status and childhood maltreatment (specifically physical abuse). In addition, a positive correlation between methylation status and clinical severity (DIB-R total score and hospitalizations) was observed. These findings suggest that NR3C1 methylation in subjects with BPD may be associated not only with childhood trauma but also with clinical severity, adding new evidence to the involvement of gene-environment interactions in this disorder.
authors.affiliation: Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Barcelona, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Institut d'Investigació Biomèdica - Sant Pau (IIB-Sant Pau), Spain; Psychiatry and Legal Medicine Department, Universitat Autònoma de Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Martín-Blanco
authors.affiliation: Psychiatry and Legal Medicine Department, Universitat Autònoma de Barcelona, Spain; Department of Psychiatry, Hospital Universitari de la Vall d'Hebron, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Ferrer
authors.affiliation: Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Barcelona, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Institut d'Investigació Biomèdica - Sant Pau (IIB-Sant Pau), Spain; Psychiatry and Legal Medicine Department, Universitat Autònoma de Barcelona, Spain.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Soler
authors.affiliation: Department of Genetics, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Juliana
authors.initials: J
authors.lastname: Salazar
authors.affiliation: Psychiatry and Legal Medicine Department, Universitat Autònoma de Barcelona, Spain; Department of Psychiatry, Hospital de Igualada (Consorci Sanitari de l'Anoia), Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Vega
authors.affiliation: Psychiatry and Legal Medicine Department, Universitat Autònoma de Barcelona, Spain; Department of Psychiatry, Hospital Universitari de la Vall d'Hebron, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Andión
authors.affiliation: Psychiatric Genetics Unit, Vall d'Hebron Research Institut, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sanchez-Mora
authors.affiliation: Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Barcelona, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Institut d'Investigació Biomèdica - Sant Pau (IIB-Sant Pau), Spain.
authors.forename: Maria Jesús
authors.initials: MJ
authors.lastname: Arranz
authors.affiliation: Psychiatric Genetics Unit, Vall d'Hebron Research Institut, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Ribases
authors.affiliation: Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Barcelona, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Institut d'Investigació Biomèdica - Sant Pau (IIB-Sant Pau), Spain; Psychiatry and Legal Medicine Department, Universitat Autònoma de Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Feliu-Soler
authors.affiliation: Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Barcelona, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Institut d'Investigació Biomèdica - Sant Pau (IIB-Sant Pau), Spain; Psychiatry and Legal Medicine Department, Universitat Autònoma de Barcelona, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: Pérez
authors.affiliation: Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Barcelona, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Institut d'Investigació Biomèdica - Sant Pau (IIB-Sant Pau), Spain; Psychiatry and Legal Medicine Department, Universitat Autònoma de Barcelona, Spain. Electronic address: jpascual@santpau.cat.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Pascual
mesh_terms: D000328:Adult; D001883:Borderline Personality Disorder / Q000235:genetics* / Q000523:psychology*; D002648:Child; D002649:Child Abuse / Q000523:psychology*; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D006760:Hospitalization; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D016728:Self-Injurious Behavior / Q000235:genetics; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: C497713:NR3C1 protein, human; D011965:Receptors, Glucocorticoid
keywords: Borderline personality disorder; Childhood trauma; Epigenetics; Genetics; Glucocorticoid receptor gene; Methylation