Neuropsychiatric Mechanisms of Change in Mentalization Based Treatment of Borderline Personality Disorder (MENTAB)

NCT01720953 | Terminated

• 1 other identifier: SJ-311
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Purpose: Borderline personality disorder (BPD) is a complex psychiatric disease of uncertain aetiology and pathogenesis. A key mechanism of disease susceptibility and treatment response could be epigenetic changes in DNA methylation patterns. However, no study has yet demonstrated that psychotherapy can exert its therapeutic effect through epigenetic mechanisms. The main aim of this study is to analyze the promoter methylation pattern of genes considered to be related to the development and psychopathology of BPD, in particular the brain-derived neurotrophic factor (BDNF) and glucocorticoid receptor genes, and the effects of mentalization based treatment (MBT) on changes. Associations to changes in BDNF serum levels and salivary cortisol levels, as well as key components of BPD aetiology and core treatment targets in MBT, will also be investigated. Should epigenetic mechanisms have importance for BPD pathology and effects of treatment, there is potential use of DNA methylation patterns as valid biomarker measures of diagnosis, prognosis, and treatment response. Hypothesis: The formation and maintenance of symptoms in BPD is mediated through neuropsychiatric mechanisms that can be affected through psychological treatment. Specifically, aberrant epigenetic regulation of neuropsychiatric genes related to behavioural control and affect regulation, as well as BDNF and cortisol levels, is ameliorated by therapeutic processes. Method: Fifty female patients diagnosed with BPD will undergo a year of intensive MBT that is designed to target domains of BPD pathology. The patients will be assessed at baseline and every 6 months over the treatment period. Matched healthy control subjects will be assessed at 6 month intervals to compare changes in DNA methylation, BDNF serum levels, salivary cortisol levels, and neuropsychological test performance. To link components of the neuropsychiatric mechanisms underlying the onset of illness, course, and response to treatment, patients will undergo assessment of clinical symptoms, comorbidity patterns and psychosocial impairment. Patients and control subjects will at baseline undergo assessment for childhood trauma, self-harm, suicidal behavior, early maladaptive schemas, and personality traits, and within the 1-year study period also undergo continuous assessment for changes in symptoms of dissociation, depression, and personality dysfunction.

Conditions

Borderline Personality Disorder

Keywords

Borderline Personality Disorder; Mentalization Based Therapy; DNA methylation; BDNF; Cortisol; Neuropsychology

Outcome Measures

Primary Outcomes (6)

• Promoter methylation pattern of genes considered to be related to the development and pathology of BPD, in particular the BDNF and glucocorticoid receptor genes

  Assessed at baseline, and after 6 and 12 months

• BDNF serum levels

  Assessed at baseline, and after 6 and 12 months

• Salivary cortisol levels

  Assessed at baseline, and after 6 and 12 months

• Neuropsychological test performance

  Assessed by a comprehensive battery of neuropsychological tests to measure both cognitive and emotion processing, including standard paper-and-pencil tests (WAIS-IV) and selected computerized tests (CANTAB, SuperLab and E-Prime). An interview will be conducted to assess autobiographical memory function.

  Assessed at baseline and after 12 months

• Psychopathology

  Measured by Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD), Hamilton Rating Scale for Depression (HAM-D), Symptom Checklist-90-Revised (SCL-90-R), Severity Indices of Personality Problems (SIPP-118), and Dissociative Experiences Scale - Brief (DES-B)

  Assessed before baseline, and after 6 and 12 months

• Affect regulation

  Measured by Affective Lability Scale (ALS-18), Barratt Impulsiveness Scale (BIS-11), Buss-Perry Aggression Questionnaire (BPAQ), Toronto Alexithymia Scale (TAS-20)

  Assessed at baseline, and after 6 and 12 months

Study Arms (1)

Healthy control subjects

Matched healthy control subjects will be assessed at 6 month intervals to compare changes in DNA methylation, BDNF serum levels, salivary cortisol levels, and neuropsychological test performance. Healthy control subjects will within the 1-year study period also undergo continuous assessment for comparative changes in symptoms of dissociation, depression, and personality dysfunction.

Other: Mentalization Based Therapy

Interventions

Mentalization Based Therapy OTHER

Fifty female patients diagnosed with BPD will undergo a year of intensive Mentalization Based Therapy that is designed to target domains of BPD pathology. The patients will be assessed at baseline and every 6 months over the treatment period.

Healthy control subjects

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Fifty female patients diagnosed with BPD, who will undergo a year of intensive Mentalization Based Therapy at the Psychiatric Clinic Roskilde, Denmark, and a matched healthy control subjects matched on age, gender and socioeconomic status.

You may qualify if:

• Female patients between the ages 18 - 40 with a clinical diagnosis of Borderline Personality Disorder to undergo a year of Mentalization Based Therapy at the Psychiatric Clinic Roskilde.

You may not qualify if:

• Severe comorbidity
• Serious medical condition
• Pregnancy
• Healthy control subjects:
• Match patients on age, gender, and socioeconomic status.
• Any mental disorder
• Serious medical condition
• Pregnancy

Sponsors & Collaborators

• Rune Andersen: lead
• Psychiatry Roskilde: collaborator
• University of Copenhagen: collaborator
• Psychiatric Epigenetics Laboratory, Institute of Psychiatry, UK: collaborator
• University of Southern Denmark: collaborator
• Psychoanalysis Unit, University College London, UK: collaborator
• Aarhus University Hospital: collaborator
• University College Zealand, Denmark: collaborator
• Research Division of Clinical Biochemistry, Koege Hospital, Denmark: collaborator

Study Sites (1)

Psychiatric Research Unit, Region Zeland

Roskilde, 4000, Denmark

Location

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood samples to measure DNA methylation and BDNF serum levels. Salivary samples to measure cortisol levels.

MeSH Terms

Conditions

Borderline Personality Disorder

Interventions

Mentalization-Based Therapy

Condition Hierarchy (Ancestors)

Personality Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Psychotherapy; Behavioral Disciplines and Activities

Study Officials

• Erik Simonsen, Professor, MD, Ph.D.

  Psychiatric Research Unit, Region Zealand, Denmark

  PRINCIPAL INVESTIGATOR

• Rune Andersen, Ph.D.

  Psychiatric Research Unit, Region Zealand, Denmark

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Senior researcher, Ph.D.

Study Record Dates

• First Submitted: October 26, 2012
• First Posted: November 2, 2012
• Study Start: October 1, 2012
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: July 25, 2014

Record last verified: 2014-07

Locations

DK (1)