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

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.

Study Overview

• Status: Terminated
• Conditions: Borderline Personality Disorder
• Intervention / Treatment: Other: Mentalization Based Therapy

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

Study Locations

• Denmark
  • Roskilde, Denmark, 4000
    • Psychiatric Research Unit, Region Zeland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 36 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• 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.

Description

Patients:

Inclusion Criteria:

• 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.

Exclusion Criteria:

• Severe comorbidity
• Serious medical condition
• Pregnancy

Healthy control subjects:

Inclusion Criteria:

• Match patients on age, gender, and socioeconomic status.

Exclusion Criteria:

• Any mental disorder
• Serious medical condition
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Rune Andersen
• Collaborators: Aarhus University Hospital; University of Copenhagen; University of Southern Denmark; Psychiatry Roskilde; Psychiatric Epigenetics Laboratory, Institute of Psychiatry, UK; Psychoanalysis Unit, University College London, UK; University College Zealand, Denmark; Research Division of Clinical Biochemistry, Koege Hospital, Denmark
• Investigators: Principal Investigator: Erik Simonsen, Professor, MD, Ph.D., Psychiatric Research Unit, Region Zealand, Denmark; Study Chair: Rune Andersen, Ph.D., Psychiatric Research Unit, Region Zealand, Denmark

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Anticipated): December 1, 2016
• Study Completion (Anticipated): December 1, 2016

Study Registration Dates

• First Submitted: October 26, 2012
• First Submitted That Met QC Criteria: November 1, 2012
• First Posted (Estimate): November 2, 2012

Study Record Updates

• Last Update Posted (Estimate): July 25, 2014
• Last Update Submitted That Met QC Criteria: July 24, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Borderline Personality Disorder; Cortisol; Neuropsychology; BDNF; DNA methylation; Mentalization Based Therapy
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Personality Disorders; Disease; Borderline Personality Disorder
• Other Study ID Numbers: SJ-311