Epigenetic Regulation of BDNF in Major Depression

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tiao-Lai Huang, Chang Gung Memorial Hospital
ClinicalTrials.gov Identifier:
NCT01182103
First received: August 11, 2010
Last updated: July 24, 2014
Last verified: July 2014
  Purpose

The investigators will (1) detect the associations between brain-derived neurotrophic factor (BDNF) DNA methylation, histone modification, depressive symptoms, suicidal behavior and antidepressant responses in major depressive disorder (MDD) patients, (2) check the correlation between blood BDNF protein and RNA and BDNF rs6265 gene, and (3) discuss the possible mechanisms of epigenetic regulation of BDNF in Taiwanese major depressive patients.


Condition
Major Depressive Disorder

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: Epigenetic Regulation of Brain-Derived Neurotropic Factor (BDNF) in Patients With Major Depression

Further study details as provided by Chang Gung Memorial Hospital:

Primary Outcome Measures:
  • Brain-derived Neurotrophic Factor (BDNF) DNA Methylation of Major Depressive Disorder (MDD) Patients and Healthy Controls [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    averaged percentage of methylation at each CpG site listed

  • Histone Modification of MDD Patients Before and After Treatment and With Healthy Controls [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

    Chromatin immunoprecipitation (ChIP) was used to measure histone modification. The unit of our given machine is relative quantification, and a higher value indicated increased histone modification. The detailed method could be found in:

    Huebert DJ, Kamal M, O'Donovan A, Bernstein BE: Genome-wide analysis of histone modifications by ChIP-on-chip. Methods 2006; 40: 365-369.



Secondary Outcome Measures:
  • BDNF Levels of MDD Patients Before and After Treatment and Healthy Controls [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

    Serum BDNF levels were measured. MDD patients received antidepressant treatment, a standard biological management. Nothing novel (such as experimental drugs or management) is introduced in the treatment, so the research design is observational (of standard treatment).

    The choice of antidepressant drugs depended on the need of patients in natural treatment procedure. They included selective serotonin reuptake inhibitors (SSRI), eg. fluoxetine or paroxetine.



Biospecimen Retention:   Samples With DNA

Blood


Enrollment: 110
Study Start Date: August 2010
Study Completion Date: May 2013
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts
Major depressive patients
Healthy subjects

Detailed Description:

Brain-derived neurotrophic factor (BDNF) had been chosen as a candidate gene for a development of major depressive disorder (MDD). BDNF had been reported to have an important role on neuronal plasticity, axonal growth and connectivity, and participating in the local response to various types of neuronal stressors. BDNF also influences the differentiation of neurons.

In the past studies, the investigators had found that major depressive women had lower serum BDNF protein levels than healthy controls, and their BDNF levels became significantly increased after antidepressant treatments. In addition, some authors had found that reduced expression of BDNF was noted in postmortem brain of completed suicide subjects. Suicidal major depressive patients also had lower plasma BDNF levels than non-suicidal major depressive patients. These findings suggested that BDNF might play an important role in the suicidal behavior.

However, in past studies, the results did not fully explain why major depressive patients with same genotypes had different clinical expression, including the severity of depression, with/without suicide, and the treatment response. Recently, some papers found that there were relationships between epigenetic regulation, including DNA methylation and histone modification, and psychopathology of major depression. Therefore, we try to investigate the relationships between epigenetic regulation of BDNF and major depression.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

This 2-year study will be conducted in our clinical setting. By a semi-structured interview for DSM-IV criteria, a total of 160 subjectes (80 healthy controls and 80 patients with major depression) will be recruited in this study. In the first year (recruiting 40 healthy controls and 40 patients with major depression), the data of BDNF DNA methylation in all subjects will be collected. In the second year (recruiting another 40 healthy controls and 40 patients with major depression), the data of BDNF histone modification in all subjects will be collected and the mechanism of epigenetic regulation of BDNF in major depression will be discussed.

Criteria

Inclusion Criteria:

The clinical screening and assessment in patients with major depression:

  1. 40 major depression will be recruited in psychiatric inpatients according to DSM-IV criteria by a semi-structured interview. The assessment will be done by two senior psychiatrists. The intra-rater and inter-rater reliability will be done before this project started.
  2. The patients had the ability to complete the written inform consent.
  3. The choice of antidepressant drugs depended on the need of patients in natural treatment procedure. They included selective serotonin reuptake inhibitors (SSRI), eg. fluoxetine or paroxetine.
  4. The 17-item Hamilton Depression Rating Scale (HAM-D) was used to assess severity of depression. The minimum baseline score of the 17-item HAM-D was 18.

Exclusion Criteria:

  1. The patients had systemic diseases, including metabolic, heart, and liver diseases。
  2. The patients had received any drugs before entering this protocol.
  3. The patients were heavy smokers or dependent on alcohol.
  4. The use of secondary generation anti-psychotic drugs and mood stabilizers.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01182103

Locations
Taiwan
Department of Psychiatry, Chang Gung Memorial Hospital
Kaohsiung, Taiwan, 833
Sponsors and Collaborators
Chang Gung Memorial Hospital
Investigators
Principal Investigator: Tiao-Lai Huang, M.D. Chang-Gung Memorial Hospital, Kaohsiung
  More Information

No publications provided

Responsible Party: Tiao-Lai Huang, Head of Department of Psychiatry, Chang Gung Memorial Hospital
ClinicalTrials.gov Identifier: NCT01182103     History of Changes
Other Study ID Numbers: NSC99-2628-B-182-002-MY2
Study First Received: August 11, 2010
Results First Received: June 7, 2013
Last Updated: July 24, 2014
Health Authority: Taiwan: Department of Health

Keywords provided by Chang Gung Memorial Hospital:
Major depression
BDNF
DNA methylation
Histone modification

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mental Disorders
Mood Disorders

ClinicalTrials.gov processed this record on October 23, 2014