Epigenetic Regulation of BDNF in Major Depression

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by Chang Gung Memorial Hospital
Sponsor:
Information provided by (Responsible Party):
Tiao-Lai Huang, Chang Gung Memorial Hospital
ClinicalTrials.gov Identifier:
NCT01182103
First received: August 11, 2010
Last updated: April 30, 2013
Last verified: April 2013
  Purpose

The investigators will (1) detect the associations between BDNF DNA methylation, histone modification, depressive symptoms, suicidal behavior and antidepressant responses in major depressive 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 in Patients With Major Depression

Resource links provided by NLM:


Further study details as provided by Chang Gung Memorial Hospital:

Primary Outcome Measures:
  • BDNF DNA methylation, histone modification, blood BDNF protein and RNA and BDNF rs6265 gene [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • the associations between BDNF DNA methylation, histone modification, depressive symptoms, suicidal behavior and antidepressant responses in major depressive patients; the correlation between blood BDNF protein and RNA and BDNF rs6265 gene [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Biospecimen Retention:   Samples With DNA

Blood


Estimated Enrollment: 160
Study Start Date: August 2010
Estimated Study Completion Date: July 2013
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts
Major depressive patients
Healthy subjects

Detailed Description:

BDNF (brain-derived neurotrophic factor) had been chosen as a candidate gene for a development of major depression. 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01182103

Contacts
Contact: Tiao-Lai Huang, M.D. 886-7-7317123 ext 8753 a540520@adm.cgmh.org.tw

Locations
Taiwan
Department of Psychiatry, Chang Gung Memorial Hospital Recruiting
Kaohsiung, Taiwan, 833
Contact: Tiao-Lai Huang, M.D.    886-7-7317123 ext 8753    a540520@adm.cgmh.org.tw   
Principal Investigator: Tiao-Lai Huang, M.D.         
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
Last Updated: April 30, 2013
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
Mood Disorders
Mental Disorders

ClinicalTrials.gov processed this record on July 28, 2014