Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

Epigenetic Regulation of BDNF in Major Depression

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

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 Tiao-Lai Huang, 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 ]
    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 ]

    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 ]

    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

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)
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.


Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
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.

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 identifier: NCT01182103

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

Responsible Party: Tiao-Lai Huang, Head of Department of Psychiatry, Chang Gung Memorial Hospital 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

Keywords provided by Tiao-Lai Huang, Chang Gung Memorial Hospital:
Major depression
DNA methylation
Histone modification

Additional relevant MeSH terms:
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders processed this record on May 25, 2017