Epigenetic Regulation of BDNF in Major Depression

Major Depressive Disorder Clinical Trial

Official title:

Epigenetic Regulation of Brain-Derived Neurotropic Factor (BDNF) in Patients With Major Depression

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01182103
• Other study ID #: NSC99-2628-B-182-002-MY2
• Status: Completed
• Phase: N/A
• First received: August 11, 2010
• Last updated: July 24, 2014
• Start date: August 2010
• Est. completion date: May 2013

Study information

• Verified date: July 2014
• Source: Chang Gung Memorial Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: May 2013
• Est. primary completion date: July 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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.

Study Design

Observational Model: Case Control, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Locations

Country	Name	City	State
Taiwan	Department of Psychiatry, Chang Gung Memorial Hospital	Kaohsiung

Sponsors (1)

Lead Sponsor	Collaborator
Chang Gung Memorial Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Brain-derived Neurotrophic Factor (BDNF) DNA Methylation of Major Depressive Disorder (MDD) Patients and Healthy Controls	averaged percentage of methylation at each CpG site listed	2 years	Yes
Primary	Histone Modification of MDD Patients Before and After Treatment and With Healthy Controls	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.	2 years	Yes
Secondary	BDNF Levels of MDD Patients Before and After Treatment and Healthy Controls	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.	2 years	Yes