Epigenetic Regulation of BDNF in Schizophrenia

Epigenetic Regulation of BDNF and TrK B in Schizophrenic Patients

In this proposal, we will (1) detect the associations between BDNF and Trk B gene DNA methylation, histone modification, psychotic symptoms, obesity, suicide and antipsychotic drug responses in Taiwanese patients (2) discuss the possible mechanisms of epigenetic regulation of BDNF and Trk B in schizophrenia patients.

Study Overview

• Status: Completed
• Conditions: BDNF, DNA Methylation, Suicide, Drug Responses.

Detailed Description

A total 160 subjects (80 subjects every year, including 40 healthy controls and 40 schizophrenia patients) will be recruited during a 2-year period. The first year, the baseline data of BDNF and Trk B DNA methylation, protein and mRNA levels in all subjects will be collected and the following 1 months data will also be collected in schizophrenia with antipsychotic drug treatments. The second year, the baseline data of BDNF and Trk B histone modification in all subjects will be collected.

• Study Type: Observational
• Enrollment (Actual): 129

Contacts and Locations

Study Locations

• Taiwan
  • Kaohsiung, Taiwan, 833
    • Department of Psychiatry, Chang Gung Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

This study will be conducted in our clinical setting. By a semi-structured interview for DSM-IV criteria, total 160 subjectes (80 subjects every year, including 40 healthy controls and 40 schizophrenia patients with acute exacerbation) will be recurited during a 2-year period. The data of blood BDNF and Trk B DNA methylation and histone remodelling of all subjects will be collected.

Description

Inclusion Criteria:

-

1. The clinical screening and assessment in schizophrenic patients：

1. 40 schizophrenia patients will be recruited in psychiatric inpatients according to DSM-IV criteria (APA, 1994) by a structured interview (SCID). The assessment will be done by two senior psychiatrists. The intra-rater and inter-rater reliability will be done before this project started
2. age : 18-65 years old.
3. The patients had the ability to complete the written inform consent.。
4. The choice of antipsychotic drugs depended on the need of patients in natural treatment procedure. They included conventional drugs, eg.haloperidol 10-20 mg/day；SDA (serotonin dopamine antagonist) drug, eg. clozapine 100-400 mg/day or risperidone 3-6mg/day. The choice of the medication was according to the need of patients including previous responses and side effects.
5. PANSS (Positive and Negative Syndrome)(Kay, 1987,1988&1989) for positive, negative symptoms and severity.
6. Check body mass index (BMI): if BMI<24: normal; 24<BMI<27: overweight; BMI>27: obesity (Taiwan criteria, 2004). If the patients were overweight or obesity, the lipid profiles would be done and we would consult the experts to assess these patients. The condition for diet control and daily activity will be observed. If the condition was extremely abnormal, the case will be excluded.
7. Suicide behavior in tis study includes complete suicide and suicide attempt.

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.

Study Plan

How is the study designed?

Design Details

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

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Control; Healthy subjects
Schizophrenia; Schizophrenic patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
BDNF and Trk B DNA methylation, protein and mRNA levels	Two years

Secondary Outcome Measures

Outcome Measure	Time Frame
the associations between BDNF and Trk B gene DNA methylation, histone modification, psychotic symptoms, obesity, suicide and antipsychotic drug responses in Taiwanese patients	two years

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Investigators: Principal Investigator: Tiao-Lai Huang, M.D., Chang-Gung Memorial Hospital, Kaohsiung

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: November 25, 2009
• First Submitted That Met QC Criteria: November 27, 2009
• First Posted (Estimate): November 30, 2009

Study Record Updates

• Last Update Posted (Estimate): September 12, 2013
• Last Update Submitted That Met QC Criteria: September 11, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: schizophrenia, BDNF, DNA methylation, histone modification
• Additional Relevant MeSH Terms: Behavioral Symptoms; Self-Injurious Behavior; Suicide
• Other Study ID Numbers: CMRPG870951 and CMRPG870952