Gene Promoter DNA Methylations and Their Relationships With Endophenotypes in Patients With Schizophrenia

Schizophrenia Clinical Trial

Official title:

Gene Promoter DNA Methylations and Their Relationships With Endophenotypes in Patients With Schizophrenia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01362478
• Other study ID #: 99083
• Status: Recruiting
• Phase: N/A
• First received: May 26, 2011
• Last updated: June 27, 2012
• Start date: August 2011
• Est. completion date: July 2014

Study information

• Verified date: June 2012
• Source: Taipei Medical University WanFang Hospital
• Contact: Chun-Hsin Chen, MD
• Phone: 886-2-29307930
• Email: chunhsin57[@]yahoo.com.tw
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Observational

Clinical Trial Summary

Schizophrenia is a disabling mental disease affecting about 1% of the worldwide population. There is an overall heritability estimate of 68% for the underlying liability to schizophrenia. Molecular epigenetic studies can overcome the complexities of traditional genetic studies and provide a new framework for the search of etiological factors in schizophrenia.

DNA methylation provides an example of an epigenetic process that affects gene expression. Several postmortem experiments have found that increased DNA methylation at the glutamic acid decarboxylase (GAD67) and reelin promoter, and hypomethylation of membrane-bound catechol-O-methyltransferase (MB-COMT) promoter gene in prefrontal cortex of schizophrenia patients.

Because it is impossible to obtain brain tissue from schizophrenia patients clinically, the peripheral blood mononuclear cell (PBMC) can partly represent the brain gene expression. It has been reported to use PBMC as biomarkers for epigenetic abnormalities, such as histone acetylation and methylation, in schizophrenia. To the investigators best knowledge, gene promoter DNA methylation abnormalities in schizophrenia have been limited to postmortem study. It warrants to studying the DNA methylation using schizophrenia's PBMC.

Recently, endophenotype strategy has emerged as an important tool in understanding the genetic architecture of schizophrenia. Some cognitive functions, such as attention and working memory (WM), have been used as candidate endophenotypes for genetic studies in schizophrenia. Synchronized GABA neurotransmission in the dorsolateral prefrontal cortex is required for adequate attention and working memory, suggesting that impairments in GABA-mediated inhibition in the prefrontal cortex could contribute to the endophenotype presentations in schizophrenia.

Description:

The study will be approved by Institutional Review Board of participated institutions before recruiting patients. We will recruit 60 patients with schizophrenia and 60 healthy control subjects after explaining the study goal and getting the informed consents.

We will evaluate the performance of continuous performance test (CPT) and working memory subset in Chinese version of WAIS-III in both case and control subjects. We will assay reelin, GAD, and MB-COMT gene promoter DNA methylation using methylation specific PCR (MSP) and quantify these gene expression using quantitative reverse transcription polymerase chain reaction (qRT-PCR).

Patients will be followed in one year and receive the same evaluation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: July 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 20 Years to 65 Years

Eligibility

Case

Inclusion Criteria:

• age 20-65 year-old

• fulfill DSM-IV criteria of schizophrenia

Exclusion Criteria:

• patients who are pregnant or have significant medical conditions

• unstable psychiatric features (e.g. suicidal), too agitation

• a history of substance abuse or drug addiction within the previous 6 months, with the exception of nicotine dependence.

Control

Inclusion Criteria:

• 20-65 year-old

Exclusion Criteria:

• to have major psychiatric disorder, such as schizophrenia, mood disorders, and substance use disorders, except nicotine

• to have family history of schizophrenia, mood disorders, and substance use disorders

• to have serious medical conditions

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Schizophrenia

Locations

Country	Name	City	State
Taiwan	Taipei Medical University - WanFang Hospital	Taipei
Taiwan	WanFang Hospital, Taipei Medical University	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
Taipei Medical University WanFang Hospital

Country where clinical trial is conducted

Taiwan,