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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2012 by Taipei Medical University WanFang Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Chun-Hsin Chen, Taipei Medical University WanFang Hospital
ClinicalTrials.gov Identifier:
NCT01362478
First received: May 26, 2011
Last updated: June 27, 2012
Last verified: June 2012

May 26, 2011
June 27, 2012
August 2011
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Complete list of historical versions of study NCT01362478 on ClinicalTrials.gov Archive Site
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Gene Promoter DNA Methylations and Their Relationships With Endophenotypes in Patients With Schizophrenia
Gene Promoter DNA Methylations and Their Relationships With Endophenotypes in Patients With Schizophrenia

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.

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.

Observational
Observational Model: Case Control
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:

Gene promoter DNA methylations

Non-Probability Sample

schizophrenia patients

Schizophrenia
Not Provided
  • Case group
  • Control group
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
120
July 2014
Not Provided

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
Both
20 Years to 65 Years
Yes
Contact: Chun-Hsin Chen, MD 886-2-29307930 ext 53961 chunhsin57@yahoo.com.tw
Taiwan
 
NCT01362478
99083
No
Chun-Hsin Chen, Taipei Medical University WanFang Hospital
Taipei Medical University WanFang Hospital
Not Provided
Principal Investigator: Chun-Hsin Chen Taipei Medical University WanFang Hospital
Taipei Medical University WanFang Hospital
June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP