Gene Promoter DNA Methylations and Their Relationships With Endophenotypes in Patients With Schizophrenia
Recruitment status was: Recruiting
|First Received Date ICMJE||May 26, 2011|
|Last Updated Date||June 27, 2012|
|Start Date ICMJE||August 2011|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT01362478 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Gene Promoter DNA Methylations and Their Relationships With Endophenotypes in Patients With Schizophrenia|
|Official Title ICMJE||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.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Observational Model: Case Control
Time Perspective: Prospective
|Target Follow-Up Duration||Not Provided|
|Biospecimen||Retention: Samples With DNA
Gene promoter DNA methylations
|Sampling Method||Non-Probability Sample|
|Study Population||schizophrenia patients|
|Intervention ICMJE||Not Provided|
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Unknown status|
|Estimated Enrollment ICMJE||120|
|Estimated Completion Date||July 2014|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||20 Years to 65 Years (Adult)|
|Accepts Healthy Volunteers||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Taiwan|
|Removed Location Countries|
|NCT Number ICMJE||NCT01362478|
|Other Study ID Numbers ICMJE||99083|
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|Plan to Share Data||Not Provided|
|IPD Description||Not Provided|
|Responsible Party||Chun-Hsin Chen, Taipei Medical University WanFang Hospital|
|Study Sponsor ICMJE||Taipei Medical University WanFang Hospital|
|Collaborators ICMJE||Not Provided|
|PRS Account||Taipei Medical University WanFang Hospital|
|Verification Date||June 2012|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP