Ignite Creation Date:
2024-05-05 @ 11:36 PM
Last Modification Date:
2024-10-26 @ 10:36 AM
Study NCT ID:
NCT01362478
Status:
UNKNOWN
Last Update Posted:
2012-06-29
First Post:
2011-05-26
Brief Title:
Gene Promoter DNA Methylations and Their Relationships With Endophenotypes in Patients With Schizophrenia
Sponsor:
Taipei Medical University WanFang Hospital
Organization:
Taipei Medical University WanFang Hospital
Study Overview
Official Title:
Gene Promoter DNA Methylations and Their Relationships With Endophenotypes in Patients With Schizophrenia
Status:
UNKNOWN
Status Verified Date:
2012-06
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 schizophrenias 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
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 schizophrenias 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
Detailed 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
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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None