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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Schizophrenia

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Case group<br> | |
| Control group<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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schizophrenia, gene promoter, methylation, endophenotype, epigenetic