5-HTR2A, DRD2,and COMT Genes Polymorphisms and Olanzapine Plasma Concentration in Treatment of Early-onset Schizophrenia

Study Overview
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Brief Summary
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In this study,investigators will recruit 100 DSM-Ⅴdefined EOS Han patients, older than 7 years old and onset of illness before 17 years old, and all EOS patients will receive a 8-week systematic olanzepine titration treatment and a battery of assessments of treatment effect and safety. Blood olanzepine plasma concentration will be tested regularly and genotyping of 8 polymorphisms of 5-HTR2A, DRD2 and COMT genes will be conducted by Polymerase Chain Reaction （PCR）, Restriction Fragment Length Polymorphism (RFLP) and TaqMan probes genotyping technology. The aim of the study is to explore the predictive factors on olanzepine treatment response in EOS, which can guide the individualized treatment and improve the cure rate of EOS in clinical setting.

Detailed Description
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Early-onset schizophrenia (EOS) is the World Health Organization ranked psychosis as the third most disabling condition worldwide in youth, and may lead to obvious social dysfunction and interfere seriously with neurodevelopmental processes in a young person, which in turn has the potential to irreversibly alter the trajectory of his or her life. To improve the outcome of the patients of EOS, elaborate and individualized therapeutic regimen is urgently needed. The functional gene polymorphisms and drug (antipsychotics) plasma concentration can both influence the drug response, but few studies explore the contributions of genetic heterogeneity, drug plasma concentration and clinical features of patients to drug response together and interactions of above factors in EOS patients. In this study investigators will recruit 100 DSM-Ⅴdefined EOS Han patients, older than 7 years old and onset of illness before 17 years old, and all EOS patients will receive a 8-week systematic olanzepine titration treatment and a battery of assessments of treatment effect and safety. Blood olanzepine plasma concentration will be tested regularly and genotyping of 8 polymorphisms of 5-HTR2A, DRD2 and COMT genes will be conducted by Polymerase Chain Reaction （PCR）, Restriction Fragment Length Polymorphism (RFLP) and TaqMan probes genotyping technology. The aim of the study is to explore the predictive factors on olanzepine treatment response in EOS, which can guide the individualized treatment and improve the cure rate of EOS in clinical setting.

Official Title
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Effects of 5-HTR2A, DRD2,and COMT Genes Polymorphisms and Drug Plasma Concentration on Antipsychotic Response to Olanzapine in Treatment of Early-onset Schizophrenia

Conditions
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Early-onset Schizophrenia

Intervention / Treatment
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* Drug: olanzapine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: above 7 years old, age of onset ≤17 years old, Han or other nationality, male or female, in line with the diagnostic DSM-V criteria for schizophrenia, and negative and positive symptom scale (Positive and Negative Syndrome Scale, PANSS) score ≥70 points; patients are in the condition of first-episode, or relapse. Exclusion Criteria: IQ <70, current or previous history of traumatic brain injury, psychoactive substance use, personality disorders, obvious abnormalities on physical and laboratory examination, previous allergy or olanzapine had significant adverse reactions.

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br>All EOS patients will receive olanzapine treatment with flexible dose(2.5 to 20 mg/day)according to standard body weight,olanzapine will be initiated at 2.5 or 5 mg/day and the dose could be increased by 2.5 or 5 mg/day dose increments at the investigator's discretion.A effective dose would be titrated in two weeks with no tolerability or safety issues are apparent,the investigator could decrease the dose at any time and in any number of dose decrements if patients experienced an adverse event. | Drug: olanzapine<br>* olanzapine will be initiated at 2.5 or 5 mg/day according to patient's weight, and the dose could be increased by 2.5 or 5 mg every 4-7days at the investigator's discretion.A effective dose would be titrated in two weeks with no tolerability or safety issues are apparent,<br>* Other names: Zyprexa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| multiple regression equation of 5-HTR2A、DRD2 and COMT Genes Polymorphisms and Olanzapine Plasma Concentration and clinical features |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in score of PANSS |  | baseline and 12 weeks | 
| plateau concentration of olanzapine |  | 2 or 3,12 weeks | 
| change in Serum prolactin levels |  | 12 weeks | 
| Prevalence associated with age、gender and onset form |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Genes Polymorphisms, Plasma Concentration