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

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.

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.