| Objective:To explore the contributions of genetic heterogeneity,drug plasma concentration and clinical features of patients to drug response in early-onset schizophrenia(EOS)patients with olanzapine monotherapy,finding the predictive factors on olanzepine treatment response in EOS.Methods:In this study we recruited 96 ICD-10 defined EOS patients who older than 7 years old and onset of illness before 17 years old,and all EOS patients received a 12-week systematic olanzepine titration treatment and a battery of assessments for treatment effect.Blood olanzepine plasma concentration were tested after 4-6 day when the optimal dose of olanapine was achieved,and genotyping of 9 polymorphisms of 3 genes(5-HT2A rs6313、rs6311、rs6314,DRD2 rs2514218、rs1799978、rs1800497、rs1801028、rs6277、COMT rs4680)were be conducted by MassArray genotyping technology.Positive and Negative Syndrome Scale(PANS S),Calgary Depression Scale for Schizophrenia(CDSS)and Personal and Social Performance(PSP)were applied at baseline and 1,2,4,6,8 and 12 weeks after treatment for assessing the patient’s psychotic symptoms,depressive symptoms,and social function,respectively.Results:(1)Study Population:Ninety-six patients were enrolled in this study.39(40.6%)were males and 57(59.4%)were females.The average age was 15.71±2.25 years.15 cases of EOS patients were younger than 13 years old who were defined as children group,and 81 cases of patients were older than 13 years old who were defined as teenage group.Wechsler children’s intelligence test scores ranged from 70-106 points,with x±SD of 85.37±8.59 for study sample.The daily olanzepine dose for majority patients were 5-20 mg:21 patients received a daily dose between 5-15mg per day,74 patients received a daily dose between 15-20mg per day,and only 1 patient received less than 5mg per day.Mean daily dose was 0.30±0.08mg/kg.(2)Improvement of clinical symptoms based on PANSS total score were defined as followed:26 cases(27.1%)were ineffective,51 cases(53.1%)were improved,19 cases(19.8%)were significantly improved,none was entirely cured,and the total effective rate was 72.9%(defined as responders).The total scores of PANSS,positive symptoms,negative symptoms,and CDSS scores were all significantly decreased after treatment(all P<0.01).One-way analysis of variance showed that there was a statistically significant difference on reduction rate of scores between positive symptoms and negative symptoms,and between common pathological symptoms and negative symptoms(P<0.05),suggesting that efficacy for positive symptoms and general pathological symptoms is both superior to negative symptoms.(3)There was a positive medium linear correlation between olanzapine daily dose(mg per kilogram)and olanzapine plasma concentrations(r=0.208,P=0.048).However,no correlation were found between efficacy and olanzapine plasma concentrations(r=-0.154,P=0.146).Besides,there was no difference on the olanzapine plasma concentration between responders and non-responders(P=0.951).No difference were found on olanzapine plasma concentrations between boys and girls,and between children group and teenager group.(both P>0.05).(4)Among 9 polymorphisms of 5-HT2A,DRD2 and COMT genes,patients with T/T genotype and C/T genotype of 5-HT2A rs6313 polymorphism had significant higher effective rate than those with C/C genotype,and patients with G/A genotype of 5-HT2A rs6311 polymorphism had significant higher effective rate than those with G/G genotype.(5)Binary logistic regression revealed that patients with higher IQ score,higher mother’s education level,negative family psychiatric history,and C/T genotype of 5-HT2A rs6313 than C/C genotype could predict be responding to olanzapine treatment.Conclusions:(1)12-week olanzapine monotherapy improve positive,negative,general pathological symptoms,depressive symptoms and social function of EOS patients in the sample of Yunnan Province.Improvement of positive and general pathological symptoms was better than that of negative symptoms.(2)Olanzapine plasma concentrations may increase along with the increase of olanzepin daily dose(mg per kilogram)in EOS.However,treatment efficacy does not elevated as olanzapine plasma concentrations going up.(3)Efficacy of olanzapine is influenced by inherent and non-inherent factors.Patients with T/T and C/T genotype of 5-HT2A rs6313,and with G/A genotype of 5-HT2A rs6311 polymorphism showed higher efficacy compared to their counterparts Higher IQ score,higher mother’s education level,negative family psychiatric history,and C/T genotype of 5-HT2A rs6313 could predict be responding to olanzapine treatment.However,the dose of olanzapine plasma concentrations could not predict the efficacy of olanzapine. |
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