| Objective1-survery the polymorphism of disrupted-in-schizophrenia-1(DISCI) to discover its association with childhood schizophrenia.2.measurd the brain structure and research the premorbid abnormal behavior in childhood schizophrenia. Discuss the relationship of brain structure and premaorbid abnormal behavior with DISC1gene polymorphism.Methods1-With the method of case-control study.333childhood schizophrenia patients were chosen as the research objects.Meanwhile,272healthy persons as the control group I,310healthy students in primary and secondary school as the control group Ⅱ.2.The SNPrs821597in DISCI gene was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in study group, and so was the control group.3.The brain structures of patients whose course less than twelve months were measured by magnetic resonance imaging (MRI). And the measurement indexes were comprised of transverse diameter of third ventricle, distance from lateral wall of third ventricle to left surface of insula and from lateral wall of third ventricle to right surface of insula, width of lateral ventricle anterior horn, largest width of lateral ventricle body, left horn of temporal, right horn of temporal, width of frontal sulci, width of parietal sulci, width of interhemispheric fissure, width of left lateral fissure, width of right lateral fissure, width of left head of caudate nucleus, width of right head of caudate nucleus and depth of corpus callosum.4.Retrospective the patients and control group Ⅱ’s neurobehavioral characters aged from6to11years old according to their parants’memories with the Child Behavior Checklist (CBCL). The rating scales conclude social competences and behavior problems. The former contend three foctors as activity, sociability and school situation. And the latter one was subdivided into seven syndrome scales:the cleavage coercion, the depressive, the hyperactivity, somatic complaints, social withdrawn, aggressive behavior and delinquent behavior.5.Comparesion the differences of the genotypic frequency and allele frequency in rs821597between the study group and the control group by chi-square test. Covariance analysis, rank sum test were used in turn to analyze the difference of brain structure measurement values, premorbid abnormal behavior among patients with different genotypes.Nonparameter test was used to analyze the different of premorbid abnormal behavior between study group and control group.The correlation between brain structure and premorbid abnormal was test by Spearman rank correlation annlysis.Results1-The trilateral relationship in the gene polymorphism of rs8215978in DISCI in childhood schizophreniaThe results showed that rs821597had strong association with schizophrenia comparisoned with the controllers I (genotype:;r=6.45,df=2,P=.04; allele:;r=6.03, df=1, P=0.01;OR=1.33,95%CI=1.06～1.67). There are three genotypes that A/A, A/G, G/G in patient group and the control group I (30.0%,47.2%,22.8%;21.3%,50.4%,28.3%).2.The relationship of DISCI gene polymorphism with brain structure in childhood schizophreniaCovariance analysis the difference of brain structure in patients:there were significant difference among transverse diameter of third ventricle(F=6.75), width of left horn of temporal (F=3.18), width of left and right lateral fissure (F=14.78,3.64), width of parietal sulci (F=4.62), width of interhemispheric fissure (F=4.24) and width of left head of caudate nucleus (F=3.28) in the survey group with differ genotypes (P<0.05, P<0.01),which was analyzed by covariance statistics (age was made as the covariant). Pairwise comparison of the different genotypes in the study group:the AA genotype carriers had significantly higher transverse diameter of third ventricle than AG (q=0.77), GG (q=0.77), the AA and AG genotype carriers had significantly higher width of left horn of temporal, width of left lateral fissure, width of right lateral fissure and width of interhemispheric fissure than GG genotype carriers (q=0.51,0.39;2.07,2.03;1.37,0.91;0.57,0.50);AA,AG genotype carriers had higher width of parietal sulci than the GG ones (q=0.53,0.52); AA carriers had lower width of right head of caudate nucleus comparison with GG carriers (q=-1.41).And these differences were significant.(P<0.05, P<0.01)3.Comparesion the different of premorbid abnormal social competence and behavior problems in childhood schizophreniaThere are signigicantly different in premorbid abnormal social competence and behavior problems between the patients and the control group II.4.The relationship between the DISCI gene SNP rs821597polymorphism and premorbid abnormal behavior in childhood schizophreniaNonparameter test shows that,there were significantly different in activity(Z=-2.54),school situation(Z=-2.42),social competence(Z=-2.24), depression(Z=-2.37), social withdrawl(Z=-2.67),aggression(Z=-3.30) and the total score of behavior problems (Z=-3.44)between the study group and control group Ⅱ.The rank sum test shows that, Contrast the different of premorbid abnormal behavior among patients with different genotypes:total social competence (χ2=3.21, P=0.04), hyperactivity (χ2=12.27, P=0.00), social withdrawal (χ2=6.11, P=0.03) were significantly different (P<0.05, P<0.01). Pairwise comparison of the different genotypes: The AA genotype carriers had significantly lower score of social competence than AG and GG genotypes, and significantly higher score of hyperactivity and social withdrawal.5.The association of brain structure measurement values and premorbid abnormal behavior in childhood schizophrenia①the relationship between brain structure and social competence:there were significantly different in the transverse diameter of third ventricle(F=13.96), width of left head of caudate nucleus (F=6.43) and depth of corpus callosum (F=8.70) between high and low group of social compentence (P<0.05,P<0.01) analyzed by covariance.Spearman rank correlation analysis showed that the social competence score had significantly positively correlation with width of left and head of caudate nucleus and the depth of corpus callosum (r=0.17,0.17;P<0.01);activity score had significantly negtively correlation with the transverse diameter of third ventricle (r=-0.14;P<0.01), and positively correlation with the depth of corpus callosum (r=0.15;P<0.01);sociability had significantly positively correlation with distance from lateral wall of third ventricle to left surface of insulam, width of left head of caudate nucleus (r=0.18,0.20;P<0.01),and significantly negatively correlation with width of frontal sulci (r=0.15;P<0.01); the school situation score had significantly positively correlation with right surface of insulam, width of lateral ventricle anterior horn, width of left and right head of caudate nucleus (r=0.14,0.18,0.27,0.31;P<0.01).(2)the relationship between brain structure and behavior problems:take age as the covariates, covariance analysis showed that between the high and low score group, the transverse diameter of third ventricle, distance from lateral wall of third ventricle to right surface of insulam, width of left right head of caudate nucleus and the depth of corpus callosum was significantly different (P<0.05, P<0.01). Spearman rank correlation analysis showed that the total score of behavior promble had significantly positively correlation with the transverse diameter of third ventricle (r=0.29;P<0.01),and negatively correlation with width of left and right head of caudate nucleus and the depth of corpus callosum (r=-0.24,-0.21,-0.21;P<0.01); the cleavage coercion had significantly positively correlation with the transverse diameter of third ventricle,width of interhemispheric fissure (r=0.27,0.18;P<0.01), negatively correlation with the depth of corpus callosum (r=-0.27;P<0.01); the depressison had significantly positively correlation with the transverse diameter of third ventricle (r=0.19;P<0.01), negatively correlation width of left and right head of caudate nucleus (r=-0.16,-0.17;P<0.01); somatic complains had significantly positively correlation with and right horn of temporal,width of interhemispheric fissure (r=0.20,0.20;P<0.01),negatively correlation with the depth of corpus callosum (r-=-0.17;.P<0.01);social withdrawal had significantly positively correlation with the transverse diameter of third ventricle, largest width of lateral ventricle body (r=0.19,0.15;P<0.01),and negatively correlation with width of right head of caudate nucleus(r=-0.25;P<0.01);hyperactivity had significantly positively correlation with the transverse diameter of third ventricle (r=0.17;P<0.01),negatively correlation with width of left and right horn of temporal, width of left and right head of caudate nucleus and the depth of corpus callosum(r=-0.23,-0.23,-0.19,-0.15;P<0.01); the aggression behavior had significantly correlation with the transverse diameter of third ventricle (r=0.21;P<0.01), and negatively correlation with distance from lateral wall of third ventricle to right surface of insulam, width of left head of caudate nucleus and the depth of corpus callosum (r=-0.19,-0.19,-0.26;P<0.01).Conclusion1.The SNPrs821597polymorphism in DISCI gene have significant association with childhood schizophrenia.2.The gene polymorphism of rs821597in DISCI of childhood schizophrenia was significantly correlated with the brain structure:the AA genotype carriers in patients had significantly larger brain structure, and narrower width of width of left head of caudate nucleus.3.The A allele of DISCI SNPrs821597carriers in childhood schizophrenia have larger ventricular and smaller left head of caudate nucleus.4.The A allele of DISCI SNPrs821597carriers in childhood schizophrenia have worse social competencess, have significantly more hyperactivity and social withdrawl.5.The decline social competence and increase behabior problem in childhood schizophrenia have significant association with ventricular enlargement and left head of caudate nucleus narrowed. |
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