Study On Relationship Of Childhood Schizophrenia And Abnomaly Neurodevelopment

PartⅠStudy on the polymorphisms of neurotrophic factor genein childhood schizophreniaObjectiveThe primary purpose of this study was to investigate the relationshipbetween C270T polymorphisms of brain-derived neurotrophic factor(BDNF) gene and childhood schizophrenia as well as their clinicalsymptom, between neurotrophin-3 (NT-3) gene and childhoodschizophrenia as well as their clinical symptom in childhoodschizophrenia.MethodWith the method of Case-control study. The C270T polymorphismsof BDNF gene and Gly/Glu polymorphisms of NT-3 gene weregenotyped in 218 childhood schizophrenia and in 210 normal comparisonsubjects with polymerase chain reaction (PCR) methods and restrictionfragment length Polymorphism (RFLP) typing. The patients wereassigned into negative and positive schizophrenia through definition andvalidation criterion of Negative and Positive schizophrenia, and theirsymptoms were evaluated with Positive and Negative Syndrome Scale(PANSS). Compare the difference on the frequency of genotype and allele of BDNF and NT-3 gene between the childhood schizophrenia andcomparison subjects. Compare the difference on PANSS core among thepatients of different genotype.Results1.Analysis on C270T polymorphisms of BDNF gene(1)The frequency of the C/T and T/T genotype were significantlyhigh in Childhood schizophrenia (29.8％and 2.8％) compared with thecontrols (5.7％and 0, X~2=49.89, P＜0.01), after combining C/T with T/T,OR=7.97, 95％Cl=4.17～15.23. The frequency of T allele wassignificantly high in Childhood schizophrenia (17.7％) compared with thecontrols (2.9％). (2)The frequency of the C/T and T/T genotype weresignificantly high in Negative patients (46.0％and 4.8％) compared withthe Positive patients (28.6％and 1.9％, X~2=7.124, P＜0.05). Aftercombining C/T with T/T, OR=2.355, 95％Cl=1.235～4.490. Thefrequency of T allele was significantly high in Negative patients (27.8％)compared with the Positive patients (16.2％). (3)Both the patients withC/T and T/T genotype had significantly higher negative symptom scorethan C/C genotype. The patients with T/T genotype had significantlyhigher total score of PANSS than C/T genotype.2.Analysis on Gly/Glu polymorphisms of NT-3 gene(1)The frequency of the Gly/Gly, Gly/Glu and Glu/Glu genotype andGly allele were respectively 75.2％, 22.0％, 2.8％and 86.24％in Childhood schizophrenia. The frequency in comparison subjects wererespectively 64.3％, 33.3％, 2.4％,and 81.0％, The frequency of theGly/Gly genotype and Gly allele were significantly high in Childhoodschizophrenia compared with the controls (X~2=6.858, 4.370, P=0.032).(2)The frequency of the Gly/Gly, Gly/Glu and Glu/Glu genotype and Glyallele were respectively 71.43％, 25.40％, 3.17％and 84.13％in Negativepatients. The frequency in Positive patients were respectively 76.19％,20.95％, 2.96％and 86.67％, there were significance difference betweenPositive and Negative patients in the frequency of the genotype and allele(X~2=0.477, 0.415; P＞0.05). (3)There was no significance differenceamong the patients with distinct genotypes in the sub score and total scoreof the PANSS.Conclusions1.There exist genetically differences on BDNF gene C270T locusbetween patients of Childhood schizophrenia and normal comparisonsubjects. The difference might to be the pathogenic factors of Childhoodschizophrenia.2.There exist genetically differences on NT-3 gene between patientsof Childhood schizophrenia and normal comparison subjects. Thedifference might to be the pathogenic factors of Childhood schizophrenia.3.The C270T polymorphisms of the BDNF gene might not onlyinvolve in the onset of childhood schizophrenia but also have relation to negative symptom.PartⅡStudy on Minor physical anomalies and the relationshipbetween them and the polymorphisms of neurotrophic factorgene in childhood schizophreniaObjectiveTo investigate minor physical anomalies (MPAs) in childhoodschizophrenia and explore the relationship between MPAs and thepolymorphism of brain-derived neurotrophic factor gene as well asneurotrophin-3 gene.MethodsWith the method of Case-control study. One hundred sixty eightchildhood schizophrenia and 170 normal comparison subjects wereexamined for minor physical anomalies on the Waldrop scale (WS). Thesymptoms were evaluated with Positive and Negative Syndrome Scale(PANSS). Compare the difference on the WS score between thechildhood schizophrenia and comparison subjects. The risk factors onMPAs were chose with multivariabl Logitic Regression analysis. Compare the difference on WS score among different genotype of BDNFgene and among different NT-3 gene.Results1.Analysis on MPAs in childhood schizophrenia(1)Childhood schizophrenia had significantly higher rates thancomparison subjects on abnormal head circumference, fused eyebrows,telecanthus, Facial asymmetry, malformed ears, low-seatedears,.high/steepled palate, curved fifth finger, abnormal palmar crease.With multivariabl Logitic Regression analysis, these items showed thatOdds ratios were from 1.97 to 5.33..The two-group discriminant analysisdistinguishes well the childhood schizophrenic patients from the controlswith the nine predictive variables. The variables with significantcontribution to prediction of the patient-control status are abnormal headcircumference, fused eyebrows, telecanthus, Facial asymmetry,malformed ears,.high/steepled palate, curved fifth finger, low-seated earsand abnormal palmar crease. The model overall correct classification is76.0％, predicting better the controls than the schizophrenia (77.6％vs.74.4％). (2)Childhood schizophrenia had significantly higher level theWS score than comparison subjects in the global head, eye, ear, mouth,hand and the total anomalies score. (3)Negative patients had significantlyhigher level the WS score than positive patients in the global head, mouth,hand and the total anomalies score. Negative symptom was significantly positively correlated with total score of WS.2.Analysis on relationship between MPAs and the polymorphisms ofneurotrophic factors gene in childhood schizophrenia(1)relationship between MPAs and the C270T polymorphisms ofbrain-derived neurotrophic factor gene: The patients with C/T genotypehad significantly higher sub score on hands and total score of WS thanC/C genotype. There were no significantly difference on the sub score onhead, eyes, ears, mouth and feet among the patients with C/C, C/T andT/T genotype. (2) relationship between MPAs and the Gly/glupolymorphisms of neurotrophin-3 gene: The patients with Glu/Glugenotype had significantly higher sub score of WS on head than patientswith Gly/Gly and Gly/Glu genotype.Conclusions1.Childhood schizophrenia had significantly higher rate and valuesfor minor physical anomalies, especially in the craniofacial complex andhand. These results confirm that MPAs may be the trait marker ofchildhood schizophrenic patients.2.Negative patients had severe MPAs than positive patients inChildhood schizophrenia, MPAs had significant relation to negativesymptom. These results indicate that negative symptom has closerrelation to neurodevelopment in childhood schizophrenia.3.The C270T polymorphism of BDNF gene had significant relation to MPAs and negative symptom in childhood schizophrenia. Theseresults indicate that BDNF influences anomaly neurodevelopment inthese same subjects.4.The Gly/Glu polymorphism of NT-3 gene had relations with MPAsin childhood schizophrenia. These results indicate that NT-3 mayinfluence anomaly neurodevelopment in these same subjects.PartⅢStudy on ventricular enlargement and the relationshipbetween it and the polymorphisms of neurotrophic factor gene aswell as Minor physical anomalies in childhood schizophreniaObjectiveTo investigate ventricular enlargement in childhood schizophreniaand explore the relationship between it and minor physical anomalies(MPAs) as well as the polymorphism of neurotrophic factor gene.MethodsWith the method of Case-control study. One hundred sixty eightchildhood schizophrenia and 170 normal comparison subjects wereexamined for morphological abnormalities of brain. It was evaluated with ventricular-brain value by using cerebral computed tomography (CT)examination. Ventricular -brain value consists of Huckman's value,extend of third ventricle, index of ventricle, index of lateral ventricle body,index of extend of lateral ventricle and index of anterior angle of ventricle.The symptoms were evaluated with Positive and Negative SyndromeScale (PANSS). Compare the difference on the ventricular-brain valuebetween the childhood schizophrenia and comparison subjects. Therelationship between WS score and ventricular-brain value was analyzed.Compare the difference on ventricular-brain value among differentgenotype of BDNF gene and among different NT-3 gene.Results1.Analysis on ventricular enlargement in childhood schizophrenia(1)The patients had significantly higher Huckman's value and extendof third ventricle and lower index of ventricle and index of anterior anglethan normal comparison subjects. (2)Negative patients had significantlyhigher Huckman's value and extend of third ventricle and lower index ofventricle and index of anterior angle than positive patients. (3)Negativesymptom were significantly positively correlated with Huckman's valueand extend of third ventricle and negatively correlated with index ofventricle and index of anterior angle.2.Analysis on the relationship between minor physical anomaliesand ventricular enlargement in childhood schizophrenia. (1)The distinct MPAs patients (WS score≥4) had significantlyhigher Huckman's value and extend of third ventricle and lower index ofanterior angle of ventricle than inconspicuous MPAs patients (WS score≤3). (2)Tctal score of WS were significantly positively correlated withHuckman's value and extend of third ventricle and negatively correlatedwith index of anterior angle.3.Analysis on relationship between the polymorphisms ofneurotrophic factors gene and ventricular enlargement in childhoodschizophrenia.(1)relationship between ventricular enlargement and the C270Tpolymorphisms of brain-derived neurotrophic factor gene: The patientswith C/T genotype had significantly higher Huckman's value than C/Cgenotype. There were no significantly difference on extend of thirdventricle, index of ventricle, index of lateral ventricle body, index ofextend of lateral ventricle and index of anterior angle among the patientswith C/C, C/T and T/T genotype. (2)relationship between ventricularenlargement and the Gly/Glu polymorphisms of neurotrophin-3 gene:There were no significantly difference on every ventricular-brain valueamong the patients with Gly/Gly, Gly/Glu and Gly/Gly genotype.Conclusions1.Childhood schizophrenia had significantly ventricular enlargementthan comparison subjects, and the ventricular enlargement had significant relation to MPAs and negative symptom. These results indicate thatchildhood schizophrenic patients have significant anomalyneurodevelopment.2.The C270T polymorphism of BDNF gene had significant relationto ventricular enlargement and negative symptom in childhoodschizophrenia. These results indicate that BDNF influences anomalyneurodevelopment in these same subjects.3.The Gly/Glu polymorphism of NT-3 gene had not relations withventricular enlargement as well as negative symptom in childhoodschizophrenia.PartⅣstudy on cognitive function in childhoodschizophrenia and the relationship between it and minorphysical anomalies as well as ventricular enlargementObjectiveTo investigate cognitive function of childhood schizophrenia andanalyze the relationship between cognitive function and MPAs as well asventricular enlargement and explore the relationship between cognitive function and anomaly neurodevelopment.MethodsSeventy six childhood schizophrenia were examined for cognitivefunction on Chinese Wechsler intelligence scale for children(C-WISC)and Wechsler Memory Scale (WMS). Compare the difference on theC-WISC aad WMS score between the childhood schizophrenia andcomparison subjects as well as norm. Analyze the relationship betweenclinical symptom and the C-WlSC scaled core as well as the WMS scaledcore. Analyze the relationship between C-WISC and MPAs as well asventricular enlargement and between WMS core and MPAs as well asventricular enlargement.Results1.Assessing on cognitive function of childhood schizophrenia(1) Assessing on C-WISC:①Compared to norm, the percentage offull intelligence quotient (FIQ) and verbal intelligence quotient (VIQ)and performance Intelligence Quotient (PIQ) less than 79 and 89 and thepercentage of FIQ and PIQ less than 69 were significant higher than thoseof norm.②The analysis of balance between VIQ and PIQ: there arethirty nine patients (51.32％) that their VIQ minus their PIQ is equal toor more than 14, and thirty six patients (47.43％) is equal to or more than18, No patients that their PIQ minus their VIQ is equal to or more than 14. The range between VIP and PIQ varies from -11 to 58 and their average is16.49. Intelligence quotient of childhood schizophrenia is obviouslyunbalance.③Negative symptom score was significantly negativelycorrelated with the core of comprehension and vocabulary and picturecompletion and picture arrangement and total score of performance test.The score of comprehension was significantly negatively correlated withgeneral pathologic score and total score of PANSS.(2)Assessing on WMS:①Childhood schizophrenia had significantlylower score than normal comparison subjects on 100-1, recall of picture,recognizing of sight, regeneration of sight, examination of feel,understood memory, reciting number and total score of memory.②Thereare forty-one patients (53.95％) that their memory quotient (MQ) is lessthan 85, comparison subject (11.67％) seven people and norm 15.87％.Compared to subjects and norm, the percentage of anomaly MQ inpatients is significantly high.③Negative symptom score weresignificantly negatively correlated with recognizing of sight, examinationof feel and score of memory. Total score of PANSS is significantlynegatively correlated with recall of picture.2.Relationship of childhood schizophrenia cognitive function withMPAs and ventricular enlargement(1)Relationship of C-WISC with MPAs and ventricular enlargement:①The distinct MPAs patients (WS score≥4) had significantly lower score of vocabulary, block design, and total score of performance andintelligence, test than inconspicuous MPAs patients (WS score≤3).②Total score of WS is significantly negatively correlated with score ofblock design and total score of performance and intelligence test.③Huckman's value is significantly negatively correlated with score ofblock design, Score of picture arrangement is significantly positivelycorrelated with index of lateral ventricle body and index of extend oflateral ventricle.(2)Relationship of WMS with MPAs and ventricular enlargement:①The distinct MPAs patients had significantly lower score ofaccumulation, regeneration of sight, and total score of memory test thaninconspicuous MPAs patients.②Total score of WS is significantlynegatively correlated with score of accumulation and total score ofmemory test.③Huckman's value is significantly negatively correlatedwith recognizing of sight and regeneration of sight. Index of anteriorangle of wentricle is significantly positively correlated with score of1-100.Conclusions1.Childhood schizophrenia exhibited obvious cognitive impairment,the impairment was assessed after atypical antipsychotic used for 8 weeksand clinical symptom mainly improved, so cognitive impairment ofchildhood schizophrenia may be primary. But negative symptom is significantly negatively correlated with some sub and total score ofC-WISC and WMS, so the cognitive impairment may is affected bynegative symptom in a way.2. Cognitive function of childhood schizophrenia is significantlycorrelated with score of WS and ventricular enlargement, and the distinctMPAs patients had more significantly cognitive impairment thanunconspicuous MPAs patients. The results indicate that cognitiveimpairment has relation to neurodevelopment and furthermore prove thatcognitive impairment of childhood schizophrenia is primary...