异丙嗪治疗迟发性运动障碍双盲对照研究

目的 :观察异丙嗪治疗迟发性运动障碍 ( TD)的疗效。方法 :3 6例住院 TD患者被随机分组接受 12周的异丙嗪或安慰剂的双盲对照治疗 ,采用肌肉注射 ( 10 0 mg/日 )与静脉点滴 ( 5 0 mg/日 )每 2周交替给药 ,结构性摄像后盲法评定量表的方法。结果 :异丙嗪组患者的不自主运动量表 ( AIMS)评分较安慰剂组有显著进步 ( P<0 .0 0 0 1) ,其显效率达 77.8%。副反应量表 ( TESS)评分两组间比较无显著性差异 ( P>0 .0 5 )。结论 :异丙嗪是一种治疗 TD有较而安全的药物 ,对于异丙嗪可能的治疗机制进行了讨论。     

经络氧疗法治疗迟发性运动障碍的临床初步观察

经络氧疗法治疗迟发性运动障碍的临床初步观察北京医科大学精神卫生研究所赵学英施万平①刘炎革２李志１汤甫琴３罗和春迟发性运动障碍（ＴａｒｄｉｖｅＤｙｓｋｉｎｅｓｉａ简称ＴＤ），系长期大量服用抗精神病药物引起的一种锥体外系毒副反应，临床特点为不自主的、有节...     

异丙治疗迟发性运动障碍双盲对照研究

目的：观察异丙嗪治疗迟发性运动障碍（ＴＤ）的疗效。方法：３６例住院ＴＤ患者被随机分组接受１３周的异丙嗪或安慰剂的双盲对照治疗，采用肌肉注射与静脉点滴每２周交替给药，结构性摄像后盲法评定量表的方法。结果：异丙嗪组患者的不自主运动量表（ＡＩＭＳ）评分较安慰剂组有显著进步，其显著效率达７７．８％，副反应量表（ＴＥＳＳ）评分两组间比较无显著性差异。结论：异丙是一种治疗ＴＤ有较而安全的药物，对于异丙嗪可能的     

迟发性运动障碍的相关问题回顾

作者参阅国内外有关迟发性运动障碍(简称TD)的相关文献,重点阐述了TD发病的危险因素、TD的发病机制以及TD的治疗进展等问题。     

伴迟发性运动障碍的慢性精神分裂症患者认知功能研究

目的:了解伴迟发性运动障碍(TD)的慢性精神分裂症患者认知功能的损害情况。方法:以82例伴TD的(TD组)、70例不伴TD的慢性精神分裂症患者(非TD组)为研究对象,两组一般情况相匹配,选用韦氏记忆测验(WMS)、威斯康星卡片分类测验(WCST)及连线测验(TMT)进行认知功能评定。结果:①两组在WMS方面比较无统计学差异。②两组在WCST方面比较,TD组错误应答数、选择错误率、错误思考时间、持续应答数及概念化水平百分数成绩均显著差于非TD组。③两组在TMT方面比较,TD组PartB耗时数显著长于非TD组,而两组PartA耗时数无显著差异。结论:伴TD的慢性精神分裂症病人存在明显的认知功能损害,且可能涉及额叶皮层。     

迟发性运动障碍与DNA甲基化之间关系的研究进展

DNA甲基化是最常见的表观遗传学修饰之一,异常的甲基化影响基因的转录和表达。有研究表明DNA甲基化可能在精神疾病的发生机制中发挥着很大的作用。本文通过综述迟发性运动障碍的研究进展及DNA甲基化可能发挥的作用,为预测TD的发生发展及临床治疗和预防提供理论依据。     

迟发性运动障碍患者血清褪黑素水平

目的对伴有迟发性运动障碍(TD的精神分裂症患者血清褪黑素(MT)水平进行对照研究,探索MT在TD病因学机制中的作用。方法伴发TD的精神分裂症患者(TD组,n=32)测定血清MT及超氧化物歧化酶(SOD)、丙二醛(MDA),以异常不自主运动量表评定TD严重程度,并与不伴TD的精神分裂症患者进行对照(非TD组,n=32)。结果①TD组血清MT水平显著低于非TD组(t=2.403,P=0.026);②TD组血清SOD水平显著低于非TD组(t=2.318,P=0.032),血清MDA水平则显著高于非TD组(t=5.011,P=0.000);③TD组患者AIMS总分与血清MT水平负相关(r=-0.396,P=0.023),与血清MDA水平正相关(r=0.431,P=0.012),血清MT水平与SOD水平正相关(r=0.361,P=0.036),与MAD水平负相关(r=-0.469,P=0.009)。结论血清低MT水平可能是精神分裂症患者TD的易患因素之一,并可能与氧化应激机制有关。     

迟发性运动障碍患者血清尿酸、催乳素水平相关性的研究

目的通过对迟发性运动障碍(TD)患者血清尿酸(UA)、催乳素(PRL)水平相关性的分析,探讨尿酸对TD保护作用的可能机制。方法测定伴TD的精神分裂症患者(TD组30例)血清尿酸、催乳素水平,并与不伴TD的精神分裂症患者(非TD组30例)进行对照;以异常不自主运动量表(AIMS)对TD临床症状进行评定。结果 TD组UA[(273±36)μmmol/L]较非TD组[(297±50)μmmol/L]显著降低(t=2.129,P=0.037);PRL[(28±7)ng/ml]较非TD组[(24±7)ng/ml]显著增高(t=-2.195,P=0.032)。TD组PRL水平与AIMS总分正相关(r=0.366,P=0.044);与血清UA水平负相关(r=-0.403,P=0.027)。结论 TD患者血清尿酸水平偏低、并与PRL水平负相关,尿酸对DA神经元可能有一定的保护作用。     

X-连锁迟发性脊椎骨骺发育不良遗传学研究进展

X-连锁迟发性脊椎骨骺发育不良(X-linked spondyloepiphyseal dysplasia tarda SEDL，OMIM 313400)是一种罕见的遗传性骨软骨发育不良性疾病，遗传方式为X连锁隐性遗传。临床特点为轻中度非匀称性矮小和早发骨关节炎。SEDL的致病基因—SEDL基因定位于Xp22、2，cDNA全长2836bp，编码含140个氨基酸残基的蛋白质，其功能尚未完全明确。51．2％的SEDL基因突变发生在外显子4和外显子5，有多种类型的突变可导致SEDL的临床表型，其中缺失突变最常见，占56．1％。SEDL基因型与临床表型之间有一定的相关性，但也存在表型异质性。     

TD的发生机制及治疗研究

迟发性运动障碍（ＴＤ）是抗精神病药物所起的严重不良反应，临床治疗比较困难，本文综述ＤＡ受体，６受体，ＧＡＢＡ受体，自由基反应等与ＴＤ发生机制的关系，及临床治疗ＴＤ的研究。     

Association between three functional polymorphisms of dopamine D2 receptor gene and tardive dyskinesia in schizophrenia

The dopamine D2 receptor (DRD2) gene is considered one of the candidate genes contributing to the development of tardive dyskinesia (TD). In the present study, we investigated the genetic association between three functional polymorphisms (Ser311Cys, ?141C Ins/Del and TaqI A) in the DRD2 gene and TD (200 patients with schizophrenia: 44 with TD and 156 without TD). No significant difference in the allelic and genotypic distribution between patients with TD and those without TD was observed. However, we found a slightly significant association between the ?141C Ins/Del polymorphism and the total Abnormal Involuntary Movement Scale (AIMS) score (P = 0.037). The significant association between the ?141C Ins/Del polymorphism and the total AIMS score did not remain after the regression analysis was taken into account (P = 0.14). Our results suggest that that three functional polymorphisms in DRD2 may not play a major role in the occurrence of TD. © 2001 Wiley‐Liss, Inc.     

5-HT2C (HTR2C) serotonin receptor gene polymorphism associated with the human personality trait of reward dependence: Interaction with dopamine D4 receptor (D4DR) and dopamine D3 receptor (D3DR) polymorphisms

We recently reported an association between the long repeat allele of the dopamine D4 exon III receptor polymorphism and a human personality dimension, novelty seeking, as measured by the tridimensional personality questionnaire (TPQ), a personality instrument designed by Cloninger to reflect heritable facets of human temperament. The D4 receptor polymorphism (D4DR) accounts for only a small percent of the variance for this trait, suggesting that additional genes influence both novelty seeking as well as the other temperaments that are inventoried by the Cloninger TPQ. In the current investigation, we examined, in the original cohort of 120 normal volunteers, two additional coding region polymorphisms, a glycine to serine substitution in the dopamine D3 receptor (D3DR) and a cysteine to serine substitution in the 5-HT_2C serotonin receptor (HTR2C). Three-way analysis of variance (TPQ score grouped by D4DR, D3DR and 5-HT_2C) demonstrated that reward dependence and persistence scores were significantly reduced by the presence of the less common 5-HT_2Cser polymorphism. The effect of the serine substitution in this X-linked serotonin receptor polymorphism on reward dependence was also observed when male and female subject groups were separately analyzed. There was also a significant interaction between the two dopamine receptor polymorphisms and the serotonin polymorphism on reward dependence. In particular, the effect of the 5-HT_2C polymorphism on reward dependence was markedly accentuated in individuals who had the long version of the D4DR exon III repeat polymorphism. When present in the same individual, the 5-HT_2C and dopamine receptor polymorphisms account for 30% of the observed variance for persistence (RD2) and 13% of the variance for reward dependence scores (RD134). However, the number of subjects with both less common D4DR and 5-HT_2C polymorphisms is small, underscoring the importance of verifying this interaction in a larger cohort. Am. J. Med. Genet. 74:65–72, 1997. © 1997 Wiley-Liss, Inc.     

Genetic contribution of tumor necrosis factor (TNF)-alpha gene promoter (-1031, -863 and -857) and TNF receptor 2 gene polymorphisms in endometriosis susceptibility

PROBLEM: Tumor necrosis factor (TNF)-alpha is a major cytokine involved in inflammatory and immune function. The aim of this study was to investigate whether polymorphisms at positions -1031, -863 and -857 in the TNF gene promoter region (TNFA) and TNF receptor type 2 gene (TNFR2) are responsible in part for genetic susceptibility to endometriosis. METHODS OF STUDY: TNFA and TNFR2 polymorphisms were determined in 123 patients with endometriosis and 165 fertile healthy women by the polymerase chain reaction (PCR) - preferential homoduplex formation assay and PCR-restriction fragment length polymorphism, respectively. RESULTS: The frequency of the TNFA-U01 haplotype was increased significantly in patients with endometriosis compared with controls (P = 0.045, OR = 1.45). The TNFA-U01 haplotype was strongly associated with HLA-B*0702. No difference was found in TNFR2 polymorphism between patients and controls. CONCLUSION: Our results indicated that TNFA promoter polymorphism was associated with susceptibility to endometriosis. However, this association was not independent of HLA-class I polymorphisms.     

Further evidence of no association between Ser9Gly polymorphism of dopamine D3 receptor gene and schizophrenia

Dopamine D3 receptor (DRD3) was demonstrated to have important implications in schizophrenia, because it binds antipsychotic drugs and is abundant in the limbic system of the brain. Several groups attempted to find an association between a serine-to-glycine polymorphism at codon 9 of the DRD3 gene (Ser9Gly) and schizophrenia; however, the results were inconsistent. We conducted a case-control association study in Han Chinese schizophrenic patients from Taiwan, to examine the relationship of this serine-to-glycine polymorphism and schizophrenia. We noted no significant differences of genotype distribution, allele frequencies, or homozygosity proportion of this polymorphism between schizophrenic patients (N = 178) and controls (N = 100). When patients were divided according to sex, or presence or absence of family history, the differences were still not significant. Our study does not support the contention that the Ser9Gly polymorphism of the DRD3 gene plays a major role in schizophrenia. Am. J. Med. Genet. 74:40–43, 1997. © 1997 Wiley-Liss, Inc.     

Association of dopamine D3‐receptor gene variants with neuroleptic induced akathisia in schizophrenic patients: A generalization of Steen's study on DRD3 and tardive dyskinesia

Neuroleptic induced akathisia is a common and distressful extrapyramidal side effect of antipsychotic treatment. A significant proportion of the variability of its development has been left unexplained and has to be attributed to individual susceptibility. Since hereditary factors have been discussed in the etiology of acute akathisia (AA), part of the individual susceptibility might be of genetic origin. Moreover, AA is regarded as a forerunner of tardive dyskinesia, a drug‐induced chronic movement disorder, which may be associated with homozygosity for the Ser9Gly variant of the DRD3 gene. Considering expression studies, which demonstrated functional variants of DRD3 polymorphisms, we investigated whether homozygosity for the Ser9Gly variant of the DRD3 gene is associated with AA. Homozygosity for the Ser9Gly variant of the DRD3 gene was connected to an 88% incidence of AA as compared with a considerably lower 46.9% incidence of AA in schizophrenic patients nonhomozygous for the 2‐2 allele (exact P = 0.0223). Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:187–191, 2000. © 2000 Wiley‐Liss, Inc.     

Lack of association between TaqI A1 allele of dopamine D2 receptor gene and alcohol-use disorders in Atayal natives of Taiwan

Association studies between the A1 allele of the dopamine D2 receptor (DRD2) gene TaqI A polymorphism and alcoholism remain controversial. A recent study from Japan demonstrated that the A1 allele is associated with severe alcoholism in the Japanese population. We were interested in knowing if this association also exists in the Atayals of Taiwan, who were found to have a higher prevalence of alcohol-use disorders than the Han Chinese in Taiwan. Genotype and allele frequencies were determined in alcohol-abusing, alcohol-dependent, and nonalcoholic control Atayal natives in Taiwan. A1 allele frequencies in alcohol-dependent, alcohol-abusing, and normal control Atayals were 0.39, 0.42, and 0.39, respectively. No difference in A1 allele frequency was found among these three groups. Our data do not support the hypothesis that the A1 allele of the TaqI A polymorphism of the DRD2 gene increases susceptibility to alcohol-use disorders in the Atayals of Taiwan. © 1996 Wiley-Liss, Inc.     

Investigation of the dopamine D5 receptor gene (DRD5) in adult attention deficit hyperactivity disorder

Several lines of evidence from neuroimaging, pharmacology and genetics support the involvement of the dopaminergic system in the etiology of Attention Deficit Hyperactivity Disorder (ADHD). Previous candidate gene studies have investigated the association between a dinucleotide (CA)(n) repeat polymorphism, located 18.5 kb from the start codon of the DRD5 gene, and ADHD. Association between the 148 bp allele and ADHD has been reported in some studies, however replication of the finding has not been consistent. We tested for an association between the (CA)(n) repeat and adult ADHD in a sample comprised of 119 families with adult ADHD probands and 88 unrelated adult ADHD cases with a corresponding number of controls matched for age, ethnicity and sex. In the family sample we found a non-significant trend for association between the 148 bp allele and ADHD (Z=1.91, p=0.055). An excess of non-transmissions was detected for the 150 and 152bp alleles (Z=-2.26, p=0.023; Z=-2.20, p=0.028). Quantitative analysis performed using the Brown Attention Deficit Disorder Scale (BADDS) showed association between the 150 bp allele and lower total score (p=0.011), and lower effort (p=0.008), activation (p=0.008) and attention (p=0.01) cluster scores. We did not replicate association findings in the case-control group, likely due to the lack of statistical power of this sample. Our findings add to the literature suggesting DRD5 (CA)(n) repeat has a modest effect in modulating susceptibility to adult ADHD but further studies are required.     

Association study of schizophrenia and the dopamine D3 receptor gene locus in two independent samples

Using a case-control design, an association of schizophrenia with the dopamine D3 receptor gene (D3RG) locus was investigated. Initial analysis of pooled results from published studies revealed a significant excess of individuals homozygous for either allele among the patients. The association was next tested in two cohorts ascertained independently at Pittsburgh, Pennsylvania and at Houston, Texas. The Pittsburgh sample was comprised of patients with schizophrenia (DSM-III-R) (n = 130). The controls belonged to two groups: adults screened for the absence of substance abuse or major psychiatric illness (n = 128), and neonates (n = 160). Multivariate analysis suggested an association with allele 1 of the biallelic D3RG polymorphism in comparison with the adult, but not the neonatal, controls. The association was most marked among Caucasian patients with a family history of schizophrenia (odds ratio 13.69, confidence intervals 1.80, 104.30). Survival analysis suggested an earlier age of onset among male patients homozygous for allele 2. The Houston cohort included Caucasian patients with schizophrenia or schizoaffective disorder (DSM-III-R criteria, n = 50), and normal controls matched for gender (n = 51). In this group, no significant associations were noted among all the patients or among subgroups of patients based on family history or age of onset. Possible reasons for the discordant results are discussed. © 1996 Wiley-Liss, Inc.     

Adult attachment and gene polymorphisms of the dopamine D4 receptor and serotonin transporter (5-HTT)

Recently, the Dopamine D4 Receptor Gene (DRD4) and the Serotonin Transporter Gene (5-HTT) have been found to be candidate genes for infant attachment disorganization. The present study aimed to explore the relationship of these genes to adult attachment representations. The Adult Attachment Interview was used to assess attachment representations in 167 German adults. DNA from buccal cells was genotyped for the DRD4 VNTR Exon III and 5-HTT LPR polymorphisms with respect to the presence of the 7repeat allele and the short allele, respectively. DRD4 7repeat allele carriers were significantly more likely to be securely attached than those without 7repeat but only for subjects with unloving caregiver recollections. No association between the 5-HTT LPR polymorphism and adult attachment was found. These findings encourage further investigations to explore endophenotypical and mediating psychological processes between the DRD4 Gene and secure attachment patterns.