The relationship of tardive dyskinesia to positive schizophrenia

Investigations aimed at identifying the clinical characteristics that discriminate Tardive dyskinesia (TD) from non-TD patients have yielded disparate findings. A number of studies have suggested that TD may be a feature of negative schizophrenia. In particular, the association of TD with high prevalence of "soft" neurological signs, cognitive deficits, and abnormal brain morphology on CT scan in some patients, have led several investigators to propose that negative schizophrenia may be a risk factor for TD. The neurochemical profile of TD, however, is not consistent with this hypothesis. In the following communication, we present our studies which suggest that TD is specific to and an intergral part of positive schizophrenia. The data suggest that schizophrenic patients with predominant positive symptoms may be at increased risk for the development of TD. In addition, we present evidence linking TD with left cerebral hemispheric dysfunction. By comparison, we provide evidence that negative schizophrenia is related to diencephalic damage, and discuss its relevance to negative schizophrenia and to Parkinsonism. We also provide evidence that negative schizophrenia may be a risk factor for acute drug-induced dystonia. Thus, these findings are consistent with our model that negative schizophrenia is a risk factor for Parkinsonism, whereas positive schizophrenia is related to TD. In analogy with the positive/negative dichotomy of schizophrenia, we propose that TD could be considered a "positive," where Parkinsonism a "negative" movement disorder.     

Tardive dyskinesia in schizophrenics under 60 years of age

Ninety-one schizophrenics (mean age 34 years) were examined for tardive dyskinesia (TD) during chronic neuroleptic treatment. Dyskinesia was found in 23 (25.3%). The only variable that showed an association with TD was the current doses of neuroleptics: in none of the TD patients did the dose of fluphenazine decanoate (or equivalent) exceed 45 mg/week, whereas it was higher in 23 of the 68 without TD (p less than 0.01). When these 23 "high-dose" patients were disregarded, the TD group differed significantly from the 45 dose-matched non-TD subjects in that it had more common anticholinergic drugs, more common parkinsonian symptoms, and less instances of good remission (p less than 0.05 in each case). There was no association between TD and other considered variables (drug history, age, sex, clinical characteristics, size of the lateral brain ventricles, neurological "soft" signs, cognitive impairment). The results illustrate a relationship between TD prevalence and current doses of neuroleptics and indicate that differences in doses between the groups with and without TD may obscure associations between dyskinesia and other factors.     

Brain Atrophy and Intellectual Impairment in Tardive Dyskinesia

Abstract: Fourteen chronic schizophrenic patients with tardive dyskinesia (TD) and 13 without TD were given psychological tests and CT scans. The low density rate (LDR), i.e., the ratio of the X-ray absorption (corresponding nearly to that of cerebrospinal fluid) of a brain lesion to the X-ray absorption of the whole brain, was used as an index of brain atrophy (HN-method). The LDR of the left hemisphere of the TD patients was significantly higher than that of non-TD patients in the basal nucleus and lateral ventricle, and the LDR of the right hemisphere for the TD patients was significantly higher than that of non-TD patients in the basal nucleus. The Hasegawa Dementia Rating Scale (HDRS) and Bender-Gestalt Test (BGT) for the TD patients were significantly lower than those for the non-TD patients. Our study revealed that brain atrophy was greater in TD than in non-TD patients and tended to be more pronounced in the left hemisphere, and that the degree of intellectual impairment was greater in the TD patients than in the non-TD group. The results suggest that schizophrenic brains with TD tend to be more easily damaged than those without TD, that this tendency predominates on the left side, and that intellectual impairment in TD is related to brain atrophy.     

Cognition impairment in schizophrenia patients with tardive dyskinesia: Association with plasma superoxide dismutase activity

Long-term antipsychotic treatment for schizophrenia is often associated with the emergence of tardive dyskinesia (TD), and TD presence is also accompanied by more severe cognitive impairment. Oxidative stress-induced damage may be involved in the development of TD and contribute to cognitive deficits in schizophrenia. We examined the role of oxidative stress in relation to TD and cognitive deficits in schizophrenia using plasma manganese superoxide dismutase (MnSOD) as a biomarker. We recruited 83 male chronic patients with (n = 32) and without TD (n = 51) meeting DSM-IV criteria for schizophrenia, and 58 male control subjects. We examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and MnSOD activity for all subjects. Positive and Negative Symptom Scale (PANSS) and the Abnormal Involuntary Movement Scale (AIMS) were assessed in the patients. MnSOD activity was lower in patients with TD than non-TD, and either TD or non-TD group had lower MnSOD levels than controls (all p < 0.05). Patients with TD had lower RBANS total (p < 0.05) and Visuospatial/Constructional subscale scores than non-TD patients (p < 0.01), and either TD or non-TD group scored lower than the controls on all RBANS subscales (all p < 0.001) except for the Visuospatial/Constructional index. Multiple regression analysis showed that in either TD or non-TD group, MnSOD was an independent contributor to the RBANS total score (both p < 0.05). These findings suggest that TD patients suffered oxidative stress and cognition impairment at a more severe level than non-TD patients. Oxidative stress might serve as a functionally linking node between TD development and cognition dysfunction in schizophrenia.     

Tardive dyskinesia: developmental factors

Tardive dyskinesia (TD) is an involuntary movement disorder predominantly the result of long-term neuroleptic administration. Several factors have been studied with conflicting results. In this paper, the authors compare a group of 17 TD patients with 17 non-TD controls to delineate possible etiological factors in the development of this syndrome. Factors like total neuroleptic and antiparkinsonian medication intake and organicity were not different in the groups. Only drug-free periods in the past history of TD patients were found to be statistically more significant (P less than 0.025) in these patients than in non-TD controls.     

迟发性运动障碍与血清尿酸的关系

目的：观察伴迟发性运动障碍（TD）的精神分裂症患者血清尿酸变化，探索尿酸与TD的关系。方法：采用尿酸酶法测定23例TD患者、相匹配的23例非TD患者及24例正常对照的血清尿酸水平，使用异常不自主运动量表（AIMS）评定TD的严重程度。结果：TD组血清尿酸水平显著低于非TD组及对照组（P均〈0．01），而非TD组与对照组之间血清尿酸水平无差异。TD组中AIMS评分与血清尿酸水平呈负相关（r=-0．435，P〈0．05）。结论：TD患者存在低血清尿酸水平并与TD的严重程度有关，尿酸可能参与了TD的病理生理过程。     

Cognitive impairment in tardive dyskinesia

Psychiatric patients in a prospective study on tardive dyskinesia (TD) development were psychometrically evaluated before TD onset to see whether cognitive impairment predisposes an individual to greater risk for TD. It was found that patients with TD showed more preexisting cognitive impairment than did the non-TD controls.     

COMT基因多态性与迟发性运动障碍的关联研究

目的探讨中国汉族人口中儿茶酚胺氧位甲基转移酶(COMT)基因Val108/158Met多态性与迟发性运动障碍(TD)的关系。方法以124例伴TD的精神分裂症患者(TD组)、112例不伴TD的精神分裂症患者(非TD组)及112例正常健康对照者(正常对照组)为研究对象,并采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测COMT基因多态性。结果(1)TD组与非TD组及正常对照组比较,等位基因及基因型频率均无统计学差异。(2)非TD组与正常对照组比较,非TD组的高活性G等位基因频率(0.78)显著高于正常对照组(0.70),低活性A等位基因频率(0.22)显著低于正常对照组(0.30);非TD组低活性A/A基因型频率(0.02)显著低于正常对照组(0.07)。(3)COMT基因型与TD严重程度具有显著相关性,A/A基因型患者的TD严重程度评分显著高于G/G基因型。结论本研究未发现COMT基因与TD的发生有关联。不伴TD的精神分裂症可能与COMT基因存在相关性,高活性G等位基因可能增加了不伴TD的精神分裂症的发生风险。COMT基因型与TD严重程度可能具有相关性,低活性A/A基因型患者可能较高活性G/G基因型患者表现更严重的TD。     

Neural damage in the lenticular nucleus linked with tardive dyskinesia in schizophrenia: a preliminary study using proton magnetic resonance spectroscopy

We investigated, using proton magnetic resonance spectroscopy (1H-MRS), whether the tardive dyskinesia (TD) often seen in schizophrenic patients is associated with cellular abnormalities in the basal ganglia system. The subjects in this study included schizophrenic patients with TD (TD group, n=7), schizophrenic patients without TD (non-TD group, n=7), and healthy volunteers (N group, n=7). We examined the 1H-MRS peaks of N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) in the regions of the left and right lenticular nucleus. In the left lenticular nucleus, the Cho/Cr ratio was significantly greater in the TD and non-TD groups than in the N group (Mann-Whitney U test; p<0.007 and p<0.006, respectively). Further, a significant linear trend was observed in the means of the ratio across the three groups (p<0.005); the TD group was the highest, the N group the lowest, and the non-TD group intermediate. No significant difference in the NAA/Cr ratio was found among groups. These results indicate that neural abnormalities in the basal ganglia may be linked with the neuroleptic medications and the process of the fundamental illness per se, and that more excessive damage to this neural substrate may lead to development of TD. However, as this is a preliminary study, further studies with a large number of subjects are required to verify our findings.     

Early versus late onset psychosis and tardive dyskinesia

Patients with late-onset psychosis (defined as psychosis requiring hospitalization at age 45 or more, n = 20) were compared with early-onset psychosis patients (defined as psychosis requiring hospitalization at age 25 or less, n = 56) for the prevalence of tardive dyskinesia (TD). Late-onset psychosis patients were found to have significantly more TD (p less than 0.01), which was more severe (p less than 0.05) and developed in a relatively shorter period of neuroleptic treatment (p less than 0.001), than patients with early-onset psychosis. In addition, TD patients (irrespective of early or late onset of neuroleptic treatment) were found to show a preponderance of drug-free periods (p less than 0.01) in their past neuroleptic history, more so than non-TD patients. Our findings indicate that late-onset psychosis should be considered to be a risk factor for the development of TD.     

Apolipoprotein E epsilon4 and tardive dyskinesia in a Japanese population

The findings that free radicals play a causative role in the occurrence of tardive dyskinesia (TD) and that apolipoprotein E (ApoE) 4 has decreased anti-oxidant activity suggest a potential link between TD and ApoE alleles. We, therefore, examined ApoE allelic frequencies in schizophrenic subjects with TD and non-TD. Serum samples were obtained from 333 DSM IV-diagnosed schizophrenic patients and 191 controls in Japan. The presence of TD was evaluated by research diagnostic criteria for TD. ApoE phenotypes of the serum samples were determined by polyacrylamide gel isoelectricfocusing. A total of 62 TD subjects (31 males, 31 females) were identified among all patients examined. No significant differences in ApoE allelic frequency were found between TD and non-TD groups. ApoE epsilon4 allele frequency, however, was significantly lower in the female TD group than in the male TD group. These findings do not clearly demonstrate a certain association between TD and the epsilon4 allele, but may preliminarily reveal a difference in influence of this allele on the development of TD between males and females.     

迟发性运动障碍患者血清铁调素、铁蛋白水平的研究

目的:探讨伴有迟发性运动障碍(TD)的精神分裂症患者血清铁调素(Hep)、铁蛋白(Fn)水平,以及铁代谢状况与TD的关系。方法:采用酶免疫法及化学发光法测定30例伴TD的精神分裂症患者(TD组)、41例不伴TD的精神分裂症患者(非TD组)及41名正常人(正常对照组)血清Hep、Fn水平;用异常不自主运动量表(AIMS)评估患者TD的严重程度及其与血清Hep、Fn水平的相关性。结果:TD组血清Hep水平低于非TD组及正常对照组(Z=-2.99,Z=-3.62;P均0.01),非TD组与正常对照组之间Hep水平差异无统计学意义(Z=1.22,P0.05);TD组血清Fn水平高于非TD组及正常对照组(Z=2.00,Z=2.39;P均0.05),非TD组与正常对照组之间Fn水平差异无统计学意义(Z=-0.70,P0.05)。TD组血清Hep水平与Fn水平呈负相关(r=-0.396,P0.05),AIMS评分与血清Hep及Fn水平无相关性(r=-0.052,r=0.14;P均0.05)。结论:TD患者存在铁代谢蛋白异常,铁代谢障碍可能参与了TD的病理生理过程。     

Reduced word-repetition effect in the event-related potentials of thought-disordered patients with schizophrenia

Repetition effect in event-related potentials (ERPs) was studied in 10 non-thought-disordered (non-TD) patients with schizophrenia, 8 thought-disordered (TD) patients with schizophrenia, and 10 normal control subjects while they performed a semantic categorization task with incidental word repetitions. All patients were in a stable or partially remitted stage. Although both healthy control and non-TD groups produced more positive ERPs to the repeated words than to the new words (ERP repetition effect) for 250-500 ms, the TD group did not show the ERP repetition effect. These findings suggest that the abnormal attenuation of the ERP repetition effect during semantic processing may be more prominent in schizophrenic patients with thought disorder than in those without the symptom.     

迟发性运动障碍患者血浆超氧化物歧化酶和一氧化氮及一氧化氮合酶的变化

目的 探讨血浆超氧化物歧化酶(SOD)、一氧化氮(NO)及NO合酶(NOS)的变化与抗精神病药所敛的迟发性运动障碍(TD)的关系。方法 对42例长期使用抗精神病药治疗伴有TD的男性精神分裂症患者的血浆锰SOD(MnSOD)、铜-锌SOD(CuZnSOD)、NO及NOS的活性进行测定,以59例不伴有TD男性精神分裂症患者和50例健康男性作对照组,使用异常不自主运动量表(AIMS)进行临床评估。结果 TD组MnSOD、CuZnSOD和NO分别高于非TD组(P<0.05)或正常对照组(P<0.05),TD组NOS明显低于正常对照组(P<0.05)、略高于非TD组(p<0.05)。TD组MnSOD浓度越高则TD的症状越严重、NOS则相反(P<0.01),且在TD组MnSOD与NO呈显著的负相关(p<0.05)、在非TD组或正常对照组却呈正相关(前者P<0.01)。分层后发现TD组MnSOD浓度在NO较低时显著高于非TD组(P<0.01),而在NO浓度较高时则略低于非TD组(P>0.05)。结论 抗精神病药所致的TD,可能与患者血浆SOD尤其是MnSOD活性增高以及血浆NO浓度升高密切相关,两者可能来源于不同病理过程,但均提示自由基活动异常。     

Association study of the estrogen receptor polymorphisms with tardive dyskinesia in schizophrenia

Tardive dyskinesia (TD) is an involuntary movement disorder induced by long-term antipsychotic treatments. Estrogen is suggested to modulate dopamine receptors in the central nervous system and may decrease the incidence and/or relieve the symptoms of TD. In this study, 118 schizophrenia patients with antipsychotic-induced TD and 128 sex- and age-matched non-TD schizophrenia patients were recruited. All patients were assessed by the Abnormal Involuntary Movement Scale and genotyped for the polymorphisms of estrogen receptor-alpha gene (ESR 1). There was a marginal association of the genotypes determined by PVU II between TD and non-TD patients (p = 0.057), but not of the genotypes determined by XBA I (p = 0.896). However, further studies on other polymorphisms of ESR 1 or other estrogen receptors are necessary to clarify the role of estrogen in the pathogenesis of TD.     

Defect symptoms and abnormal involuntary movement in schizophrenia

Tardive dyskinesia (TD), a possible marker of the defect state of schizophrenia, was studied along with defect symptoms in 55 neuroleptic-treated chronic schizophrenic patients. Our cross-sectional data failed to replicate earlier findings of increased defect symptoms in TD patients (n = 14), except for more severe paucity of speech content when compared with non-TD patients (n = 41). Methodological issues that may account for some of the current and previously reported findings are discussed.     

Tardive dyskinesia and pregnancy and delivery complications

Twelve children and adolescents with movements suggestive of tardive dyskinesia (TD) were compared to 49 non-TD patients while receiving neuroleptic treatment. A multiple regression analysis revealed the diagnosis of TD to be significantly associated with a history of pregnancy and delivery complications (PDCs), suggesting that these events may increase the risk of the development of treatment emergent TD. Queens Children's Psychiatric Center Queens Children's Psychiatric Center and Schneider Children's Hospital Queens Children's Psychiatric Center     

Persistent tardive dyskinesia and neuroleptic effects on glucose tolerance

The relations of persistent tardive dyskinesia (TD) to glucose tolerance and family history of type 2 diabetes mellitus (FH-NIDDM) were examined in 22 schizophrenic patients. All patients underwent a standard oral glucose tolerance test (GTT) while receiving haloperidol, and 15 patients also underwent a GTT when drug free. Fasting blood glucose (FBS) was significantly higher in the TD group than in the non-TD group in the medicated condition, but not in the drug-free state. TD and non-TD groups did not differ significantly in postload glucose levels either in the drug-free or in the medicated condition. However, relative to the drug-free state, haloperidol-treated TD patients showed decreased glucose tolerance while non-TD patients showed increased glucose tolerance. Seven (32%) of the 22 patients had an FH-NIDDM. A positive FH-NIDDM was significantly associated with the presence of TD and with higher drug-free FBS. A possible role of melatonin in mediating the TD-augmenting effects of FH-NIDDM and the neuroleptic-induced decrease in glucose tolerance has been proposed.     

No Evidence for an Association between Dopamine D2 Receptor Polymorphisms and Tardive Dyskinesia in Korean Schizophrenia Patients

Objective

Tardive dyskinesia (TD) is a long-term adverse effect of antipsychotic. Dopaminergic activity in the nigrostriatal system have been proposed to be involved in development of TD and dopamine D2 receptors (DRD2) has been regarded as a candidate gene for TD because the antipsychotics have potent antagonism DRD2. This study was aimed to find the relationship between DRD2 gene and antipsychotic-induced TD.

Methods

We evaluated whether 5 DRD2 single nucleotide polymorphisms (-141Cins>del/TaqID/NcoI/Ser311Cys/TaqIA) are associated with antipsychotic-induced TD in 263 Korean schizophrenia patients with (n=100) and without TD (n=163) who were matched for antipsychotic drug exposure and other relevant variables. Haplotype analyses were also performed.

Results

None of 5 polymorphisms were found to be significantly associated with TD and with TD severity as measured by Abnormal Involuntary Movement Scale. Overall haplotype (-141Cins>del/TaqID/NcoI/Ser311Cys/TaqIA) frequency was also not significantly different between TD and non-TD groups, although one rare haplotype (I-D1-T-G-A1) showed significantly different frequency between TD and non-TD groups (2.7% vs. 8.5%, respectively, p=0.031).

Conclusion

The present study does not support that DRD2 gene may be involved in TD in the Korean population, although further studies are warranted.     

Cognitive inhibition and thought disorder in schizophrenia

In schizophrenia, inhibitory control is reported to be disturbed and has been associated with formal thought disorder (TD). The negative priming task (NP) is used as a measure for inhibition; however, controversial results are found in the literature. The aim of this study was to evaluate cognitive inhibition in schizophrenia and TD. Additionally, the influence of the course of disease and of medication were evaluated. The NP was used to compare TD patients (n = 17) with non-TD (n = 19) and healthy controls (n = 21). Results showed similar performance among TD and non-TD patients, and controls. No influence of the course of disease or medication was found. Our results are in line with recent studies, where patients, irrespective of TD, show normal performance in the NP.