Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

\Drug-induced tardive dyskinesia (TD) affects approximately 20% to 30% of schizophrenic patients. Although it is usually mild, from 1% to 8% of patients may develop severe TD. Second-generation antipsychotics have demonstrated a lower risk of inducing TD. However, despite the advances brought by second-generation antipsychotics, the treatment strategies for TD remain problematic, given both the lack of an established therapeutic choice and the need for long-term use of antipsychotics in the treatment of schizophrenia. Clozapine is an atypical antipsychotic with minimal risk of inducing TD. Furthermore, it has been suggested that clozapine might actually improve the symptoms of TD. Accordingly, we evaluated the effects of clozapine on severe TD over 5 years. Seven patients meeting Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria for chronic exacerbated schizophrenia (mean age 28.5 +/- 10.2 years) and presenting severe TD, defined as Abnormal Involuntary Movements Scale score above 13, were treated with clozapine and followed up for 5 years. Extrapyramidal Symptoms Rating Scale assessment was performed in all patients at baseline, after 6 months and 3 and 5 years. Mean Extrapyramidal Symptoms Rating Scale scores decreased 83% after 3 years and 87.5% after 5 years. Mean dose for all patients was 428 +/- 269 mg/d after 5 years. Results from this open-label study suggest that clozapine may be a further option for the treatment of TD over long term.
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PMID:Maintenance treatment of severe tardive dyskinesia with clozapine: 5 years' follow-up. 1573 51

The present study investigated clozapine dosage, plasma clozapine and metabolite levels, clinical and side-effect profiles in Asian versus Caucasian patients with chronic schizophrenia who were on stable maintenance treatment. Twenty Asian patients from Singapore and 20 Caucasian patients from Australia were systematically evaluated with the following rating scales: Positive and Negative Syndrome Scale for Schizophrenia, drug attitude scale (DAI-10), drug adverse reaction profile (Liverpool University Neuroleptic Side-effect Rating Scale), extrapyramidal side-effects scales (Abnormal Involuntary Movement Scale, Simpson and Angus Scale). Cigarette and caffeine consumption were recorded and steady-state plasma clozapine and metabolites levels were measured. Although Asian patients received a significantly lower mean clozapine dose (176 mg/day) than the Caucasian group (433 mg/day, P<0.001), plasma clozapine levels were similar between the groups. As a result, Asian patients had more than twice the effective clozapine concentration to dose ratio (P<0.001). The findings remained significant even after controlling for gender, body mass index, cigarette, alcohol and caffeine use. Conversely, the plasma metabolites (desmethylclozapine and clozapine N-oxide) to clozapine ratios were higher in the Caucasian patients (P<0.01). Compared to Caucasian patients, Asian patients appeared to have a lower dosage requirement for clinical efficacy. Hence, appropriate dose adjustment should be considered in Asian patients receiving maintenance clozapine therapy in clinical practice.
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PMID:An inter-ethnic comparison study of clozapine dosage, clinical response and plasma levels. 1581 67

Assessing tardive dyskinesia (TD) has been complicated by the use of different research criteria and rating scales. We studied concordance between two commonly used scales, the Abnormal Involuntary Movement Scale (AIMS) and Extrapyramidal Symptom Rating Scale (ESRS), to study interscale concordance and criteria to define TD. Patients with schizophrenia or schizoaffective disorder (N = 374) were rated at baseline with both scales. Linear and logistic regression models explored relationships between scale ratings and mapped scores for corresponding items. TD was defined as at least mild in > or = 2 anatomical areas, or moderate or greater symptoms in > or = 1 area at baseline. Logistic regression was used to find simplified criteria for predicting AIMS-defined TD by ESRS scores. There was a strong association on corresponding item ratings. "Mild" was defined as AIMS score of 2 and ESRS 2 or 3, and "moderate or greater" as AIMS score > or = 3 and ESRS > or = 4. Using these criteria, there was 96.0% (359/374) agreement between AIMS- and ESRS-defined TD cases. The ESRS Clinical Global Impressions of severity of dyskinesia (CGI-SD) best predicted AIMS-defined TD. An ESRS CGI-SD > or = 4 (95% CI: 3.61, 4.76) was associated with > or = 95% probability of AIMS-defined TD. High concordance between the scales for dyskinesia scores was found. Findings suggest that the ESRS CGI-SD score can serve as a simplified criterion for identifying AIMS-defined TD, and may be a useful tool for future research-based TD analyses, when occurring in the context of a full movement disorder assessment.
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PMID:Abnormal Involuntary Movement Scale (AIMS) and Extrapyramidal Symptom Rating Scale (ESRS): cross-scale comparison in assessing tardive dyskinesia. 1591 63

We sought to examine stability associations between family history and variability of schizophrenia symptoms repeatedly examined during a naturalistic follow-up study. The Positive and Negative Syndrome Scale, the Insight and Treatment Attitudes Questionnaire, and the Abnormal Involuntary Movement Scale were administered to 69 patients with familial and 79 patients with sporadic schizophrenia, at hospital admission and at stabilization stage (about 16 months later). Analysis of covariance was applied to identify the association of symptom factors with familiality of schizophrenia. We found that schizophrenia patients with positive family histories had significantly higher dysphoric, activation and negative factors. However, familiality of activation and negative factors were dependent on additional variables such as age of onset (both factors), baseline ratings, insight, and side effects (negative factor). No significant association of family history with intensity of positive and autistic preoccupation factors was found. Familial schizophrenia is characterized by higher severity of dysphoric mood factors that may represent impaired emotional reactivity. It is suggested that dysphoric mood may be a useful phenotype for molecular genetic studies of schizophrenia with positive family history.
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PMID:Familiality in a five-factor model of schizophrenia psychopathology: findings from a 16-month follow-up study. 1609 2

We performed acupuncture treatment on first consultation for a female 28-year-old patient with severe axial dystonia, causing involuntary movement and abnormal posture of the neck and body, which had developed during treatment for schizophrenia. Involuntary movement involving elevation of the right shoulder began to occur in October X-1. Drugs were prescribed by her doctor, but her involuntary movement worsened and spread to the whole body. Thereafter, she began receiving acupuncture treatment at the out patient clinic for dystonia at the Kansai Medical College Hospital in July X. Involuntary movements of her neck involved repeated left lateral bending or a rigidly straight posture while sitting and standing. Her neck also showed a left lateral bend and right rotation. Her body showed a left lateral bend and right shoulder elevation. The neck problems in this case were induced by a hypertonicity of the left sternocleidomastoid (SCM), which caused the left lateral bending and right rotation of the neck. Problems in her body involved left lateral bending due to hypotonicity of the left abdominal muscle and hypotonicity of the left back muscles, which were unable to control the left lateral bending of the body. The right shoulder elevation was caused by a hypertonicity of the right trapezius and this was another of her problems. Acupuncture treatments were given using a penetrating needle method. The treatment points were left LI4 to decrease the hypertonicity of the left SCM, left ST41 to increase the hypotonicity of the left abdominal muscles, right BL60 to increase the hypotonicity of the right back muscles and right TE5 to decrease the hypertonicity of the right trapezius. At the initial stage of acupuncture treatment, the patient was not able to attend the hospital regularly enough to obtain sufficient improvement by acupuncture. In December X+1, she started to receive acupuncture treatment weekly, and the posture of the neck and body improved. In May X+3, her neck and body postures remained erect while sitting and she did not show involuntary movement. For problems of dystonia, we perform acupuncture treatment, using meridian and acupressure points selected based on the oriental medicine system, and we achieved improvement of symptoms in this case. The patient also achieved improved stability with regard to the symptoms of schizophrenia. It is suggested that acupuncture treatment has had a positive effect on tardive dystonia including axial dystonia.
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PMID:[Effect of acupuncture treatment for a patient with severe axial dystonia appearing during treatment for schizophrenia]. 1625 4

The present study comprised a naturalistic, multicentre, 5-year study of course and correlates of tardive dyskinesia (TD). One hundred and sixty-six patients treated with risperidone were included during 1995/96 and followed once a year for 5 years. Mean age at inclusion was 38 years, and mean illness duration was 12 years. Tardive dyskinesia was assessed by the Abnormal Involuntary Movement Scale, and each patient's cognitive function was tested with a comprehensive computerised test battery. At study entry, 14% had TD according to a criterion index. Fifty percent were aware of it, but few reported distress. Age and sex did not correlate with TD, but schizophrenia and bipolar diagnoses did. The presence and intensity of TD correlated with all Positive and Negative Syndrome Scale for Schizophrenia symptom dimensions except the affective factor, but not with type of medication or chlorpromazine-equivalent levels. Tardive dyskinesia patients were cognitively impaired in tests reflecting mental speed, but not in other cognitive modalities. Over the 453 patient years of exposure, five patients developed TD and 14 became free of it. Our findings support the view that TD: (i) is a dynamic phenomenon; (ii) is only partly drug-induced; (iii) has a mild course during treatment with modern neuroleptics; and (iv) appears to have some correlation with mental slowness.
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PMID:Tardive dyskinesia and antipsychotics: a 5-year longitudinal study of frequency, correlates and course. 1631 15

A possible involvement of oxidative stress in the pathophysiology of tardive dyskinesia (TD) has previously been proposed (reviewed in [Andreassen, O.A., Jorgensen, H.A., 2000. Neurotoxicity associated with neuroleptic-induced oral dyskinesias in rats. Implications for tardive dyskinesia? Progress in Neurobiology 61, 525-541.]). Long-term administration of neuroleptics alters dopaminergic turnover, which results in increased formation of reactive oxygen species (ROS). This is hypothesized to lead to TD through neuronal toxicity as a consequence of oxidative stress. In the present study, the relationship between TD and a possible functional polymorphism of the human glutathione peroxidase (GPX1) gene (an important antioxidant enzyme) was studied in 68 chronic treatment-refractory patients with schizophrenia. A proline (Pro) to leucine (Leu) substitution at codon 197 (Pro197Leu) in the GPX1 gene was genotyped. No significant difference in total Abnormal Involuntary Movements Scale (AIMS) scores was observed among patients in the three genotype groups. Moreover, no significant differences in genotype or allele frequencies were observed between subjects with and without TD. Our results suggest that the GPX1 gene polymorphism does not confer increased susceptibility to TD, although further studies are warranted before a conclusion can be drawn.
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PMID:Genetic association analysis of the glutathione peroxidase (GPX1) gene polymorphism (Pro197Leu) with tardive dyskinesia. 1641 12

Poor response to antipsychotics treatment and extrapyramidal side effects (EPS) are the most challenging problems in the treatment of schizophrenia. Several studies were investigating the impact of polymorphic cytochrome P450 2D6 gene (CYP2D6) on EPS but the results were conflicting. There are practically no clinical studies of long-term treatment of schizophrenia and CYP2D6 polymorphism. Our aim was to evaluate the influence of CYP2D6 genotype on psychopathological symptoms and the occurrence of EPS in Slovenian outpatients with schizophrenia or schizoaffective disorder in stable remission, receiving long-term maintenance antipsychotic treatment. In total 131 outpatients meeting the DSM IV criteria for schizophrenia or schizoaffective disorder and receiving maintenance therapy with haloperidol, fluphenazine, zuclopethixole or risperidone were genotyped for 14 polymorphic CYP2D6 alleles. Psychopathological symptoms were assessed with the Positive and Negative Symptom Scale for Schizophrenia (PANSS). EPS were assessed with the Simpson Angus Scale (SAS), the Barnes Akathisia Scale and the Abnormal Involuntary Movement Scale (AIMS). Six patients (4.6%) were genotyped as poor metabolizers (PMs). PMs scored significantly higher on the negative subscale for PANSS. There were no statistically significant differences between the group of PMs and the group of patients with at least one functional CYP2D6 allele in view of patient's characteristics or any of the items of the AIMS, the SAS or the Barnes Akathisia Scale. CYP2D6 genotype may not be the major factor that determines the susceptibility to antipsychotic-induced EPS in Slovenian patients in stable remission and on maintenance therapy with antipsychotics that are mainly CYP2D6 substrates. However, CYP2D6 genotype might be a factor contributing to the persistent negative symptoms of schizophrenia.
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PMID:The influence of the CYP2D6 polymorphism on psychopathological and extrapyramidal symptoms in the patients on long-term antipsychotic treatment. 1647 53

Several lines of evidence have indicated that free radicals may play a role in the pathophysiology of tardive dyskinesia (TD) (reviewed in Andreassen and Jorgensen, 2000). NAD(P)H: quinone oxidoreductase (NQO1) is an important enzyme in the human body that counteracts the oxidative stress-induced neuronal injury caused by the toxic free radicals such as dopamine-semiquinones. Taking the possible genetic predisposition to TD into account (Yassa and Ananth, 1981), the NQO1 gene is a good candidate gene that may confer increased susceptibility to TD. Based on this hypothesis, Pae et al. (2004) reported a significant association between the Pro187Ser polymorphism in the NQO1 gene and TD. In the present study, we attempted to replicate the findings of Pae et al. (2004) with the same polymorphism in 222 Japanese patients with schizophrenia. No significant difference was detected between patients with and without TD in the allelic distribution (chi2 = 0.070, d.f. = 1, p = 0.795) and in the genotypic distribution (chi2 = 0.910, d.f. = 2, p = 0.657). In addition, there was no significant difference in terms of total Abnormal Involuntary Movement Scale scores among the three genotype groups (p = 0.49). Our results suggest that the NQO1 gene polymorphism does not confer an increased risk of TD.
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PMID:No association between a functional NAD(P)H: quinone oxidoreductase gene polymorphism (Pro187Ser) and tardive dyskinesia. 1677 88

The accurate and objective measurement of abnormal, involuntary movements remains highly desirable, whether the movements are secondary to pharmacotherapy or an expression of the primary illness. In a previous study, we found that the prevalence of tardive dyskinesia in a sample of 100 subjects ranged from 28% when using the Abnormal Involuntary Movement Scale (AIMS) or the Dyskinesia Identification Scale, Condensed User Version (DISCUS) to 62% using an instrumental measurement (IM) of peripheral dyskinesia. The goal of this study was to examine the relationship between various risk factors for tardive dyskinesia as predictor variables, and the AIMS, DISCUS, and IMs of dyskinesia, tremor, and velocity of motor movement as dependent variables. The sample consisted of 100, mostly patients with schizophrenia. Poor performance on the Mini-Mental State Examination (MMSE) and increasing age were the most consistent predictors of dyskinetic and parkinsonian movements. Various predictors were associated with specific abnormal movements. Head injury was related to slower speed of motor movements and the total DISCUS score. A history of smoking was associated with less IM dyskinesia. For those with coexisting parkinsonism and dyskinesia, significant associations were found with head injury, diabetes mellitus, and an AIMS score of 2 or greater in 2 body areas. Various classes of psychotropic agents seemed to have little influence on the MMSE or the development of dyskinesia and parkinsonism. Increasing age and a lower score on the MMSE seem to be particularly helpful in gauging the risk for parkinsonian and dyskinetic movements.
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PMID:Predictors of neuroleptic-induced dyskinesia and parkinsonism: the influence of measurement methods and definitions. 1711 Aug 11


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