UMLS:C0036341 - FACTA Search

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Query: UMLS:C0036341 (schizophrenia)
60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of lines of evidence converge in implicating neurodevelopmental processes in the etiology and epigenesis of schizophrenia. In this study we used a prospective, longitudinal design to examine whether adverse obstetric experiences predict schizophrenia and whether there is a deviant functional-developmental trajectory during the first 7 years of life among individuals who manifest schizophrenia as adults. The 9,236 members of the Philadelphia cohort of the National Collaborative Perinatal Project were screened for mental health service utilization in adulthood, and chart reviews were performed to establish diagnoses according to DSM-IV criteria. The risk for schizophrenia increased linearly with the number of hypoxia-associated obstetric complications but was unrelated to maternal infection during pregnancy or fetal growth retardation. Preschizophrenic cases (and their unaffected siblings who were also cohort members) manifested cognitive impairment, abnormal involuntary movements and coordination deficits, and poor social adjustment during childhood. There was no evidence of intraindividual decline in any domain, but preschizophrenic cases did show deviance on an increasing number of functional indicators with age. Together, these findings suggest that both genetic and obstetric factors participate in creating a neural diathesis to schizophrenia, the phenotypic expressions of which are age dependent, probably reflecting the maturational status of a number of interconnected brain systems.
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PMID:A prospective cohort study of neurodevelopmental processes in the genesis and epigenesis of schizophrenia. 1053 20

Spontaneous abnormal involuntary movements phenomenologically identical to neuroleptic-induced tardive dyskinesia have been described in schizophrenia for over a century. Because at present nearly all patients with schizophrenia are exposed to neuroleptic medications, information about the prevalence of spontaneous dyskinesia is obtained from accounts from the preneuroleptic era, evaluations of first-episode patients before neuroleptic treatment, and the identification and assessment of drug-naive patients in developing countries. In this report, data from 14 studies of neuroleptic-naive patients with schizophrenia are used to generate age-adjusted estimates of the prevalence of spontaneous dyskinesia. While the precision of this estimate is limited by the difficulty of obtaining large, untreated samples, available data suggest a spontaneous dyskinesia rate of approximately 4% in first-episode schizophrenic patients, 12% for patients ill several years but below age 30 years, 25% for those aged between 30 and 50 years, and 40% for those aged 60 years or older. Relative to the incidence and accrued prevalence of spontaneous dyskinesia expected during the natural history of untreated schizophrenia, the cumulative impact of treatment with new neuroleptic agents has yet to be determined.
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PMID:Prevalence of spontaneous dyskinesia in schizophrenia. 1073 25

The aim of this case report is to highlight that risperidone may cause and ameliorate tardive dyskinesia. A 16 year old white women with a 12 month history of schizophrenia, developed buccolingual masticatory tardive dyskinesia after receiving risperidone 6 mg. She had received small dosages of typical antipsychotics before and during receiving risperidone for short periods. Recommencement of risperidone with 2 mg and increasing to 6 mg resulted in improvement in tardive dyskinesia and up until now she remains free of any abnormal involuntary movements.
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PMID:Risperidone implicated in the onset of tardive dyskinesia in a young woman. 1077 99

A number of studies have shown that patients with schizophrenia smoke more than other psychiatric patients and more than the general population. Also, medicated schizophrenics who smoke present more positive symptoms of schizophrenia than non-smokers. The objective of the present study was to assess the effect of smoking on ratings of psychopathology for 30 days following discontinuation of antipsychotic medication. The subjects were 101 treatment-resistant patients with schizophrenia who had been admitted to the inpatient service of Neuroscience Research Hospital (NRH), National Institute of Mental Health, between 1982 and 1994 to undergo studies involving discontinuation of antipsychotic medication. Patients were rated independently on a daily basis on the 22-item Psychiatric Symptom Assessment Scale (PSAS), an extended version of the Brief Psychiatric Rating Scale (BPRS). At baseline, ratings for Verbal Positive, Paranoia and Loss of Function were higher in smokers (n=65) than non-smokers (n=36), but a statistically significant difference was observed only for the Verbal Positive cluster. Analysis by gender revealed that male non-smokers had the lowest psychopathology ratings at baseline. There were no differences in Anxiety/depression, Behavior Positive, Deficit Symptoms or Mannerisms (a measure for abnormal involuntary movements). Following medication discontinuation, repeated-measure analysis demonstrated a 'time' effect for all the variables studied and a 'group' (smokers vs. non-smokers) effect for Verbal Positive, Paranoia, and Loss of Function. Post-hoc comparisons at individual time points showed significantly higher ratings for smokers at week 1 for Paranoia. No differences were observed at later time points. In conclusion, at baseline, smokers had more positive symptoms and were apparently more functionally impaired than non-smokers. This difference was no longer evident after a 30 day medication discontinuation period.
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PMID:Effects of smoking during antipsychotic withdrawal in patients with chronic schizophrenia. 1112 Apr 24

The relationship between antipsychotic drugs and dyskinesias and other extrapyramidal symptoms (EPS) in schizophrenia is not simple. There is a need to study variables that may influence the occurrence of EPS in schizophrenic patients receiving drugs. The present study examined the relationship of age at onset of illness and treatment to the development of EPS in 122 middle-aged and elderly schizophrenic patients, 84 treated and 38 who had never received antipsychotic drugs. The illness had an early onset (before 45years, EOS) in 68 patients and a late onset (after 45years, LOS) in 54 patients. The patients were evaluated for dyskinesia and parkinsonism using abnormal involuntary movements scale (AIMS) and Simpson-Angus scale. The prevalence of dyskinesia and parkinsonism was similar in all the patient groups. The scores on limb-axial and severity subscales of AIMS were significantly higher in the treated than the untreated patients of the early onset group. This was not so with the late onset patients. The total parkinsonism score was higher among the treated, notably the LOS patients. The development of dyskinesia and parkinsonism in schizophrenia is possibly related to the age at onset of the illness. In late onset forms the ageing of the patient and a possible neurological abnormality related to schizophrenia might enhance the EPS-inducing effect of drugs.
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PMID:Relationship of extrapyramidal symptoms to age at onset and drug treatment in middle-aged and elderly schizophrenic patients. 1116 46

Tardive dyskinesia (TD) is a long-term adverse effect of antipsychotic drugs that are dopamine D2 receptor blockers.(1) Serotonin receptor antagonism has been proposed as a common mechanism contributing to the low extrapyramidal effects profile of atypical antipsychotic drugs.(2) We examined the association of three polymorphisms in the 5-HT2A receptor gene (HTR2A) with TD susceptibility--T102C(3) and his452tyr(4) in the coding region and A-1438G(5) in the promoter--in matched schizophrenia patients with (n = 59, SCZ-TD-Y) and without TD (n = 62, SCZ-TD-N) and normal control subjects (n = 96). The T102C and the A-1438G polymorphisms are in complete linkage disequilibrium but not his452tyr. There was a significant excess of 102C and -1438G alleles (62.7%) in the SCZ-TD-Y patients compared to SCZ-TD-N patients (41.1%) and controls (45.9%; chi(2) = 12.8, df = 2, P = 0.002; SCZ-TD-Y vs SCZ-TD-N, chi(2) = 11.4, df = 1, P = 0.0008, OR 2.41, 95% CI 1.43-3.99) and of 102CC and -1438GG genotypes (SCZ-TD-Y 42.4%, SCZ-TD-N, 16.1%, controls 20.8%, chi(2) = 13.3, df = 4, P = 0.01). The 102CC and the -1438GG genotypes were associated with significantly higher AIMS trunk dyskinesia scores (F = 3.9; df = 2, 116; P = 0.02) and more incapacitation (F = 5.0; df = 2, 115; P = 0.006). The his452tyr polymorphism showed no association with TD. These findings suggest that the 5-HT2A receptor gene is significantly associated with susceptibility to TD in patients with chronic schizophrenia. Previously reported association of the T102C and A-1438G polymorphisms with schizophrenia(6) may reflect association of a sub-group of patients with a susceptibility to abnormal involuntary movements related to antipsychotic drug exposure.
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PMID:Association between the serotonin 2A receptor gene and tardive dyskinesia in chronic schizophrenia. 1184 Mar 6

Tardive dyskinesia (TD) is a common side effect of long-term medication with typical neuroleptics. TD presents itself by abnormal involuntary movements and may lead to a potentially disabling and chronic clinical course. A vast majority of patients suffering from schizophrenia are smokers. Smoking has been reported to induce the activity of the CYP1A2 enzyme, which is an established metabolic pathway within the disposition of antipsychotics. Recently, a C-->A genetic polymorphism in the first intron of the CYP1A2 gene was reported to influence CYP1A2 activity in smokers. Subsequently, a pharmacogenetic study in 85 U.S. patients with schizophrenia (44 smokers, 41 individuals with unknown smoking status) showed the C/C genotype to be associated with higher TD severity (measured by the Abnormal Involuntary Movement Scale, AIMS) than the A/C or A/A genotype. This finding prompted us to investigate whether this effect was also present in a larger German sample of 119 patients with schizophrenia (82 smokers, 37 individuals with unknown smoking status). However, we could not replicate the reported association. The median AIMS scores did not differ between individuals with the A/A, A/C, or C/C genotypes. In an additional analysis, we compared the genotypic and allelic distribution among individuals grouped according to the criteria established by Schooler and Kane [1982: Arch Gen Psychiatry 39:486-487] (persistent TD vs. absent TD). We did not observe a differential genotypic or allelic distribution between the two diagnostic groups. Thus, our results do not support the hypothesis that the C-->A polymorphism in the CYP1A2 gene is involved in the etiology of TD in the German population.
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PMID:Lack of association between a functional polymorphism of the cytochrome P450 1A2 (CYP1A2) gene and tardive dyskinesia in schizophrenia. 1149 64

Nearly 1% of the world population suffers from schizophrenia, and neuroleptics are the major class of drugs used to treat this disorder. Neuroleptics are associated with wide variety of extrapyramidal side effects, such as akathesia, dystonia, neuroleptic malignant syndrome, Parkinson-ism and tardive dyskinesia. Despite the awareness that neuroleptics could cause extrapyramidal side effects, these drugs remain the most effective means of treating schizophrenia and Tourette's syndrome, as well as for the management of behavioral disorders in developmentally disabled individuals. Tardive dyskinesia is a complex hyperkinetic syndrome consisting of choriform, athetoid or rhythmically abnormal involuntary movements. Estimates of the prevalence rate of tardive dyskinesia in patients receiving neuroleptics range from 0.5-70%, with an average prevalence rate of 24%. Despite much research, the pathogenesis of tardive dyskinesia remains elusive. So far, various neurochemical hypotheses have been proposed for the development of tardive dyskinesia. These include dopaminergic hypersensitivity, disturbed balance between dopamine and cholinergic systems, dysfunctions of striatonigral GABAergic neurons and excitotoxicity. Similarly, different suppressive agents have been tried with limited success. Recently, the role of oxidative stress and structural abnormality in the pathophysiology of tardive dyskinesia has gained much impetus. Induction of free radicals by neuroleptic drugs leading to the oxidative stress and resultant structural abnormality could be the key factor in the pathogenesis of tardive dyskinesia. This hypothesis has been supported by numerous reports that chronic neuroleptic treatment increases free radical production and causes structural damage. More recently, the genetic vulnerability for the predisposition for the development of tardive dyskinesia, i.e., pharmacogenetic aspect of tardive dyskinesia, is also gaining impetus as a research area, and is discussed in detail in this article.
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PMID:Pathophysiology and drug therapy of tardive dyskinesia: current concepts and future perspectives. 1266 7

Free radicals may be involved in the pathogenesis of tardive dyskinesia (TD). Superoxide dismutase (SOD), a critical enzyme in the detoxification of superoxide radicals, was found to be abnormal in TD. To examine the blood SOD levels in schizophrenic patients with and without TD, and the relationships between SOD levels and tardive dyskinesia symptoms in TD patients, 45 physically healthy patients with TD who met DSM-III-R criteria for schizophrenia were compared with 45 schizophrenic patients without TD, as well as with 50 age-, sex- and smoking-matched normal controls. The severity of TD was assessed using the abnormal involuntary movement scale (AIMS). The psychopathology of patients were assessed by the Positive and Negative Syndrome Scale (PANSS). Blood SOD levels were measured by radioimmunometric assay (RIA). The results showed that the patients with TD had lower concentrations of blood SOD than those without TD, but had higher blood SOD levels than the normal controls. In the patients with TD, AIMS total score was inversely correlated with SOD levels. Our data support the view that free radicals may be involved in the pathophysiology of TD. There may exist a relationship between the free radical metabolism and the severity of dyskinesia of TD patients.
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PMID:Blood superoxide dismutase level in schizophrenic patients with tardive dyskinesia: association with dyskinetic movements. 1283 21

The objective of this retrospective study was to determine whether tardive dyskinesia (TD) represents a risk factor for supersensitive psychosis (SS) by assessing the effect of medication withdrawal on ratings of psychopathology for 30 days following discontinuation of antipsychotic medication in patients with and without TD. The subjects were 101 treatment-resistant patients with schizophrenia who had been admitted to the inpatient service of Neuroscience Research Hospital (NRH), National Institute of Mental Health, between 1982 and 1994 to undergo studies involving discontinuation of antipsychotic medication. Patients were rated independently on a daily basis on the 22-item Psychiatric Symptom Assessment Scale (PSAS), an extended version of the Brief Psychiatric Rating Scale (BPRS). The overall frequency of TD was 35.6%. Tardive dyskinesia patients were older (p < 0.0006) and had suffered from schizophrenia for a longer time (p < 0.003) than No-TD patients. Repeated measure ANOVA revealed a "time" effect for all subgroups studied. The interaction TD x time, however, was not statistically significant for any of the clusters. Within-group analysis revealed significant differences against baseline for measures of positive symptoms, negative symptoms and abnormal involuntary movements in the No-TD group 3 and 4 weeks after antipsychotic withdrawal. In the TD group, however, the changes were observed only at 4 weeks following antipsychotic discontinuation in just two of the positive symptoms cluster. Between-group analyses revealed that, at baseline, the Mannerisms cluster (abnormal involuntary movements) was significantly higher in the TD group (p < 0.05). No significant differences were observed between any of the remaining clusters at baseline or at different times following drug withdrawal. In conclusion, the relationship between SS and TD could not be confirmed in a cohort of patients with treatment-resistant schizophrenia. In the present study, patients with no TD seemed to deteriorate faster than patients with TD in terms of psychopathology and abnormal involuntary movements. It is possible that both group of patients may undergo supersensitive receptor changes, and that these changes may be more pronounced but potentially reversible in the group without TD.
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PMID:Neuroleptic withdrawal in treatment-resistant patients with schizophrenia: tardive dyskinesia is not associated with supersensitive psychosis. 1289 69

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