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)

Antipsychotic effects of clonidine were evaluated in one schizoaffective and seven schizophrenic patients, using a double-blind, cross-over design to compare placebo, clonidine, and standard neuroleptic drugs. Mean improvement on clonidine and neuroleptics was equal, and improvement scores on the two treatments were closely correlated for individual patients. Clonidine was selected because it blocks noradrenergic but not dopaminergic neurotransmission. Patients were selected because of co-existing psychosis and tardive dyskinesia, a movement disorder thought to be caused by the antidopaminergic properties of the neuroleptics. For all patients, dyskinesia improved when neuroleptics were discontinued during clonidine and placebo periods of the study. The data provide preliminary evidence that clonidine may be an effective alternative to neuroleptics, particularly for patients for whom the dopaminergic blocking action of the neuroleptics is undesirable. The study also prompts re-evaluation of theories of a unique role for dopamine in schizophrenia.
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PMID:Clonidine treatment of schizophrenia. Double-blind comparison to placebo and neuroleptic drugs. 613 23

The movement disorder tardive dyskinesia is a serious side effect of the long-term treatment of schizophrenia with neuroleptic drugs. Similar symptoms to those of tardive dyskinesia have been observed in Cebus apella monkeys following long-term treatment with neuroleptic drugs, and these monkeys may therefore be a useful animal model of tardive dyskinesia. Motor defects have persisted in these dyskinetic monkeys for periods of 1-6 yr after the cessation of neuroleptic treatment. We report here that in three regions of the brains of dyskinetic monkeys (substantia nigra, medial globus pallidus and subthalamic nucleus) glutamate decarboxylase activities and gamma-aminobutyric acid (GABA) levels are reduced relative to control monkeys that had been treated with neuroleptics but which showed none of the symptoms of tardive dyskinesia. These results suggest that alterations in the GABA neurone system are involved in neuroleptic drug-induced tardive dyskinesia.
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PMID:Association with persistent neuroleptic-induced dyskinesia of regional changes in brain GABA synthesis. 672 89

The literature on the putative association between cognitive dysfunction in schizophrenia and the presence of tardive dyskinesia is critically reviewed, focusing on potential artifacts and specific relationships to a particular topography of involuntary movements. These issues are exemplified via a study of cognitive function in 64 schizophrenic patients, in which impaired cognitive flexibility was identified as the primary measure distinguishing those with tardive orofacial dyskinesia. The significance of such an association with cognitive dysfunction is considered in relation to competing hypotheses of organic vulnerability to vs. state marker for this movement disorder.
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PMID:Cognitive dysfunction in schizophrenia: organic vulnerability factor or state marker for tardive dyskinesia? 810 22

The two most consistent features of the diseases caused by trinucleotide repeat expansion-neuropsychiatric symptoms and the phenomenon of genetic anticipation-may be present in forms of dementia, hereditary ataxia, Parkinsonism, bipolar affective disorder, schizophrenia and autism. To identify candidate genes for these disorders, we have screened human brain cDNA libraries for the presence of gene fragments containing polymorphic trinucleotide repeats. Here we report the cDNA cloning of CAGR1, originally detected in a retinal cDNA library. The 2743 bp cDNA contains a 1077 bp open reading frame encoding 359 amino acids. This amino acid sequence is homologous (56% amino acid identify and 81% amino acid conservation) to the Caenorhabditis elegans cell fate-determining protein mab-21. CAGR1 is expressed in several human tissues, most prominently in the cerebellum, as a message of approximately 3.0 kb. The gene was mapped to 13q13, just telomeric to D13S220. A 5'-untranslated CAG trinucleotide repeat is highly polymorphic, with repeat length ranging from six to 31 triplets and a heterozygosity of 87-88% in 684 chromosomes from several human populations. One allele from an individual with an atypical movement disorder and bipolar affective disorder type II contains 46 triplets, 15 triplets longer than any other allele detected. Though insufficient data are available to link the long repeat to this clinical phenotype, an expansion mutation of the CAGR1 repeat can be considered a candidate for the etiology of disorders with anticipation or developmental abnormalities, and particularly any such disorders linked to chromosome 13.
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PMID:cDNA cloning of a human homologue of the Caenorhabditis elegans cell fate-determining gene mab-21: expression, chromosomal localization and analysis of a highly polymorphic (CAG)n trinucleotide repeat. 873 27

Rats experimentally infected with the neurotropic RNA virus, Borna disease virus, have a hyperactive movement disorder. Because locomotor activity is modulated by the nucleus accumbens (N. Acc.) dopamine (DA) system, high-affinity DA uptake, DA D1, D2, and D3 receptor binding sites were examined in N. Acc. subregions of normal and infected rats by quantitative receptor autoradiography. The N. Acc. of infected rats had decreased mazindol and D2 and D3 radioligand binding in the core and decreased D3 radioligand binding in rostral subregions. The abnormalities observed in the N. Acc. DA system of infected rats may offer insights into the potential viral pathogenesis of psychiatric conditions with a dopaminergic substrate such as schizophrenia and affective disorders.
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PMID:A neural substrate of hyperactivity in borna disease: changes in brain dopamine receptors. 880 17

A principal components analysis was conducted upon current symptoms and signs rated in a sample of 329 essentially unselected patients with schizophrenia. Three dimensions emerged clearly and closely resembled those previously described in smaller, more selected samples. The clearly defined psychotic dimensions were related in turn to: (i) other mental state variables; (ii) physical treatments administered; (iii) movement disorder; (iv) demographic and historical features; and (v) cognitive function. The correlates of the three dimensions were very different. The clarity of separation achieved in this investigation provides strong support for the view that the three psychotic dimensions of 'poverty', 'hallucinations and delusions' and 'disorganization' are valid and may well have different underlying pathophysiologies.
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PMID:Validation of three dimensions of schizophrenic symptoms in a large unselected sample of patients. 881 1

Basic cognitive function was assessed at initial and at 5- and 10-year follow-up assessments among 41 primarily middle-aged in-patients manifesting the severest form of schizophrenia; additionally, the presence and severity of tardive dyskinesia was evaluated on each occasion. Overall, there was a modest but significant deterioration in cognitive function over the decade, particularly among older men. Longitudinally, patients with persistent tardive (orofacial) dyskinesia continued to show poorer cognitive function than those consistently without such movement disorder, though within neither group did cognitive function change over the decade. Those patients demonstrating prospectively the emergence of orofacial dyskinesia showed a marked deterioration in their cognitive function over the same time-frame within which their movement disorder emerged, but this decline did not progress further thereafter. There appears to exist some modes, progressive deterioration in cognitive function even late in the chronic phase of severe schizophrenic illness which appears to derive primarily from patients showing de novo emergence of tardive orofacial dyskinesia.
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PMID:Cognitive dysfunction in chronic schizophrenia followed prospectively over 10 years and its longitudinal relationship to the emergence of tardive dyskinesia. 881 2

Several reports have indicated that people suffering from schizophrenia show an associated abnormality in levels of certain essential fatty acids (EFAs) in blood cells. Similar abnormalities have also been noted in association with the presence of tardive dyskinesia (TD). In order to study this further, 72 patients with the diagnosis of schizophrenia or schizoaffective disorder were examined to assess the relationship between psychiatric status, movement disorder (TD) and relative levels of the n-3 and n-6 essential fatty acids in red blood cell membranes and plasma. Patients were followed up over the next 4.5 years to determine whether or not changes in clinical state showed any systematic relationship to changes in essential fatty acid levels. We hypothesised that patients with schizophrenia would show persistently lowered levels of n-6 and n-3 series essential fatty acids, compared with normal controls. We further hypothesised that this abnormality would be greater in the presence versus absence of TD and the dominance of negative rather than positive symptoms. The only consistent findings were that lower levels of linoleic acid and higher levels of dihomogamma-linolenic acid characterised the patient population compared with control subjects but there was considerable variability in patients' EFA profile.
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PMID:Schizophrenia, tardive dyskinesia and essential fatty acids. 882 55

Several studies have reported an association between schizophrenia and homozygosity for the MscI restriction site in exon 1 of the D3 dopamine receptor gene, but other studies have failed to find this association. Recent reports have suggested that the association is most salient in male patients with a family history of schizophrenia. We examined this restriction site in a group of schizophrenic patients (n = 84) and in normal controls (n = 77). Patients were subdivided according to demographic and clinical features, particular attention being paid to movement disorders. No significant difference in allelic or genotypic distribution was seen between the two groups. No association was seen between homozygosity and a positive family history, age at onset of illness, clinical subtype, negative symptom score, or movement disorder scores.
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PMID:Assessment of association of D3 dopamine receptor MscI polymorphism with schizophrenia: analysis of symptom ratings, family history, age at onset, and movement disorders. 888 61

Neuroleptics have revolutionized the treatment of schizophrenia and other psychoses since the early 1950s. Several adverse neurobiological effects are, however, associated with the long-term use of these agents. This article will review human and animal studies of these adverse effects, and also present some new data. Tardive dyskinesia (TD) is the most widely studied potentially persistent movement disorder resulting from long-term neuroleptic treatment, and several risk factors for TD development have been identified. Although drug-induced parkinsonism (DIP) usually disappears after the offending agent is withdrawn, a small portion of patients may have persistent parkinsonism. It is however, unclear if this is an aging-related effect. Persistent cognitive impairment associated with long-term use of typical neuroleptics has not been well documented. Atypical antipsychotics may produce improvement in cognitive performance in patients with chronic schizophrenia. MRI changes that are secondary to neuroleptics are possible, but have not yet been studied adequately. There is one unconfirmed report of neurofibrillary tangles associated with long-term neuroleptic use. A number of investigators have reported vacuous chewing movements, and neuropathologic changes following prolonged administration of neuroleptics in animals. We discuss the implications of the various reported adverse effects of long-term use of neuroleptics.
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PMID:Adverse neurobiological effects of long-term use of neuroleptics: human and animal studies. 979 74


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