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

It is known that dysphagia in schizophrenia could result from acute or tardive dystonic reactions or parkinsonism as a result of neuroleptics. This case illustrates that dysphagia may be inherent in schizophrenia itself and not necessarily be due to neuroleptics.
 ...
PMID:Dysphagia and chronic schizophrenia: a case report. 826 16

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.
 ...
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

The clinical benefits of dopamine agonists in the management of epilepsy can be traced back over a century, whilst the introduction of neuroleptics into psychiatry practice 40 years ago witnessed the emergence of fits as a side effect of dopamine receptor blockade. Epidemiologists noticed a reciprocal relationship between the supposed dopaminergic overactivity syndrome of schizophrenia and epilepsy, which came to be regarded as a dopamine underactivity condition. Early pharmacological studies of epilepsy employed nonselective drugs, that often did not permit dopamine's antiepileptic action to be clearly dissociated from that of other monoamines. Likewise, the biochemical search for genetic abnormalities in brain dopamine function, as predeterminants of spontaneous epilepsy, proved largely inconclusive. The discovery of multiple dopamine receptor families (D1 and D2), mediating opposing influences on neuronal excitability, heralded a new era of dopamine-epilepsy research. The traditional anticonvulsant action of dopamine was attributed to D2 receptor stimulation in the forebrain, while the advent of selective D1 agonists with proconvulsant properties revealed for the first time that dopamine could also lower the seizure threshold from the midbrain. Whilst there is no immediate prospect of developing D2 agonists or D1 antagonists as clinically useful antiepileptics, there is a growing awareness that seizures might be precipitated as a consequence of treating other neurological disorders with D2 antagonists (schizophrenia) or D1 agonists (parkinsonism).
 ...
PMID:The role of dopamine in epilepsy. 878 31

Olanzapine is a potential new "atypical" antipsychotic agent. The double-blind acute phase of this study compared three dosage ranges of olanzapine (5 +/- 2.5 mg/day [Olz-L], 10 +/- 2.5 mg/day [Olz-M], 15 +/- 2.5 mg/day [Olz-H]) to a dosage range of haloperidol (15 +/- 5 mg/day [Hal]) and to placebo in the treatment of 335 patients who met the DSM-III-R criteria for schizophrenia. In overall symptomatology improvement (Brief Psychiatric Rating Scale [BPRS]-total), Olz-M, Olz-H, and Hal were significantly superior to placebo. In positive symptom improvement (BPRS-positive), Olz-M, Olz-H, and Hal were comparable and significantly superior to placebo. In negative symptom improvement (Scale for the Assessment of Negative Symptoms [SANS]-composite), Olz-L and Olz-H were significantly superior to placebo and Olz-H was also significantly superior to Hal. The most common treatment-emergent adverse events included somnolence, agitation, asthenia, and nervousness. No acute dystonia was observed with olanzapine. Treatment-emergent parkinsonism occurred with Olz-H at approximately one-third the rate of Hal, and akathisia occurred with Olz-H at approximately one-half the rate of Hal. Prolactin elevations associated with olanzapine were not significantly greater than those observed with placebo and were also significantly less than those seen with haloperidol.
 ...
PMID:Olanzapine versus placebo and haloperidol: acute phase results of the North American double-blind olanzapine trial. 2654 64

A major challenge in the clinical assessment of schizophrenia is the differentiation between depressive features, negative symptoms and neuroleptic side effects, including the adverse subjective experiences associated with this medication. The problems include the degree of symptom overlap, and the lack of precise operational definitions, particularly for negative symptoms and the putative, neuroleptic-induced deficit syndrome. The diagnostic process is further confounded by the need to discriminate between primary negative symptoms as persistent, enduring deficits, and social and emotional withdrawal secondary to positive symptoms, or related to depressive features or drug effects such as sedation and the bradykinesia component of parkinsonism. To distinguish between these elements is likely to require careful observation of patients with schizophrenia, over time, by trained raters using appropriate rating scales for depression and negative symptoms that are sensitive to change. Ratings of patients' subjective experiences regarding mood and awareness of behavioural and cognitive deficits should also be included. The associations between the subjective data and the objective ratings of depression, negative symptoms and drug side effects may help with clinical discrimination in these areas of dysfunction and with the refinement of their phenomenological descriptions.
 ...
PMID:How to distinguish between the neuroleptic-induced deficit syndrome, depression and disease-related negative symptoms in schizophrenia. 886 73

Clozapine is an 'atypical' neuroleptic that improves symptoms of many patients with schizophrenia whose illness is resistant to treatment with other neuroleptics. Unlike the 'typical neuroleptics (chlorpromazine, haloperidol), clozapine does not induce extrapyramidal symptoms such as Parkinsonism and tardive dyskinesia in humans or catalepsy in the rat. However, clozapine frequently causes epileptiform EEG changes and causes seizures in 3-5% of patients treated with this drug in therapeutic doses. Clozapine also induces dose dependent myoclonus in the partially restrained rat. In the experiments reported here, partially restrained rats were administered repeated alternate day or weekly low, fixed doses of clozapine (1 mg/kg). This dose initially caused no behavioral change. Following the third and subsequent administrations, the same dose elicited an increasing number of myoclonic seizure-like jerks reaching 140/h following the 15th injection in rats receiving the same low dose of clozapine on alternate days and 160/h following the 9th injection in animals that received the same dose once weekly. These effects are consistent with kindling, i.e. a progressive increase of brain excitability following repeated administration of a fixed subconvulsive dose of an excitatory agent. Clozapine kindled animals exhibited a significantly different pattern of early gene expression in ventral tegmental area, origin of the mesolimbic-mesocortical dopamine system and in the anterior thalamic nuclei, compared with saline treated controls subjected to exactly the same recording conditions. The evidence of central nervous system excitation with clozapine may be important to the unique therapeutic effect of this atypical antipsychotic in the treatment of symptoms, especially the deficit symptoms, of schizophrenia.
 ...
PMID:Kindling with clozapine: behavioral and molecular consequences. 898 8

This study was designed to validate an in vivo measurement of the functional sensitivity of basal ganglia neuronal circuits containing dopamine D2 receptors. We hypothesized that a D2 agonist would decrease striatopallidal neuronal activity, and hence regional cerebral blood flow (rCBF) over the axon terminals in the globus pallidus. Quantitative pallidal blood flow was measured using positron emission tomography (PET) with bolus injections of H215O and arterial sampling in six baboons before and after intravenous administration of the selective D2 agonist U91356a. We also tested whether the response to U91356a was modified by previous acute administration of various antagonists. Another baboon had serial measurements of blood flow under identical conditions, but received no dopaminergic drugs. In all animals that received U91356a, pallidal flow decreased in a dose-related manner. Global CBF had a similar response, but the decline in pallidal flow was greater in magnitude and remained significant after accounting for the global effect. A D2 antagonist, but not antagonists of D1, serotonin-2, or peripheral D2 receptors, prevented this decrease. This work demonstrates and validates an in vivo measure of the sensitivity of D2-mediated basal ganglia pathways. It also supports the hypothesis that activation of the indirect striatopallidal pathway, previously demonstrated using nonselective D2-like agonists, can be mediated specifically by D2 receptors. We speculate that the U91356a-PET technique may prove useful in detecting functional abnormalities of D2-mediated dopaminergic function in diseases such as parkinsonism, dystonia, Tourette syndrome, or schizophrenia.
 ...
PMID:PET measurement of dopamine D2 receptor-mediated changes in striatopallidal function. 909 51

Over a 6-year period, we studied 791 patients with multidrug-resistant typhoid fever, of whom 665 individuals (84%) developed neuropsychiatric manifestations. These were: acute confusional state (73%); myelitis (6%); cerebellitis (1%); parkinsonism (1%); acute psychosis (0.6%); meningo-encephalitis (0.5%); encephalitis (0.25%); sensory motor polyneuropathy, polymyositis, acute schizophrenia and bizarre neurological syndromes (0.12% each). Severe parkinsonian rigidity and meningo-encephalitis are associated with significant morbidity but very low mortality (0.5%).
 ...
PMID:Spectrum of neuropsychiatric complications in 791 cases of typhoid fever. 917 38

There is a well recognized clinical overlap between primary and secondary neuroleptic negative symptoms in schizophrenia, but their cerebral substrates are probably different. The study of these substrates could contribute to a better understanding and management of these syndromes. In the present work, the cerebral perfusion correlates, as an indirect measure of the underlying neuronal function, of negative symptoms and parkinsonism were studied with single-photon emission tomography in a group of treatment-refractory paranoid schizophrenic patients. Perfusion ratios with respect to the homolateral cerebellum were compared with a normal database. Correlation coefficients were calculated between perfusion ratios, negative symptoms and parkinsonism scores on exploratory grounds. As a group, the patients showed a bilateral, but predominantly left-sided, hypofrontality and hypotemporality, as well as an increased perfusion in right basal ganglia. Negative symptoms scores negatively correlated with prefrontal perfusion, while parkinsonism positively correlated with the activity of primary motor and sensory cortex. These findings support the existence of different cerebral substrates for primary and secondary negative symptoms in schizophrenia.
 ...
PMID:Cerebral perfusion correlates of negative symptomatology and parkinsonism in a sample of treatment-refractory schizophrenics: an exploratory 99mTc-HMPAO SPET study. 917 23

The negative symptoms of schizophrenia are often difficult to distinguish from the side effects of antipsychotic medication. In this study, we tried to clarify this issue by studying a group of patients in a clinic setting where a wide range of antipsychotic doses were being prescribed. Thirty-one patients meeting DSM-III-R criteria for schizophrenia or schizoaffective disorder were studied. Clinical ratings were carried out to assess the positive and negative symptoms of schizophrenia, parkinsonism, akathisia and tardive dyskinesia. Plasma levels were also measured for the majority of patients. Antipsychotic plasma levels were found to be highly correlated with dose. Antipsychotic dose and plasma levels were not correlated with the severity of negative symptoms, akathisia or parkinsonism. However, the severity of positive symptoms and tardive dyskinesia were positively correlated with both dose and plasma level. These findings do not support the hypothesis that higher doses of antipsychotic medication are associated with more severe negative symptoms.
 ...
PMID:Relationship between negative symptoms in chronic schizophrenia and neuroleptic dose, plasma levels and side effects. 917 29


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>