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)

A test for graphethesia and the face-hand test were performed on 84 schizophrenic inpatients: 8% of the acute-subacute group vs. 49% of the subchronic-chronic group were abnormal (p less than 0.001). Abnormalities tended to be more pronounced on the right hand, consistent with other recent lateralization findings suggesting that schizophrenia involves the left cerebral hemisphere. Those patients with positive findings had been psychotic longer and were more likely to have been referred to a psychiatrist prior to age 17. The possibility of drug-related symptoms remains a confounding issue. No differences between those who tested positive and negative were found for family history of schizophrenia, history of childhood CNS infection or trauma, premorbid asociality, CSF, EEG, or computerized axial tomography scan findings.
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PMID:Neurological abnormalities in schizophrenic patients. 737 15

Language comprehension, measured by the Luria-Nebraska Relational Concepts Factor Scale, was evaluated twice in 15 male DSM-III-R schizophrenic patients during a controlled double-blind haloperidol maintenance (without anticholinergics) and placebo replacement protocol. Fifteen male normal controls were tested once. Patients and controls were matched on age and education. Language comprehension was significantly reduced in patients under both pharmacologic conditions, as compared with controls. Patients' comprehension accuracy did not differ significantly between neuroleptic-treatment and placebo replacement conditions. Patients' comprehension accuracy was independent of positive symptoms, anxiety-depression, measures of clinical course, and CSF and plasma monoamines. Comprehension accuracy was also not associated with patients' educational level or WAIS-R measures of their intellectual and short-term memory functioning. Patients' comprehension performance was significantly associated only with the negative symptom anhedonia-asociality during haloperidol maintenance. Thus, language comprehension in schizophrenic patients was independent of changes in pharmacologic treatment and the positive symptoms of psychosis. Results suggest language comprehension may represent a stable or trait characteristic in schizophrenia.
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PMID:Language comprehension in schizophrenia: trait or state indicator? 749 22

We followed up a sample of psychiatric patients (diagnoses predominantly schizophrenia and depression) who had participated in in-patient studies of their CSF over the past 15 years. The status of 73 former patients was confirmed, of whom 12 had died. Seven of these patients died at age < or = 40, largely of suicide, homicide, or accidental causes. These seven patients had significantly lower CSF 5-HIAA and HVA than living control patients. There were significant direct correlations between age at death and both CSF 5-HIAA and HVA in the deceased patients. The results offer support for CSF monoamine metabolites relating to early death in a diagnostically diverse sample of psychiatric patients.
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PMID:An association between low levels of 5-HIAA and HVA in cerebrospinal fluid and early mortality in a diagnostically mixed psychiatric sample. 750 65

Schizophrenia is associated with multiple cognitive deficits which in turn may be related to abnormal dopamine (DA) function. To examine possible associations between cognitive dysfunction and central DA activity in schizophrenia, neuropsychological measures (visuospatial and verbal recall; performance on the Wisconsin Card Sort Test (WCST); visuospatial perception) were examined in 17 drug-free male schizophrenic patients and related to cerebrospinal fluid concentrations of the metabolites of dopamine (homovanillic acid (HVA)), serotonin, and norepinephrine. CSF HVA concentrations were correlated with the ability to recall visuospatial information, with attention to verbal tasks, and with WCST performance (low CSF HVA concentrations predicting poor performance on these tests) but not with the ability to recall verbally presented material and visuospatial perception. These data are consistent with earlier results suggesting that (cortical) DA function is associated with recall and retrieval of visuospatial information and with WCST performance.
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PMID:Neuropsychological correlates of central monoamine function in chronic schizophrenia: relationship between CSF metabolites and cognitive function. 751 87

Neurotensin (NT), a peptide which colocalizes with dopamine in some midbrain and hypothalamic neurons, has been speculated to play a role in schizophrenic illness and in the action of antipsychotic drugs. Previous work suggested a bimodal distribution of NT in patients with schizophrenia, with a subgroup having low drug-free NT concentrations which normalize with neuroleptic treatment. We studied 15 schizophrenic patients with CSF samples collected both off and on neuroleptic medication, 12 with only drug-free (DF) samples, and 10 controls. There was no significant difference in CSF NT concentrations between patients and controls, or between patients off and on medication. However, 7 patients with DFNT CSF concentrations below the patient mean showed an increase with neuroleptic treatment. Moreover, NT was significantly lower for women. Significant correlations with NT concentrations in CSF were found with deficit symptoms in patients, and with the age of the CSF sample for all subjects. There was no correlation between CSF NT concentrations and patient age, duration of illness, or levels of amine metabolites (MHPG, 5HIAA, HVA).
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PMID:CSF concentrations of neurotensin in schizophrenia: an investigation of clinical and biochemical correlates. 751 75

The effects of clozapine on the dopamine and serotonin systems may underlie its atypical pharmacologic and clinical profile. To examine this hypothesis, we measured dopamine and serotonin plasma and cerebrospinal (CSF) metabolites and the relationship of these values to treatment response in 19 neuroleptic refractory and intolerant schizophrenic patients. Only a small change in the CSF and plasma homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) levels was found. However, the pretreatment CSF HVA/5HIAA ratio and, to a lesser extent, the CSF HVA level predicted treatment response. These results suggest that the modest relationship between HVA and 5-HIAA and treatment response supports the involvement of both neurotransmitters in the pathophysiology of schizophrenia.
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PMID:The dopamine-serotonin relationship in clozapine response. 753 Mar 78

A rapidly growing body of data suggests that dysfunction in serotonergic (5-HT) function may be involved in the pathophysiology of schizophrenia, and that pharmacologic agents for this illness have their therapeutic effects mediated through serotonergic mechanisms. The purpose of this paper is to critically review data relevant to 5-HT's role in the pathophysiology and drug treatment of schizophrenia. Pathophysiologic evidence includes the psychotomimetic effects of lysergic acid (LSD), postmortem studies, single-dose 'challenge' studies and investigations of CSF and peripheral levels of 5-HT and its metabolites. The current nomenclature, potential therapeutic effects and importance of 5-HT receptor subtype antagonism will be examined. In addition, relatively novel strategies of 5-HT uptake blockade and direct acting 5-HT agonists will be assessed. A hypothesis of cortical-subcortical imbalance with an increase in subcortical 5-HT function responsible for positive symptoms and a decrease in prefrontal 5-HT function responsible for negative symptoms is proposed. Future implications of these data are discussed.
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PMID:Serotonin, schizophrenia and antipsychotic drug action. 753 88

The DRD4 dopamine receptor is thus far unique among neurotransmitter receptors in having a highly polymorphic gene structure that has been reported to produce altered receptor functioning. These allelic variations are caused by a 48-bp segment in exon III of the coding region which may be repeated from 2-10 times. Varying the numbers of repeated segments changes the length, structure, and, possibly, the functional efficiency of the receptor, which makes this gene an intriguing candidate for variations in dopamine-related behaviors, such as alcoholism and drug abuse. Thus far, these DRD4 alleles have been investigated for association with schizophrenia, bipolar disorder, Parkinson's disease, and chronic alcoholism, and all have been largely negative for a direct association. We evaluated the DRD4 genotype in 226 Finish adult males, 113 of whom were alcoholics, many of the early onset type with features of impulsivity and antisocial traits. Genotype frequencies were compared to 113 Finnish controls who were free of alcohol abuse, substance abuse, and major mental illness. In 70 alcoholics and 20 controls, we measured CSF homovanillic acid (HVA), the major metabolite of dopamine, and 5-hydroxyindoleacetic acid (5-HIAA). No association was found between a particular DRD4 dopamine receptor allele and alcoholism. CSF concentrations of the monoamine metabolites showed no significant difference among the DRD4 genotypes. This study of the DRD4 dopamine receptor in alcoholics is the first to be conducted in a clinically and ethnically homogeneous population and to relate the DRD4 genotype to CSF monoamine concentrations. The results indicate that there is no association of the DRD4 receptor with alcoholism.
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PMID:DRD4 dopamine receptor genotype and CSF monoamine metabolites in Finnish alcoholics and controls. 757 71

HPLC and gas chromatography-mass spectrometry analyses of 18 amino acids, N-acetylaspartate, N-acetylaspartylglutamate, and 5-hydroxyindoleacetic acid, derived from serotonin, and homovanillic acid, derived from dopamine, were performed in CSF collected from a group of patients with schizophrenia who either had been drug free for at least 1 year (n = 5) or were drug naive for psychotropic drugs (n = 21) and in 15 control subjects. Significant differences were found only for taurine (15% lower in the patients) and isoleucine (7% higher). A number of unidentified substances were detected, one of which proved to be markedly reduced (16%) among the schizophrenic patients. Liquid chromatography-mass spectrometry with continuous flow-fast atom bombardment interface allowed us to identify this substance as gamma-glutamylglutamine. The decreased level of gamma-glutamylglutamine may reflect a deficiency in the gamma-glutamyltransferase system, a system probably involved in glutamate uptake, or a deficiency in glutamine, an important precursor of releasable glutamate. Although glutamate was nonsignificantly reduced in the patients, it was one of the five substances (including gamma-glutamylglutamine) that were necessary for the best discrimination between the schizophrenic patients and the controls. These findings support the notion that the glutamatergic system is affected in schizophrenic disorders. In addition, they underscore the need to apply rigid bioanalytical techniques and use drug-naive patients to gain in-depth information on the pathophysiology of brain disorders such as schizophrenia.
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PMID:gamma-Glutamylglutamine and taurine concentrations are decreased in the cerebrospinal fluid of drug-naive patients with schizophrenic disorders. 759 63

Cerebrospinal fluid levels of phenylacetic acid (CSF PAA) were obtained from normal controls and from drug-free psychiatric inpatients (schizophrenia, major depression, mania, and schizoaffective disorder). Post-treatment CSF PAA levels were obtained from 16 patients after 4 weeks of neuroleptic treatment. Phenylacetic acid levels were higher in women and were significantly correlated with age. There were no differences in CSF PAA levels between the various diagnostic groups and no difference between the paranoid and the nonparanoid subtypes of schizophrenia. CSF PAA was significantly correlated with several measures of psychopathology, especially the Brief Psychiatric Rating Scale hostility/suspiciousness factor. Neuroleptic treatment did not result in significant PAA changes. These findings are discussed in light of the amphetamine-like role ascribed to phenylethylamine, the precursor of PAA.
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PMID:Cerebrospinal fluid levels of phenylacetic acid in mental illness: behavioral associations and response to neuroleptic treatment. 763 84


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