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)

In a controlled study the activity of glucose-6-phosphate dehydrogenase (G-6-PD) in red and white blood cells, gamma-glutamyl transpeptidase (gamma-GT) and lysozyme in serum and white blood cells was studied in 22 drug-free schizophrenic patients and 17 healthy volunteers. The activities of the above enzymes were found to be reduced in the white cells of schizophrenics compared with controls. The differences in activity of G-6-PD in red cells and of gamma-GT and lysozyme in serum between the two groups were not revealed as significant. The observed low enzyme activities might provide a further basis for interpreting the reported functional deficiency in neutrophils of schizophrenics. Possible mechanisms in relation to biological abnormalities in schizophrenia are discussed.
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PMID:Enzyme activity of G-6-PD, gamma-GT and lysozyme in white cells of schizophrenics. 610 36

The function of maintaining concentrations (TAF) test was performed in patients with schizophrenia and hepatitis, and subjects with sleep deprivation. The results obtained are as follows: 1) Schizophrenia: It was suggested that TAF provided a reliable index of the effect and the amount of medicine as well as remissive condition. 2) Hepatitis: TAF tended to parallel the conditions of both acute and chronic hepatitis. A positive correlation was found between TAF-deviation (D) and gamma-glutamyl transpeptidase as well as lactate dehydrogenase (r = 0.682, 0.535, respectively). No significant correlation was found between TAF-level (L) and hepatic enzymes. 3) TAF-D of a 4-hour sleep group decreased significantly compared with that of a 8-hour sleep group. The lapse phenomenon of TAF curved line was observed in a 4-hour sleep group after 49 hours of sleep deprivation. It was considered that TAF was an objective index of pathological or physiological conditions.
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PMID:[Studies on the function of maintaining concentration (TAF)--evaluation of clinical symptoms (author's transl)]. 733 40

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

During the study's first stage, 284 homeless people from crisis and long-term accommodation sites were surveyed using stratified, systematic sampling. The second stage involved a survey of a convenience sample of 100 homeless people from squats and the streets. Participants completed a questionnaire, Mantoux testing was performed and blood taken for gamma-interferon assay, liver and renal function tests. The group's health status was poor, with 72% experiencing medical conditions in the preceding two years and 77% symptoms in the month prior to interview. Bronchitis, asthma and gastroenteritis were the most commonly reported conditions; productive and persistent coughing, shortness of breath and wheezing the commonest symptoms. Twenty-one per cent had Mantoux reactions 15 mm or greater, 28% a raised GGT and 19% a raised ALT. Seventy-seven per cent smoked, 74% were current drinkers, 28% had injected drugs at some time in their lives and 14% were regularly injecting drugs. Forty-four per cent had experienced mental illness, 49% of whom reported depression and 15% schizophrenia. Homeless people in Melbourne have poor health status and engage in behaviours that place their health at risk. The high number of respiratory and gastro-intestinal complaints, the high level of cigarette smoking and injecting drug use (IDU) and the proportion likely to be infected with Mycobacterium tuberculosis (MTb) are all issues with important health consequences. Participants recruited from the street had significantly poorer health and engaged in more risk behaviours than those from accommodation sites; those from the accommodated sample were more likely to be infected with Mtb.
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PMID:Health indicators and risks among people experiencing homelessness in Melbourne, 1995-1996. 965 74

For the early and correct diagnosis of the comorbidity of schizophrenia and alcoholism, a valid laboratory marker would be most helpful in clinical practice. Seventy schizophrenics admitted to a general psychiatric unit of an urban hospital located in a large industrial area in Germany prospectively underwent a detailed addiction history, the Munich Alcoholism Test (MALT) and determinations of serum gamma-glutamyltransferase (gammaGT) and carbohydrate-deficient transferrin (CDT). Cutoff levels for laboratory tests represented the 95th percentile of data obtained from 100 matched healthy controls. Using the MALT, we found evidence of concomitant alcohol consumption in 42.8% of the study patients. The sensitivities of gammaGT and CDT for detecting alcohol abuse (confirmed using DSM III-R criteria) were 70.6 and 58.8%, respectively. Our data suggest that the MALT can be used as a reliable screening test for alcohol use in schizophrenia. In neuroleptic-treated schizophrenics with pathological gammaGT, but low MALT scores, the corresponding CDT may serve as a highly specific marker to verify a concomitant alcohol abuse.
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PMID:Screening for concomitant alcohol abuse in schizophrenia: clinical significance of the Munich Alcoholism Test and laboratory tests. 1039 38

The strategy in the choice of antipsychotic agent must take into account the hepatic tolerance according to non-negligible incidence of liver disorders among psychiatric population (presence of risk factors like alcoholism, drugs of abuse intake, polymedication including potentially hepatotoxic drugs.). More than 1 000 drugs have been listed as being responsible of hepatic side effects; 16% of these agents were neuropsychiatric drugs. Antidepressive drugs (tricyclic agents or SSRI), mood stabilizing agents and neuroleptic drugs have been implicated in biological or/and clinical hepatotoxicity. For these reasons, some psychotropic agents have been withdrawn of the pharmaceutical market like alpidem or medifoxamine. Atrium*, sometimes used to correct tremor induced by neuroleptic drugs, has been withdrawn recently, as well. Isolated elevations of hepatic enzymes occur frequently with phenothiazines drugs (frequency evaluated to 20%) but also with other classes of neuroleptic agents, as well. On the contrary, clinical hepatitis have been more rarely described with neuroleptic drugs like phenothiazine agents (0,1-1%) or with haloperidol (0,002%). The definition of hepatotoxicity is based on biological parameters (elevation of alkaline phosphatase enzyme, SGPT, SGOT and GGT) or on clinical abnormalities (hepatitis, jaundice.). Clinical hepatitis could be either cytolytic or cholestatic. Clinical diagnosis and the research of its origin may include many investigations like abdominal ultrasonogram and percutaneous liver biopsy. The present article describes the cases of hepatic disorders reported with AAD (Atypical Antipsychotic Drugs), which are available in France (amisulpride, clozapine, olanzapine, risperidone). This new pharmacological class of antipsychotic drugs has showed great interest to improve negative symptoms of schizophrenia and to reduce disabling side effects like dystonia. According to the bibliographic data available, the following points and information must be clinically taken into account. Frequency of hepatic troubles: according to the bibliographic data, AAD appeared generally well tolerated in most cases. The frequency of hepatic troubles remains in general very low or rare. The cases published were observed with clozapine, olanzapine and risperidone. Nevertheless, some authors have observed higher frequency of hepatic enzymes elevation with some AAD. In an investigation comparing hepatic tolerance of clozapine (n=167) versus haloperidol (n=71), 37,3% of clozapine treated patients showed a relevant SGPT increase versus 16,6% with haloperidol. Nature of the hepatic troubles: among the clinical observations, asymptomatic biological disorders of the hepatic function are generally described but cytolytic or cholestatic hepatitis were reported, as well. Symptomatic hepatic dysfunctions were, sometimes, associated with other disorders like convulsions, pneumonia or malignant syndrome. Thus, hepatic check-up may be relevant in case of significant side-effect outcome. Delay time before the hepatic episode: hepatic injuries generally occurred within the first weeks of treatment but this delay highly varied in the literature from 1 to 8 weeks, 12 days to 5 months, 1 day to 17 months for clozapine, olanzapine and risperidone, respectively. These delay times are very similar to those observed with other psychotropic drugs. Reversibility of the hepatic troubles and rechallenge of the responsible agent: all cases were reversible after the AAD withdrawal except with one patient (39 years old) treated by clozapine (350 mg/day) who developed a fulminant and irreversible hepatitis after 8 weeks of monotherapy. In most cases, the AAD was withdrawn after the hepatic episode according to the significant risk of irreversible alteration. Nevertheless, normalization of hepatic enzymes has been described despite AAD maintenance at the same dosage or after dosage reduction. Rechallenge of clozapine after a first episode was performed for three patients, only one redeveloped a new hepatic disorder. According to different authors, special care is required if maintenance or rechallenge of the agent is indispensable after a first episode of isolated hepatic enzyme elevation (i.e resistance or intolerance to other treatments). In this case, biological and clinical supervision has to be carefully scheduled, which demands a satisfactory compliance from the patient. On the contrary, in case of clinical hepatotoxicity, rechallenge or maintenance is absolutely inadvisable. Mechanism of the hepatic troubles: precise mechanisms of the hepatotoxicity remain unclear. Contrary to phenothiazine drugs, no information is available on the respective rule of the agents and their metabolites. Hypersensitivity syndrome or eosinophilia has been reported, suggesting a possible immuno-allergic mechanism. Presence of risk factors: risk factors have been retrieved, in some observations, like high daily dosage, high plasmatic concentration, age, alcoholism, obesity or antecedent of hepatic disorders like Gilbert syndrome. Special care is advisable with these patients. As hepatotoxicity has been observed after surdosage (or suicide attempt), a hepatic check-up has to be performed in these clinical situations. Co-medication with hepatotoxic drugs may increase the risk as it has been suggested. In many observations, co-medication made difficult the incrimination of the AAD in the hepatic disorders outcome. Monotherapy has the great advantage to make easier the withdrawal of the responsible agent and its substitution. As drugs of abuse like cocaine or ecstasy are notoriously responsible of hepatotoxicity, they represent a probable factor of risk. Moreover, their detection is fundamental during the clinical investigation. Conclusion - Diagnosis of toxic hepatitis is mainly based on the chronology between agent introduction and hepatic disorder onset but other causes must be excluded. Bibliographic data analysis greatly contributes to confirm toxic hepatitis diagnosis. Nevertheless, this article emphasized the limits of bibliographic review to compare drugs towards tolerance. Most of the bibliographic data were case-reports for which it was sometimes difficult to provide absolute evidence of the responsibility of the agent. Moreover, spontaneous notification to health national administration is rarely systematic, in particular with isolated elevation of hepatic enzymes, and even more rarely published in international reviews. Nevertheless, according to the present data available in the literature, systematic and regular hepatic survey does not seem necessary in absence of risk factors. As for other side effects, which may occur more or less rapidly, great advantages may be obtained from psycho-education programs associating the patients in order to detect the first symptoms. Because little long-term hepatic follow-up comparing AAD is available, controlled studies should be carried out to precise the frequency and the risk factors (covariables) to prevent hepatitis outcome.
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PMID:[Hepatic tolerance of atypical antipsychotic drugs]. 1250 67

The prevalence of alterations of liver function tests in patients treated with a wide range of antypsychotics is unknown. The aim of this study was to analyze the effects of antipsychotics on liver function tests in a population of schizophrenic outpatients. Concentrations of AST, ALT, GGT, alkaline phosphatase, albumin, and bilirubin were determined in 54 patients fitting DSM-IV criteria of schizophrenia, and the same number of sex- and age-matched healthy subjects. Assessments included the Clinical Global Impression (CGI) and the Positive and Negative Syndrome Scale (PANSS) in addition to treatment related variables. Transaminases concentrations were slightly elevated in study patients compared to healthy controls, but without statistical significance. Alkaline phosphatase showed higher values in schizophrenic patients. Albumin and bilirubin were lower in study patients. Liver function tests abnormalities were found in about 10% of schizophrenic patients treated with antipsychotics. Treatment with depot phenotiazines induces alteration in these tests more frequently than treatment with other antipsychotics. PANSS negative subscale scores directly correlated with alkaline phosphatase and inversely correlated with albumin. A substantial number of patients in treatment with antipsychotic drugs present alterations of liver function tests. Both pharmacological and clinical factors could be related with these alterations.
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PMID:Alterations of liver function test in patients treated with antipsychotics. 1461 43

The discovery of the dipeptide gamma-glutamyltaurine (gamma-GT; glutaurine, Litoralon) in the parathyroid in 1980 and later in the brain of mammals gave rise to studies on intrinsic and synthetic taurine peptides of this type. It was suggested that gamma-glutamyltransferase (GGT; gamma-glutamyltranspeptidase) in the brain is responsible for the in vivo formation of this unusual dipeptide. gamma-GT has been prepared by both synthetic and enzymatic methods. The chemical syntheses included the use of protecting groups and coupling methods. A wide spectrum of analytical and spectroscopic methods was used to confirm the structure of the synthetic compounds and to elucidate the position of the peptide bond. Enzymatic preparation of gamma-GT from taurine takes advantage of the selective transpeptidation action of GGT on L-glutamine, glutathione, gamma-glutamyl-p-nitroanilide or other glutamine donors. Although the functional roles of gamma-GT in the brain are only poorly understood, many of its established CNS effects have been reported in the last 25 years. Its effect on emotional arousal and its anti-conflict potencies are synergistic with the anxiolytic drug diazepam. gamma-GT exhibits anti-conflict potency, which is exerted by reducing aversion or phobia and/or the anxiety levels. gamma-GT also acts as endogenous modulator in excitatory aminoacidergic neurotransmission. It is suggested that such acidic peptides through N-methyl-D-aspartic acid receptors could be part of the neurochemical substrate underlying self-stimulation of the medial prefrontal cortex. Other gamma-GT effects in neural systems include: effects on the monoamine concentration in the brain; effects on aggressive behavior in the cat; effects on thyroid hormones in the rat; amelioration of electroshock-induced amnesia; potent and long-lasting antiepileptic action (on intra-amygdaloid injection); affect the glutamatergic system in schizophrenic disorders. Roles for gamma-GT in non-neural systems have also been reported, e.g., effects on the metamorphosis of amphibians; on plasma rennin regulation; on radiation protection; on uric acid levels; on human antibody-dependent cell-mediated cytotoxicity (ADCC) and many more.
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PMID:gamma-L-glutamyltaurine. 1583 90

Brain infections as well as peripheral challenges to the immune system lead to an increased production of interleukin-1beta (IL-1beta), a cytokine involved in leukocyte-mediated breakdown of the blood-brain barrier. The effects of IL-1beta have been reported to depend on whether the route of administration is systemic or intracerebral. Using 50-day-old male rats, we compared the effects of IL-1beta on brain gamma-glutamyl transpeptidase (GGT; an enzymatic marker of brain capillary endothelium) at 2, 24 and 96 h after either an intravenous (i.v.) injection of 5 microg IL-1beta or an intracerebroventricular (i.c.v. - lateral ventricle) infusion of 50 ng IL-1beta. When the i.v. route was used, the GGT activity underwent small but significant changes; decreasing in the hippocampus 2 h after the i.v. injection, increasing 24 h later and returning to control levels at 96 h. No significant changes in the hippocampal GGT activity were observed at 2 and 24 h following the i.c.v. infusion. The GGT activity in the hypothalamus remained unchanged regardless of the route of IL-1beta administrations. Similar changes in GGT activity were revealed histochemically. The labeling was found mainly in the capillary bed, the changes being most evident in the hippocampal stratum radiatum and stratum lacunosum-moleculare. A transient increase in GGT activity at 24 h, together with a less sharp delineation of GGT-stained vessels, may reflect IL-1beta induced increased turnover of glutathione and/or oxidative stress, that may in turn, be related to altered permeability of the blood-brain barrier in some neurological and mental disorders, including schizophrenia.
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PMID:The influence of interleukin-1beta on gamma-glutamyl transpepidase activity in rat hippocampus. 1623 58

Obesity is a serious health issue for many patients with schizophrenia. There is a lack of predictors for and understanding of the development of obesity in the early phase of the illness. Therefore we investigated a set of routine biochemistry variables in blood as predictors of the development of obesity and weight gain over 5 years in an observational cohort study of patients with first-episode schizophrenia (n=59). Twelve percent of the patients were obese at baseline and 37% were obese at the 5-year follow-up. The mean body mass index (BMI) change over 5 years was a 4.1 kg/m(2) increase (4.5 SD). Obesity was predicted by baseline hemoglobin levels (odds ratio per standard deviation [OR/SD] 3.3, 95% confidence interval [CI] 1.4 to 7.5), red blood cell count (OR/SD 2.6, 95% CI 1.2 to 5.5), hematocrit (OR/SD 2.8, 95% CI 1.3 to 5.9), gamma-glutamyltransferase (OR/SD 2.8, 95% CI 1.2-6.3) and creatinine (OR/SD 3.1, 95% CI 1.2 to 8.0). After adjustment for baseline BMI, the associations were attenuated for gamma-glutamyltransferase and creatinine. Low baseline BMI was associated with a greater BMI increase. The major conclusion is that easily available routine biochemistry markers can be useful in predicting the development of obesity in first-episode schizophrenia. The mechanisms underlying the observed associations are unknown, but the predictors identified in this study could signify dehydration or insulin resistance. These observations open a new window to future research on the mechanisms underlying the development of obesity in schizophrenia.
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PMID:Biochemical risk factors for development of obesity in first-episode schizophrenia. 1984 78


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