RESUMO
AIMS: Previous studies have supported the claim that psychological stress induces the production of reactive oxygen species. Several authors have suggested that patients with psychiatric disorders show high levels of oxidative stress markers. We examined different oxidative stress markers in patients with chronic schizophrenia. METHODS: This study included 29 patients with chronic schizophrenia and 30 healthy volunteers. The concentration of urinary biopyrrins and 8-hydroxydeoxyguanosine (8-OHdG), as measured by enzyme-linked immunosorbent assay, were normalized to the urinary concentration of creatinine. Psychiatric symptoms were assessed by the administration of the Brief Psychiatric Rating Scale (BPRS). RESULTS: The concentration of biopyrrins in patients with chronic schizophrenia was significantly higher when compared with healthy volunteers. The correlation between biopyrrin level and the duration of illness was highly significant. There were no significant differences in the levels of urinary 8-OHdG between the two groups. In schizophrenic patients, the level of urinary biopyrrins showed correlations with BPRS scores, while the level of urinary 8-OHdG did not show correlations with BPRS. CONCLUSIONS: Urinary biopyrrins are increased in patients with chronic schizophrenia while urinary 8-OHdG is not increased. These findings suggest that patients with chronic schizophrenia are under the condition of certain oxidative stresses.
Assuntos
Bilirrubina/análogos & derivados , Bilirrubina/urina , Desoxiguanosina/análogos & derivados , Estresse Oxidativo , Esquizofrenia/urina , 8-Hidroxi-2'-Desoxiguanosina , Adulto , Bilirrubina/metabolismo , Biomarcadores , Estudos de Casos e Controles , Doença Crônica , Desoxiguanosina/urina , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Nicotine has been proposed to be a cognitive enhancer, particularly in schizophrenia patients. So far, the published studies of nicotine effects on antisaccade performance in schizophrenia patients only tested participants who were deprived smokers. Thus, we aimed to test both smoking and non-smoking patients as well as healthy controls in order to extend previous findings. Moreover, we employed a paradigm using standard and delayed trials. We hypothesized that, if nicotine is a genuine cognitive enhancer, its administration would improve antisaccade performance both in smoking and non-smoking participants. A total of 22 patients with schizophrenia (12 smokers and 10 non-smokers) and 26 controls (14 smokers and 12 non-smokers) completed the study. The effects of a nicotine patch (14 mg for smokers, 7 mg for non-smokers) on antisaccade performance were tested in a randomized, double-blind, placebo-controlled, cross-over trial. Schizophrenia patients made significantly more antisaccade errors than controls (p = 0.03). Both patients and controls made fewer antisaccade errors in the delayed trials than in the standard trials (p < 0.0001). Nicotine significantly reduced antisaccade error rate in the standard trials, but not in the delayed trials (p = 0.02). Smoking status did not influence the nicotine effect on antisaccade error rate (p = 0.10) indicating an equal procognitive effect of nicotine in smokers and non-smokers. Overall the present findings indicate that beneficial effects of nicotine on antisaccade performance are not confined to smoking schizophrenia patients. Instead, the findings likely represent genuine nicotine-induced enhancement of cognitive performance.
Assuntos
Nicotina/administração & dosagem , Agonistas Nicotínicos/administração & dosagem , Movimentos Sacádicos/efeitos dos fármacos , Esquizofrenia/tratamento farmacológico , Fumar/psicologia , Administração Cutânea , Adolescente , Adulto , Análise de Variância , Cotinina/sangue , Estudos Cross-Over , Método Duplo-Cego , Eletroculografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Reação/efeitos dos fármacos , Esquizofrenia/sangue , Esquizofrenia/urina , Estatística como Assunto , Adulto JovemRESUMO
Early findings propose that impaired neurotransmission in the brain plays a key role in the pathophysiology of schizophrenia. Recent advances in understanding its multiple etiologies and pathogenetic mechanisms provide more speculative hypotheses focused on even broader somatic systems. Using a targeted tandem mass spectrometry (MS/MS)-based metabolomic platform, we compared metabolic signatures consisting of monoamine and amino acid neurotransmitter (NT) metabolites in plasma/urine simultaneously between first-episode neuroleptic-naïve schizophrenia patients (FENNS) and healthy controls before and after a 6-week risperidone monotherapy, which suggest that the patient NT profiles are restoring during treatment. To detect and identify potential biomarkers associated with schizophrenia and risperidone treatment, we also performed a combined ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) and 1H nuclear magnetic resonance (NMR)-based metabolomic profiling of the same samples, indicating a further deviation of the patients' global metabolic profile from that of controls. The NTs and their metabolites together with the 32 identified biomarkers underpin that metabolic pathways including NT metabolism, amino acid metabolism, glucose metabolism, lipid metabolism, energy metabolism, antioxidant defense system, bowel microflora and endocrine system are disturbed in FENNS. Among them, pregnanediol, citrate and α-ketoglutarate (α-KG) were significantly associated with symptomatology of schizophrenia after Bonferroni correction and may be useful biomarkers for monitoring therapeutic efficacy. These findings promise to yield valuable insights into the pathophysiology of schizophrenia and may advance the approach to treatment, diagnosis and disease prevention of schizophrenia and related syndromes.
Assuntos
Antipsicóticos/uso terapêutico , Risperidona/uso terapêutico , Esquizofrenia/sangue , Esquizofrenia/urina , Adolescente , Adulto , Antipsicóticos/farmacologia , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Feminino , Humanos , Análise dos Mínimos Quadrados , Masculino , Metaboloma/efeitos dos fármacos , Análise Multivariada , Risperidona/farmacologia , Esquizofrenia/tratamento farmacológico , Adulto JovemRESUMO
AIM: Change in catecholamine seems to be associated with not only effects of electroconvulsive therapy (ECT), but also adverse events associated with ECT. Our aim in this study was to investigate whether or not ECT influences the concentration of catecholamine over the long term. Patients with a major depressive episode or schizophrenia, diagnosed according to DSM-IV criteria, who were newly admitted to Juntendo University Hospital to receive ECT, were recruited. METHODS: Urine was collected during the 24 h before the first ECT treatment, during the 24 h after the first ECT treatment, during the 24 h after the final ECT treatment and during the 24 h 1 week after the final ECT treatment. Heart rate, the Hamilton Rating Scale for Depression and the Positive and Negative Syndrome Scale were assessed before and after ECT. RESULTS: Twenty-four patients were included in the final sample, which consisted of 14 patients with major depressive episodes and 10 patients with schizophrenia. Abnormal electrocardiograms were indicated in four patients with depression during the ECT operation but all recovered naturally. There were no significant differences in the levels of dopamine, adrenaline or noradrenaline the day before the first ECT, a day after the first ECT, a day after the final ECT and a week after the final ECT. CONCLUSION: These results suggest that ECT does not alter urine catecholamine levels after ECT over the long term. Further studies will be required to confirm these findings in a larger sample of patients.
Assuntos
Catecolaminas/urina , Transtorno Depressivo Maior/urina , Eletroconvulsoterapia , Esquizofrenia/urina , Idoso , Transtorno Depressivo Maior/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Esquizofrenia/terapia , Resultado do TratamentoRESUMO
A compound identified as 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA) was found in higher concentrations in urine samples of children with autism compared to age and sex appropriate controls and in an adult with recurrent diarrhea due to Clostridium difficile infections. The highest value measured in urine samples was 7500 mmol/mol creatinine, a value 300 times the median normal adult value, in a patient with acute schizophrenia during an acute psychotic episode. The psychosis remitted after treatment with oral vancomycin with a concomitant marked decrease in HPHPA. The source of this compound appears to be multiple species of anaerobic bacteria of the Clostridium genus. The significance of this compound is that it is a probable metabolite of m-tyrosine (3-hydroxyphenylalanine), a tyrosine analog which depletes brain catecholamines and causes symptoms of autism (stereotypical behavior, hyperactivity, and hyper-reactivity) in experimental animals.
Assuntos
Transtorno Autístico/urina , Trato Gastrointestinal/microbiologia , Fenilpropionatos/urina , Esquizofrenia/urina , Doença Aguda , Adolescente , Adulto , Criança , Pré-Escolar , Clostridioides difficile , Clostridium/metabolismo , Infecções por Clostridium/complicações , Infecções por Clostridium/tratamento farmacológico , Enterocolite Pseudomembranosa/microbiologia , Enterocolite Pseudomembranosa/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenilalanina/metabolismo , Esquizofrenia/complicações , Caracteres Sexuais , Vancomicina/uso terapêutico , Adulto JovemRESUMO
OBJECTIVE: Previous studies have suggested that the endogeneous psychotomimetic molecule bufotenine (N-N-dimethyl-5-idroxytryptamine) may play a role in the pathogenesis of severe mental disorders. The potential association of bufotenine with the clinical features of autism and schizophrenia is not entirely understood. In this study, we measured urinary levels of bufotenine in subjects with autistic spectrum disorder (ASD), schizophrenia and healthy comparison subjects free of psychiatric symptoms. We also sought to assess whether urine concentrations of this molecule may be associated with the clinical characteristics of psychiatric patients. DESIGN: Urine bufotenine levels were measured using a high-performance liquid chromatography-mass spectrometry (HPLC-MS) assay in young adults with severe ASD (n=15), patients with schizophrenia (n=15), and healthy control subjects (n=18). The Vineland Adaptive Behavior Scale was used to measure adaptive behaviors in ASD individuals. The Brief Psychiatric Rating Scale (BPRS) was used for patients with schizophrenia. RESULTS: Urine bufotenine levels were significantly higher in ASD subjects (3.30 +/- 0.49 microg/L, p<0.05) and patients with schizophrenia (4.39 +/- 0.43 microg/L, p<0.001) compared with controls (1.53 +/- 0.30 microg/L). Among patients with ASD, there was a significant positive correlation between urine bufotenine and hyperactivity scores on the Vineland Adaptive Behavior Scale (r=0.479, p<0.05). No other associations were detected. CONCLUSIONS: Our results indicate that elevated urine levels of the endogeneous psychotomimetic molecule bufotenine may play a role in ASD and schizophrenia, and can be correlated with hyperactivity scores in autism.
Assuntos
Transtorno Autístico/urina , Bufotenina/urina , Esquizofrenia/urina , Adulto , Escalas de Graduação Psiquiátrica Breve , Bufotenina/análise , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Masculino , Espectrometria de Massas , Projetos de Pesquisa , Regulação para Cima , Adulto JovemRESUMO
Phenylethylamine (PEA) is an endogenous amine that is structurally and pharmacologically related to amphetamine. Urinary PEA excretion is significantly higher in paranoid chronic schizophrenics than in nonparanoid chronic schizophrenics and normal controls. Diet, hospitalization, and medication do not account for differences in PEA concentrations. These findings offer some indication that PEA may be an endogenous amphetamine.
Assuntos
Fenetilaminas/urina , Esquizofrenia Paranoide/urina , Doença Crônica , Dieta , Hospitalização , Humanos , Esquizofrenia/urinaRESUMO
OBJECTIVE: The level of various specific biomarkers of oxidative stress in plasma from schizophrenic patients, as well as biomarkers (the level of isoprostanes) in urine in schizophrenic patients was described. The aim of our present study was to evaluate biomarkers of oxidative stress by oxidative/nitrative modifications of plasma proteins (by measuring the level of carbonyl groups and 3-nitrotyrosine in proteins) from patients with schizophrenic disorders and from control group. We also investigated the level of low-molecular-weight thiols [glutathione (GSH), cysteine (CSH), cysteinylglycine (CGSH) and homocysteine] in plasma obtained from schizophrenic patients and from healthy volunteers. Patients hospitalized in the 1st and 2nd Psychiatric Department of the Medical University in Lodz, Poland were interviewed with a special questionnaire (treatment, course of diseases, dyskinesis and other extrapyramidal syndromes). According to DSM-IV criteria, all patients had a diagnosis of paranoid type. They were treated with antipsychotic drugs (clozapine, risperidone, olanzapine). The mean duration of schizophrenia was about 5 years. METHODS: Levels of carbonyl groups and 3-nitrotyrosine residues in plasma proteins were measured by ELISA and a competition ELISA, respectively. High-performance liquid chromatography was used to analyze free thiols in plasma. RESULTS: We observed a statistically increased level of biomarkers of oxidative/nitrative stress such as carbonyl groups or 3-nitrotyrosine in plasma proteins from schizophrenic patients. In schizophrenic patients the amount of homocysteine in plasma was higher compared with the control group; the level of GSH, CSH and CGSH was decreased. This indicates that reactive oxygen species and reactive nitrogen species may stimulate oxidative/nitrative modifications of plasma proteins in schizophrenic patients. CONCLUSION: Considering the data presented in this study, we suggest that the amount of carbonyl groups and 3-nitrotyrosine in plasma proteins may be important indicators of protein damage in vivo in schizophrenia.
Assuntos
Proteínas Sanguíneas/análise , Estresse Oxidativo , Esquizofrenia/metabolismo , Adulto , Biomarcadores/sangue , Biomarcadores/urina , Cromatografia Líquida de Alta Pressão , Cisteína/sangue , Dipeptídeos/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Glutationa/sangue , Homocisteína/sangue , Humanos , Masculino , Esquizofrenia/sangue , Esquizofrenia/urina , Tirosina/análogos & derivados , Tirosina/sangueRESUMO
BACKGROUND: Abnormal cell membrane composition and functional cobalamin (vitamin B(12)) deficiency was reported in schizophrenic individuals. We aimed to investigate the relationship between cobalamin state and cell membrane composition in patients with schizophrenia. METHODS: Malondialdehyde (MDA), cholesterol, and phospholipid classes in the erythrocyte membranes of 18 schizophrenic and 20 healthy individuals of the same age and sex distribution were determined. Serum vitamin B(12), plasma total homocysteine, serum folate, and urine methylmalonic acid (uMMA) concentrations were measured in both groups. RESULTS: In the schizophrenic group, uMMA, membrane MDA, membrane cholesterol, membrane phosphatidylinositol concentrations were significantly higher and the membrane phosphatidylserine concentrations were lower than the control group values. In schizophrenic individuals, uMMA concentrations have a significant positive correlation with membrane MDA and a negative correlation with membrane cholesterol concentrations (P<0.05). The negative correlation of uMMA with membrane cholesterol concentrations may be a biological response to the increased membrane rigidity. Also, a free radical elevation related to the elevated uMMA concentrations in the erythrocyte membrane, might reflect the role of methylmalonic acid (MMA) in membrane damage. CONCLUSION: Our present findings suggest that, functional vitamin B(12) deficiency representing itself by MMA elevations in schizophrenic individuals could damage cell membrane.
Assuntos
Membrana Eritrocítica/metabolismo , Ácido Metilmalônico/urina , Esquizofrenia/urina , Deficiência de Vitamina B 12/urina , Adulto , Feminino , Humanos , MasculinoRESUMO
Agranulocytosis is a rare documented side effect of clozapine which can be associated with grave consequences. When it is associated with other blood dyscrasia, prognosis worsens further. In literature, there are very few cases of pancytopenia and bicytopenia caused by clozapine. We present a case of bicytopenia (reduced white and red blood cells' counts) caused by clozapine within a month of therapy and complicated by a Klebsiella pneumoniae infection. Patient improved in 3 weeks after stopping clozapine along with medical management in the Intensive Care Unit. Such side effects, though rare, can be life threatening and warrants intermittent complete blood monitoring besides regular assessment of granulocytes and neutrophils when any patient is prescribed clozapine.
Assuntos
Anemia/induzido quimicamente , Antipsicóticos/efeitos adversos , Clozapina/efeitos adversos , Leucopenia/induzido quimicamente , Contagem de Células Sanguíneas , Humanos , Infecções por Klebsiella/sangue , Infecções por Klebsiella/urina , Klebsiella pneumoniae , Masculino , Pessoa de Meia-Idade , Esquizofrenia/sangue , Esquizofrenia/tratamento farmacológico , Esquizofrenia/urinaRESUMO
Stress plays a significant role in schizophrenia from disease onset to exacerbation of psychotic symptoms. Allostatic load (AL) is a measure of cumulative stress to the organism. This study is an extension of our previous work on AL and its relationship to brain structures. Here, we further determined whether elevated AL is a function of illness chronicity, or if it is already present early in the course of schizophrenia. AL was compared in schizophrenia patients early in the illness (within 5 years of disease onset), patients with chronic schizophrenia (more than 5 years of illness), and two groups of healthy controls that were age-and sex-matched to the two patient groups. This work is presented with an expanded sample and includes about two-thirds of the participants who were previously reported. We found that patients with early psychosis had significantly elevated AL score compared with their age-matched controls (p = 0.005). Chronic course patients also had elevated AL compared with age-matched controls (p = 0.003). Immune and stress hormone AL subcomponents were nominally higher in early-stage patients compared with controls (p = 0.005 and 0.04, respectively). Greater AL was also associated with more severe positive psychotic symptoms in early-stage patients (r = 0.54, p = 0.01). Elevated levels of allostatic load are already present in the early years of the schizophrenia illness, particularly in patients with more severe psychotic symptoms. AL may be a useful evaluation for the need of early intervention on psychosomatic comorbidity.
Assuntos
Alostase/fisiologia , Transtornos Psicóticos , Esquizofrenia , Adulto , Biomarcadores/sangue , Biomarcadores/urina , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/sangue , Transtornos Psicóticos/fisiopatologia , Transtornos Psicóticos/urina , Esquizofrenia/sangue , Esquizofrenia/fisiopatologia , Esquizofrenia/urina , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Cannabis use disorders (CUD) are common in schizophrenia (~25%) compared to the general population (~3%). Tetrahydrocannabinol (THC), the principal psychoactive component in cannabis is fat-soluble, resulting in an extended period for cannabinoid elimination. While detection of cannabinoids in urine is indicative of prior cannabis exposure, time of last use is difficult to verify sustained abstinence for extended periods (e.g., 28-days) in chronic cannabis users. Therefore, we evaluated the utility of a sustained cannabis abstinence paradigm in patients with schizophrenia and non-psychiatric controls. METHODS: Cannabis dependent patients (n=19) and controls (n=20) underwent 28-days of monitored cannabis abstinence facilitated with contingency management. Urine samples were taken twice weekly. Abstinence was evaluated using 1) Self-report; 2) Qualitative biochemical confirmation using MEDTOX; and 3) in a subset of participants (schizophrenia, n=13; controls, n=13) gas chromatography-mass spectrometry (GC-MS) was performed to obtain quantitative creatinine-normalized carboxy-THC (THC-COOH) metabolite levels <20ng/mL). Subjective assessments were used to assess behavioral correlates of cannabis abstinence and further supported time-dependent abstinence trajectories. RESULTS: Abstinence rates of 42.1% (8/19) in patients and 55% (11/19) in controls (p=0.53) were observed. Increased cannabis withdrawal symptoms in both patients and controls supported abstinence. DISCUSSION: Our results suggest a feasible method for identification of short-term cannabis abstinence in individuals with schizophrenia at rates comparable to controls. Monitoring sustained abstinence may have implications for potential interventions for CUDs in schizophrenia.
Assuntos
Abuso de Maconha/complicações , Abuso de Maconha/terapia , Esquizofrenia/complicações , Adulto , Biomarcadores/urina , Escolaridade , Humanos , Masculino , Abuso de Maconha/urina , Esquizofrenia/urina , Autorrelato , Síndrome de Abstinência a Substâncias , Cooperação e Adesão ao Tratamento , Resultado do TratamentoRESUMO
BACKGROUND: Rates of cannabis use among patients with schizophrenia are high, however little is understood about clinical effects of continued cannabis use and cessation after illness onset. Therefore, we investigated the effects of 28-days of cannabis abstinence on psychotic and depressive symptomatology in cannabis dependent patients with schizophrenia. METHOD: Males with cannabis dependence and co-morbid schizophrenia (n=19) and non-psychiatric controls (n=20) underwent 28-days of monitored cannabis abstinence. Clinical symptoms were assessed at baseline and then weekly. Abstinence was encouraged using weekly therapy sessions and contingency reinforcement, confirmed by twice-weekly urine assays. RESULTS: Forty-two percent (8/19) of patients and 55% (11/20) of controls achieved 28-days of sustained cannabis abstinence. In patients, PANSS subscores did not change over time irrespective of abstinence status. In contrast, patient abstainers demonstrated a more pronounced reduction in depression scores compared to non-abstainers, however, the Abstinence Status x Time interaction was non-significant. DISCUSSION: Short-term (28-days) cannabis abstinence is not associated with improvement in psychotic symptoms, but may be associated with improvement in depressive symptomatology in patients with schizophrenia. Future studies employing larger samples as well as a continuous cannabis-using group may help to better characterize the causal effects of cannabis on symptom outcomes in this disorder.
Assuntos
Abuso de Maconha/complicações , Abuso de Maconha/terapia , Esquizofrenia/complicações , Adulto , Biomarcadores/urina , Comorbidade , Depressão , Humanos , Estudos Longitudinais , Masculino , Abuso de Maconha/psicologia , Abuso de Maconha/urina , Escalas de Graduação Psiquiátrica , Esquizofrenia/urina , Psicologia do Esquizofrênico , Síndrome de Abstinência a Substâncias , Cooperação e Adesão ao TratamentoRESUMO
Elevated systemic oxidative stress levels of 8-oxoGuo and 8-oxodG have been reported in individuals with severe mental illness (SMI). As no previous studies have addressed the link between local levels of 8-oxoGuo and 8-oxodG in the central nervous system (CNS), measured in cerebrospinal fluid (CSF), and urinary systemic levels, we employed autopsy-based material to elucidate this aspect. Additionally, we investigated the impact of 8-oxoGuo and 8-oxodG levels on the prevalence of somatic co-morbidities. Based on post mortem samples from deceased individuals with SMI (Nâ¯=â¯107), we found significantly elevated urinary levels of both 8-oxoGuo and 8-oxodG compared to mentally healthy living controls. While we found an association between urinary and CSF 8-oxodG levels (râ¯=â¯0.50, Pâ¯<â¯0.001), a similar correlation was not evident for 8-oxoGuo (râ¯=â¯0.15, Pâ¯=â¯0.16). Additionally, the two r-values were significantly different (Pâ¯<â¯0.001). Neither marker in urine or CSF was associated with obesity-related variables, metabolic syndrome or type 2 diabetes. The post mortem interval did not affect the results, but the agonal phase seemingly introduced bias. This study provided novel insights into the cellular oxidative stress levels in individuals with SMI. We demonstrated that increased oxidative stress locally and systemically is correlated and is a clear phenomenon in SMI. Although post mortem measurements contain some weaknesses, our study indicates DNA as the main site of oxidative stress modifications in the CNS in SMI. This may provide novel opportunities for treatment modalities. Additionally, our study demonstrated the applicability of post mortem material investigating systemic and local 8-oxoGuo and 8-oxodG levels.
Assuntos
Desoxiguanosina/análogos & derivados , Guanosina/análogos & derivados , Transtornos Mentais/líquido cefalorraquidiano , Estresse Oxidativo/genética , 8-Hidroxi-2'-Desoxiguanosina , Idoso , Autopsia , Transtorno Bipolar/líquido cefalorraquidiano , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/urina , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/fisiopatologia , Desoxiguanosina/líquido cefalorraquidiano , Desoxiguanosina/urina , Depressão/líquido cefalorraquidiano , Depressão/fisiopatologia , Depressão/urina , Feminino , Guanosina/líquido cefalorraquidiano , Guanosina/urina , Humanos , Masculino , Transtornos Mentais/fisiopatologia , Transtornos Mentais/urina , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Esquizofrenia/líquido cefalorraquidiano , Esquizofrenia/fisiopatologia , Esquizofrenia/urinaRESUMO
During periods of psychological stress, excess amounts of free radicals are produced, and they play an important role in the pathophysiological process. Bilirubin oxidative metabolites, biopyrrins, are generated from bilirubin as a result of this scavenging action against free radicals. We investigated whether the urinary excretion of biopyrrin is altered during the psychotic state in patients with schizophrenia. Biopyrrin concentrations in urine of 15 patients with schizophrenia and 100 age-matched healthy subjects were measured by enzyme-linked immunosorbent assay with an anti-bilirubin antibody. Urine samples were obtained from the patients on first admission (acute state), 1 month after admission (sub-acute state), and on discharge (remission state). Urinary concentrations of biopyrrins in patients with schizophrenia on admission were significantly higher than those in the controls. Response to treatment was associated with a significant decrease in the concentrations of biopyrrins. Moreover, urinary concentrations of biopyrrins were still significantly higher in patients with schizophrenia in the sub-acute and remission states than in the controls. These results demonstrated an increase in urinary biopyrrins in patients with schizophrenia and a decrease with recovery from the psychotic state. These findings indicate that the urinary biopyrrin level is a possible indicator that can be useful in the continuous monitoring of psychotic states in clinical practice.
Assuntos
Bilirrubina/urina , Esquizofrenia/urina , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Espécies Reativas de OxigênioRESUMO
BACKGROUND: Asking psychiatric in-patients about their drug consumption is unlikely to yield reliable results, particularly where alcohol and illicit drug use is involved. The main aim of this study was to compare spontaneous self-reports of drug use in hospitalized psychiatric patients to biological measures of same. A secondary aim was to determine which personal factors were associated with the use of tobacco, alcohol, and illicit drugs as indicated by these biological measures. METHODS: The consumption of substances was investigated using biological measures (urine cotinine, cannabis, opiates, cocaine, amphetamines and barbiturates; blood carbohydrate-deficient transferrin [CDT] and gamma-glutamyl transferase [GGT]) in 486 consecutively admitted psychiatric patients, one day following their hospitalization. Patients' self-reports of alcohol, tobacco and illicit drugs consumption were recorded. Socio-professional and familial data were also recorded. RESULTS: The results show a low correlation between biological measures and self-reported consumption of alcohol and illicit drugs. Fifty-two percent of the patients under-reported their consumption of illicit drugs (kappa=.47). Patients with schizophrenia and personality disorders were more likely to disclose their illicit drug consumption relative to patients suffering from mood disorders and alcohol dependence. Fifty-six percent of patients underreported alcohol use, as evaluated by CDT (kappa=.2), and 37% underreported when using the CDT+GGT measure as an indicator. Smoking appeared to be reported adequately. In the study we observed a strong negative correlation between cannabis use and age, a strong correlation between tobacco and cannabis use, and correlations between tobacco, cannabis and alcohol consumption. CONCLUSION: This study is the first to compare self-reports and biological measures of alcohol, tobacco and illicit drug uses in a large sample of inpatients suffering from various categories of psychiatric illnesses, allowing for cross-diagnosis comparisons.
Assuntos
Alcoolismo/psicologia , Drogas Ilícitas , Transtornos Mentais/psicologia , Fumar/psicologia , Detecção do Abuso de Substâncias , Transtornos Relacionados ao Uso de Substâncias/psicologia , Revelação da Verdade , Adolescente , Adulto , Alcoolismo/epidemiologia , Alcoolismo/urina , Comorbidade , Cotinina/urina , Feminino , Humanos , Drogas Ilícitas/urina , Masculino , Transtornos Mentais/epidemiologia , Transtornos Mentais/urina , Pessoa de Meia-Idade , Transtornos da Personalidade/epidemiologia , Transtornos da Personalidade/psicologia , Transtornos da Personalidade/urina , Esquizofrenia/epidemiologia , Esquizofrenia/urina , Psicologia do Esquizofrênico , Fumar/epidemiologia , Fumar/urina , Estatística como Assunto , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/urina , Transferrina/análogos & derivados , Transferrina/metabolismo , gama-Glutamiltransferase/sangueRESUMO
Cross-sectional studies of the effects of cannabis on cognition in schizophrenia have produced mixed results. Heavy and persistent cannabis use in schizophrenia is a common clinical problem, and effects of controlled abstinence from cannabis in these patients have not been carefully evaluated. The present study sought to determine the effects of cannabis abstinence on cognition in patients with schizophrenia and co-occurring cannabis dependence. We utilized a 28-day cannabis abstinence paradigm to investigate the state-dependent effects of cannabis on select cognitive outcomes in cannabis-dependent patients with schizophrenia and non-psychiatric controls. Nineteen patients and 20 non-psychiatric male cannabis-dependent participants underwent 28 days of cannabis abstinence. Cognition was assessed on day 0, 14, and 28 using a comprehensive neuropsychological battery. Clinical symptoms were assessed weekly. Abstinence was facilitated by contingency reinforcement confirmed by twice weekly urinalysis. Forty-two percent of patients and 55% of controls achieved end-point abstinence (p=0.53), which was biochemically-verified (day 28 urinary THC-COOH <20 ng/ml). In this preliminary study, schizophrenia-abstainers demonstrated improvements in Hopkins Verbal Learning Test-Revised (HVLT-R) performance over time [F(2,14)=4.73, p<0.03] (d=1.07). Lesser improvements on HVLT-R were observed in non-psychiatric control abstainers (d=0.66), and with abstinence on other cognitive test measures, in both patients and controls. Verbal memory and learning may improve in schizophrenia and control subjects with cannabis abstinence, but larger more definitive studies are needed. Our findings underscore the importance of developing effective interventions for cannabis use disorders in schizophrenia.
Assuntos
Transtornos Cognitivos/etiologia , Abuso de Maconha/complicações , Esquizofrenia/complicações , Síndrome de Abstinência a Substâncias/complicações , Adulto , Creatinina/urina , Estudos Transversais , Dronabinol/metabolismo , Dronabinol/urina , Feminino , Humanos , Masculino , Abuso de Maconha/urina , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos , Esquizofrenia/urina , Autorrelato , Estatísticas não Paramétricas , Fatores de Tempo , Adulto JovemRESUMO
The present study compared retrospectively in a clinical non-experimental setting the efficacy of buprenorphine (BUP) in different subgroups of dually diagnosed and non-dually diagnosed opioid-dependent patients: all the subjects included in the study showed severe long-lasting heroin addiction and 68.4% were affected by psychiatric comorbidity. Participants (206) (mean age 32.2+/-8.9, 177 males-29 females) were applicants to a long-term buprenorphine treatment program (mean doses 7.9+/-0.42 mg). Aim of the study was to evaluate dual diagnosis variables possibly influencing retention rate and abstinence from illicit drugs. The patients were divided into 5 subgroups on the basis of dual diagnosis: group 1: major depression (MD) 29.61%; group 2: generalized anxiety (GAD) (11.2%); group 3: personality disorders (PD), antisocial-borderline (21.84%); group 4: schizophrenia (SC)(6.3%); group 5: substance use disorder without overt psychiatric comorbidity (SUD) (31.1%). Group 1 patients affected by MD showed the highest retention rate at 12 months (72.1%) in comparison with the other groups of patients: group 2 GAD (39.1%), group 3 PD (17.8%), group 4 SC (7.7%) and group 5 SUD, without comorbidity (45.3%) (p=0.006, p<0.001, p<0.001, p=0.002). Similarly, at 12 months, the patients affected by MD showed less risk of illicit opioid use (16.4%) than those affected by GAD (34.8%), PD (42.2%), SC (53.8%) and SUD without comorbidity (34.4%) (p=0.06, p=0.003, p=0.008, p=0.017). When evaluated on the whole sample, retention rate was not influenced by dose. In contrast, the higher BUP doses were associated with less risk of illicit opioid use, than lower doses (p<0.001). Multivariate analysis and factor analysis showed a greater association of outcome measures (retention rate and negative urines rate) with comorbid diagnosis (depression) (respectively 0.64) than with buprenorphine doses (respectively 0.54). Our data need to be interpreted with caution because of the retrospective methodology applied to a clinical non-experimental setting. BUP seems to be more effective in opioid-dependent patients affected by depression, probably due to the kappa opioid-receptors antagonist action, counteracting dysphoria, negativism and anxiety. High doses of BUP appear to predict a better outcome, in terms of negative urines, but not in terms of retention.
Assuntos
Buprenorfina/uso terapêutico , Dependência de Heroína/diagnóstico , Dependência de Heroína/tratamento farmacológico , Entorpecentes/uso terapêutico , Adulto , Ansiedade/complicações , Ansiedade/diagnóstico , Ansiedade/tratamento farmacológico , Ansiedade/urina , Buprenorfina/urina , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/urina , Relação Dose-Resposta a Droga , Feminino , Dependência de Heroína/complicações , Dependência de Heroína/urina , Humanos , Masculino , Análise Multivariada , Entorpecentes/urina , Transtornos da Personalidade/complicações , Transtornos da Personalidade/diagnóstico , Transtornos da Personalidade/tratamento farmacológico , Transtornos da Personalidade/urina , Estudos Retrospectivos , Esquizofrenia/complicações , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico , Esquizofrenia/urina , Fatores de Tempo , Resultado do TratamentoRESUMO
It has been suggested that patients with schizophrenia develop higher levels of oxidative stress, which may contribute to deteriorating mental illness. In order to examine oxidative stress in the early stages of severe mental illness, we examined the levels of systemic Deoxyribonucleic Acid (DNA) and Ribonucleic Acid (RNA) oxidation, 8-oxo-7,8-dihydro-2'-deoxyguanosine and 8-oxo-7,8-dihydroguanosine, perceived stress and recent life events in patients at ultra high-risk (UHR) of developing psychosis, in antipsychotic naïve patients with first-episode schizophrenia (FES), and in healthy controls. We included 41 UHR patients, 35 FES patients, and 29 healthy controls. There was no difference in the level of DNA/RNA oxidative damage between UHR patients and FES patients compared with healthy controls. We found no association between levels of DNA/RNA oxidative damage and perceived stress/life events. Based on the results, we suggest that DNA and RNA oxidative markers are not increased during the early stages of illness, but further longitudinal studies in first-episode psychosis should be carried out to examine whether DNA and RNA oxidative damage are potential markers of severe illness.
Assuntos
Dano ao DNA , DNA/urina , Estresse Oxidativo , RNA/urina , Esquizofrenia/urina , Psicologia do Esquizofrênico , 8-Hidroxi-2'-Desoxiguanosina , Adolescente , Adulto , Biomarcadores/urina , Estudos de Casos e Controles , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Feminino , Guanosina/análogos & derivados , Guanosina/urina , Humanos , Masculino , Fatores de Risco , Estresse Psicológico/psicologia , Adulto JovemRESUMO
Measurement of urinary 3-methoxy-4-hydroxyphenethylene glycol (MHPG) levels has been suggested as possibly being important in elucidating the role of central noradrenergic function in affective illnesses. The influence on urinary MHPG excretion of the state variables of physical activity and stress has not been clearly defined in previous studies. During a baseline medication-free period, 24 hospitalized depressed female patients underwent a five-day protocol including an eight-hour period of either enhanced or restricted activity. Throughout the protocol, independent measurements of telemetered mobility and stale anxiety were obtained. There were no significant effects of physical activity on urinary MHPG levels. Furthermore, baseline urinary MHPG levels and baseline state anxiety did not covary significantly. However, within-individual analyses yielded a highly significant relationship between changes in urinary MHPG levels and changes in state anxiety. The data suggested that those patients with lower baseline MHPG levels were those more prone to experience increased anxiety under environmentally "activating" circumstances.