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1.
Iran J Allergy Asthma Immunol ; 18(3): 262-268, 2019 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-31522433

RESUMO

A growing body of evidence suggests the existence of abnormalities in the immune system of schizophrenic patients. The current study examined serum levels of interleukin (IL) -1ß, IL-6, IL-2,interferon(IFN) -γ, and tumor necrosis factor(TNF)-α in schizophrenic patients before and after treatment with risperidone and correlated levels of these cytokines with symptomatology. The study group consisted of 24 schizophrenic patients as defined by Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria and 24 healthy controls. Serum cytokine levels were examined using enzyme-linked immunosorbent assay (ELISA). Schizophrenic symptomatology was assessed with the Positive and Negative Syndrome Scale (PANSS) questionnaire. The serum levels of TNF-α, IL-1ß and IL-6 were significantly higher in participants before treatment compared with the healthy controls and after treatment (p<0.001). IFN-γ and IL-2 levels were significantly lower in participants after treatment compared with before treatment and the healthy controls (p<0.001). Except for IL-6 (p<0.05), there was no significant difference in the levels of TNF-α and IL-1ß between the patients receiving treatment and the healthy subjects. Moreover, there was no significant difference in levels of IFN-γ and IL-2 between patients before treatment and the healthy subjects. There were no significant correlations between the concentration of cytokines studied and the PANSS. Positive intercorrelations between the production of IFN-γ and IL-2 were detected for sums of all groups(r=0.33, p=0.005). Clinical improvement of treated patients was associated with a reduction in the studied cytokines. It seems that changes in the cytokines level may play a significant role in the psychopathology of these patients.


Assuntos
Antipsicóticos/uso terapêutico , Citocinas/sangue , Risperidona/uso terapêutico , Esquizofrenia/sangue , Esquizofrenia/tratamento farmacológico , Adulto , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Biomarcadores , Estudos de Casos e Controles , Feminino , Humanos , Mediadores da Inflamação/sangue , Masculino , Risperidona/administração & dosagem , Risperidona/efeitos adversos , Esquizofrenia/diagnóstico , Esquizofrenia/imunologia , Células Th1/imunologia , Células Th1/metabolismo
2.
Med Hypotheses ; 130: 109279, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31383340

RESUMO

BACKGROUND: The hypotheses of autoimmune, allergic or infectious etiology of severe mental illness have been reported in the scientific literature repeatedly. The main objective of this work is to study the relationship of inflammatory, autoimmunity or recent infection markers with the fact of suffering Severe Mental Disorders (SMD). METHODS: In the present case-control study, adult patients with a diagnosis of SMD were compared with controls who underwent routine health checks that included analytical control. Cases with psychosis substance-induced and controls with diagnosis of any psychiatric illness were excluded. In both groups, patients with chronic inflammatory diseases or intercurrent infectious disease were also excluded. A set of common analytical parameters, markers of infectious diseases and inflammatory markers were retrieved for both groups, as well as demographic and clinical data. RESULTS: A total of 212 subjects (81 cases and 131 controls) were recruited. From cases, 70 (86.4%) have a diagnosis of Schizophrenia Disease (SD) and 11 (13.6%) of Schizoaffective Disorder (SAD). In the multivariate model the female sex (OR 0.24, 95% CI 0.12-0.46) and the neutrophil-lymphocyte ratio (OR 3.00, 95% CI 1.91-4.70) were associated with the fact of being case. CONCLUSIONS: Patients with SMD seem to have higher inflammatory markers compared to the general population, being the neutrophil-lymphocyte ratio, the marker associated with more strength. The role of inflammatory processes in the etiology of this type of disorders, if confirmed, opens interesting and innovative therapeutic possibilities.


Assuntos
Inflamação/metabolismo , Linfócitos/citologia , Transtornos Mentais/sangue , Neutrófilos/citologia , Transtornos Psicóticos/sangue , Esquizofrenia/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Transtornos Mentais/imunologia , Pessoa de Meia-Idade , Análise Multivariada , Transtornos Psicóticos/imunologia , Esquizofrenia/imunologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-31364826

RESUMO

Objective: The evidence linking schizophrenia and total and unconjugated bilirubin is primarily from retrospective studies. To overcome this limitation, we conducted a prospective study of total and unconjugated bilirubin levels of patients diagnosed with schizophrenia or bipolar affective disorder. Methods: Serum total and unconjugated bilirubin levels were compared between patients diagnosed with schizophrenia (n = 50) and bipolar affective disorder (n = 43) (ICD-10 criteria) admitted to an inpatient psychiatric unit of a tertiary hospital in India. The study was conducted between October 2013 and July 2015. Results: The median serum levels (mg/dL) of total and unconjugated bilirubin were significantly higher (P = .027 and P = .004, respectively) among patients with schizophrenia compared to those with bipolar affective disorder. Analysis of covariance revealed that unconjugated bilirubin was significantly higher (P = .029) in patients with schizophrenia compared to those with bipolar affective disorder, even after controlling for the effects of age, sex, and medications. Conclusions: In this prospective study, serum levels of unconjugated bilirubin were significantly higher in patients with schizophrenia compared to patients with bipolar affective disorder. The findings suggest that serum unconjugated bilirubin could be a potential marker for schizophrenia. However, the results need to be replicated in a larger sample including patients living in the community.


Assuntos
Bilirrubina/sangue , Transtorno Bipolar/sangue , Esquizofrenia/sangue , Adulto , Biomarcadores/sangue , Transtorno Bipolar/terapia , Estudos Transversais , Feminino , Hospitalização , Humanos , Masculino , Serviços de Saúde Mental , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Esquizofrenia/terapia , Índice de Gravidade de Doença
4.
Nord J Psychiatry ; 73(8): 515-521, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31464540

RESUMO

The purpose of the article: Brain-derived neurotrophic factor (BDNF) and matrix metalloproteinase-9 (MMP-9) are involved in the processes of neurogenesis, synaptic plasticity, learning and memory. Growing number of studies shows a relationship between BDNF or MMP-9 and schizophrenia. Also, BDNF and MMP-9 levels may be affected by metabolic parameters, such as obesity or dyslipidemia. Our hypothesis is that alterations of BDNF or MMP-9 levels in schizophrenia might be secondary to metabolic abnormalities, often found among schizophrenia patients. Materials and methods: We have compared BDNF and MMP-9 between patients with schizophrenia (n = 64, age 49 ± 8.2 y) and healthy controls (n = 32, age 51 ± 8.9 y) in the context of cardio-metabolic parameters. Serum levels of BDNF and MMP-9 were measured using ELISA test, body composition parameters were determined using bioelectric impedance analysis. Results and conclusions: Our results showed significantly lowered serum BDNF concentration in the schizophrenia group (schizophrenia: 23.8 ± 7.83 ng/mL, control: 27.69 ± 8.11 ng/mL, p = 0.03). Serum MMP-9 concentration in schizophrenia group did not differ compared with the control group (schizophrenia: 456.8 ± 278.4 ng/mL, control: 341.5 ± 162.4 ng/mL, p = 0.07). After adjusting for age, all anthropometric parameters, body composition and laboratory tests BDNF were still significantly lower in the schizophrenia group. However, MMP-9 became significantly elevated in the schizophrenia group after adjusting for several anthropometric and body composition covariates. Our results confirmed reduced serum BDNF concentration in patients with schizophrenia. Also, this reduction seems to be independent of metabolic abnormalities. On the other hand, our hypothesis that MMP-9 level in schizophrenia is altered due to metabolic abnormalities might be true.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Metaloproteinase 9 da Matriz/sangue , Esquizofrenia/sangue , Esquizofrenia/diagnóstico , Adulto , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
5.
Hereditas ; 156: 23, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31297041

RESUMO

Background: At present, the schizophrenia diagnoses are based on the clinical symptoms and behaviors neglecting the laboratory test indicators. Results: To better investigate the diagnostic potential of miRNAs for schizophrenia, we selected 14 candidate miRNAs and examined their expressions in the serums of 40 schizophrenia patients and 40 healthy controls by qRT-PCR. Ultimately three abnormally expressed microRNAs were identified, i.e., miR-34a-5p, miR-432-5p and miR-449a. Then, binary regression analysis was employed to combine 3 dysregulated miRNAs. ROC analysis revealed that the AUC of the combination of miR-432-5p + miR-449a in serums was 0.841 (95% CI: 0.791~0.887) with 90% sensitivity and 80% specificity. The AUC of the combination of miR-34a-5p + miR-432-5p + miR-449a in serums was 0.843 (95% CI: 0.791~0.887) with 90% sensitivity and 77.5% specificity. The results indicated that the combined model of miR-432-5p + miR-449a and miR-34a-5p + miR-432-5p + miR-449a have better prediction performances. Conclusions: The study concludes that the two miRNAs combinations have the potential to be used as biomarkers for schizophrenia diagnoses. The finding may be conducive to overcoming the dilemmas faced by current schizophrenia diagnosis.


Assuntos
Biomarcadores , MicroRNAs/genética , Esquizofrenia/diagnóstico , Esquizofrenia/genética , Adulto , Estudos de Casos e Controles , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , MicroRNAs/sangue , Prognóstico , Curva ROC , Esquizofrenia/sangue , Transcriptoma , Adulto Jovem
6.
J Mol Neurosci ; 69(1): 69-74, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31256336

RESUMO

The fibroblast growth factor (FGF) system has been suggested to be involved in the development of schizophrenia (SCZ). However, the potential roles of all FGFs have not been well studied in the literature. Here, we investigated the concentration of peripheral blood fibroblast 10 (FGF10) in patients with SCZ to determine whether FGF10 could serve as a biomarker for SCZ. We recruited 130 SCZ patients (57 first-episode, drug-free patients and 73 chronically medicated patients) and 111 healthy controls. Our results showed that serum FGF10 levels were significantly decreased in SCZ patients when compared with controls. Sub-group analyses revealed that both first-episode, drug-free patients and chronically medicated patients had lower levels of FGF10 than controls. Moreover, both male and female SCZ patients had significantly decreased blood FGF10 levels relative to control subjects. Using a receiver operating characteristic curve, the optimal cutoff value of FGF10 level as an indicator for diagnosis of first-onset SCZ patients was projected to be 152.3 pg/ml, which yielded a sensitivity of 0.658 and specificity of 0.649, with an area under the curve of 0.665 (95% confidence interval, 0.577-0.754). Taken together, our results are the first to demonstrate an association between FGF10 and SCZ, providing further evidence for the neurotrophic factor hypothesis of SCZ.


Assuntos
Fator 10 de Crescimento de Fibroblastos/sangue , Esquizofrenia/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino
7.
PLoS One ; 14(7): e0219454, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31291336

RESUMO

The association of latent toxoplasmosis with mental disorders in general and with schizophrenia in particular was noticed in the mid-1950s. In subsequent years, the role of Toxoplasma gondii was established based on its ability to survive for long periods of time in the nerve cells of the brain. The acute manifestations of the infection include psychopathic symptoms resembling those of schizophrenia. In the former USSR, and in other parts of the world, a number of studies were performed with respect to the association of latent toxoplasmosis and schizophrenia. However, with the dissolution of the USSR at the beginning of the 1990s, studies on the subject were halted due to financial problems and have resumed only recently. The reasons for the resumption of such studies in contemporary Russia are related to the progressively increasing incidence of schizophrenia over the last 25-30 years in the country. According to official data, approximately 550 000 persons reported suffering from the disease in 2014. There are reasons to believe that this is only a fraction of the real burden of the disease. Economically, it cost the state no less than approximately US $10 billion. The purpose of the study was to identify the level of toxoplasmosis seroprevalence in patients with verified diagnoses of schizophrenia in comparison to healthy people in Moscow City and in the Moscow region. A total of 155 persons constituted the patients group and 152 healthy people were in the control group. An integrated approach to the diagnosis and comparison of data from the entire spectrum of serological markers of infection was used, including the detection of specific IgM and the determination of IgG concentrations. It was found that among persons with neuropsychiatric disorders, the incidence of cases with latent toxoplasmosis was higher than in the control group. The effect of toxoplasmosis was significant and similar for men and women. Further statistical analyses revealed that among patients with a diagnosis of schizophrenia, the incidence of latent toxoplasmosis was significantly higher than in the control group. These data are in agreement with the results of similar studies in other countries.


Assuntos
Transtornos Mentais/epidemiologia , Esquizofrenia/epidemiologia , Toxoplasmose/epidemiologia , Adolescente , Adulto , Encéfalo/imunologia , Encéfalo/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Transtornos Mentais/sangue , Transtornos Mentais/complicações , Transtornos Mentais/imunologia , Pessoa de Meia-Idade , Moscou/epidemiologia , Neurônios/imunologia , Neurônios/patologia , Federação Russa/epidemiologia , Esquizofrenia/sangue , Esquizofrenia/complicações , Esquizofrenia/imunologia , Estudos Soroepidemiológicos , Toxoplasma/imunologia , Toxoplasma/patogenicidade , Toxoplasmose/sangue , Toxoplasmose/complicações , Toxoplasmose/imunologia , Adulto Jovem
8.
Acta Neuropsychiatr ; 31(4): 202-212, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31178002

RESUMO

OBJECTIVE: Oxidative stress and dysregulated antioxidant defence may be involved in the pathophysiology of schizophrenia. In the present study, we investigated changes in antioxidants and oxidative stress from an acute to a later stable phase. We hypothesised that the levels of oxidative markers are increased in schizophrenia compared with healthy controls; change from the acute to the stable phase; and are associated with the levels of membrane polyunsaturated fatty acids (PUFAs) and symptom severity. METHODS: Fifty-five patients with schizophrenia spectrum disorders, assessed during an acute phase and 5 years later during a stable phase, and 51 healthy controls were included. We measured antioxidants (α-tocopherol, uric acid, albumin and bilirubin), markers of oxidative stress (F2-isoprostane and reactive oxygen metabolites) and membrane fatty acids. Antioxidants and oxidative stress markers were compared in schizophrenia versus healthy controls, adjusting for differences in sex, age and smoking, and changes over time. Associations between symptoms and PUFA were also investigated. RESULTS: In the acute phase, α-tocopherol was significantly higher (p < 0.001), while albumin was lower (p < 0.001) compared with the stable phase. Changes in α-tocopherol were associated with PUFA levels in the acute phase. In the stable phase, schizophrenia patients had higher uric acid (p = 0.009) and lower bilirubin (p = 0.046) than healthy controls. CRP was higher in patients in the stable phase (p < 0.001), and there was no significant change from the acute phase. CONCLUSION: The present findings of change in antioxidant levels in the acute versus stable phase of schizophrenia the present findings suggest that redox regulation is dynamic and changes during different phases of the disorder.


Assuntos
Antioxidantes/análise , Ácidos Graxos Insaturados/sangue , Estresse Oxidativo , Esquizofrenia/sangue , Albumina Sérica/análise , alfa-Tocoferol/sangue , Adulto , Antioxidantes/metabolismo , Bilirrubina/sangue , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Masculino , Esquizofrenia/epidemiologia , Ácido Úrico/sangue
9.
PLoS One ; 14(6): e0216463, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31185023

RESUMO

Schizophrenia has been consistently characterized by abnormal patterns of gene down-regulation, increased restrictive chromatin assemblies, and reduced transcriptional activity. Histone methyltransferase (HMT) mRNA and H3K9me2 levels are elevated in postmortem brain and peripheral blood cells of persons with schizophrenia. Moreover, this epigenomic state likely contributes to the disease, as HMT levels correlate with clinical symptomatology. This manuscript sought to establish the potential therapeutic value of the HMT inhibitor BIX-01294 (BIX). Human peripheral mononuclear cells (PBMC) from 24 individuals with schizophrenia and 24 healthy individuals were cultured in the presence of BIX (5uM or 10uM). Mice were given once daily intraperitoneal injections of BIX (0.5 or 1mg/kg) for one week. Cultured cells, mouse cortex, or striatum was harvested, RNA extracted and RT-PCR conducted for several schizophrenia candidate genes: IL-6, Gad1, Nanog, KLF4, Reln, and Bdnf9a. Total H3K9me2 levels were measured using western blot while H3K9me2 binding to selected genes of interest was conducted using chromatin immunoprecipitation (ChIP). Neuronal subtype-specific BDNF conditional knockdown was conducted using the cre/lox system of mutant animals. Treatment with BIX decreased H3K9me2 and increased selected mRNA levels in cultured PBMCs from both normal controls and participants with schizophrenia. In mice, peripheral administration of BIX decreased cortical H3K9me2 levels and increased schizophrenia candidate gene expression. In BDNF conditional knockdown animals, BIX administration was able to significantly rescue Bdnf9a mRNA levels in ChAT and D1 Bdnf conditional knockdown mice. The results presented in this manuscript demonstrate a potential for further research into the clinical effectiveness of histone modifying pharmacology in the treatment of schizophrenia.


Assuntos
Azepinas/farmacologia , Inibidores Enzimáticos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Código das Histonas/efeitos dos fármacos , Histona Metiltransferases/antagonistas & inibidores , Quinazolinas/farmacologia , Animais , Azepinas/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/genética , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Inibidores Enzimáticos/uso terapêutico , Feminino , Histonas/metabolismo , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Masculino , Camundongos , Mutação , Quinazolinas/uso terapêutico , RNA Mensageiro/genética , Esquizofrenia/sangue , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genética
10.
Psychiatry Res ; 273: 706-711, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-31207856

RESUMO

Toxoplasmosis has been previously associated with an increased risk of having Schizophrenia or Bipolar disorder in several epidemiological studies. The aim of this observational, cross-sectional study was to examine the seroprevalence of Toxoplasma infection in a cohort of Italian psychiatric inpatients and to verify the presence of circulating Toxoplasma gondii DNA in the seropositive subjects. Sixty-three patients affected by bipolar or schizoaffective disorders according to DSM-5 criteria were enrolled. The presence of Toxoplasma infection was firstly examined using an indirect serological method (ELFA), and three different direct PCR-based methods were performed to detect circulating DNA in the seropositive patients. The seroprevalence of infection was 28.6%, with a significant association between higher age and the infection status. PCR, nested-PCR and Real-Time PCR revealed no positive samples for Toxoplasma gondii. This result is in contrast with recent data from case-control studies that detected parasite genome in patients with different neuropsychiatric diagnosis without clinical evidence of acute toxoplasmosis. Our findings are to be interpreted with caution, because of the small sample size, the heterogeneity of enrolled patients and the observational nature of the study. Further studies are needed to better define the clinical features correlated to the seropositive status in neuropsychiatric patients.


Assuntos
Transtorno Bipolar/sangue , DNA de Protozoário/sangue , Esquizofrenia/sangue , Toxoplasma/genética , Toxoplasmose/psicologia , Adulto , Transtorno Bipolar/parasitologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Esquizofrenia/parasitologia , Estudos Soroepidemiológicos , Toxoplasmose/sangue , Toxoplasmose/parasitologia
11.
Psychiatry Res ; 273: 782-787, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-31207866

RESUMO

Evidence indicates that abnormal phospholipase A2 (PLA2) levels and niacin insensitivity are present in individuals with schizophrenia. This study was designed to determine whether differences in plasma calcium-independent phospholipase A2 (iPLA2) and cytosolic phospholipase A2 (cPLA2) exist between those with schizophrenia and healthy controls, and to explore the correlation between PLA2s and the niacin skin reaction in schizophrenic patients. We performed ELISA experiments to measure the concentrations of plasma iPLA2 and cPLA2 and we conducted a series of niacin skin tests on schizophrenic patients from the Chinese Han population. In addition, a meta-analysis of the relationship between PLA2 and schizophrenia was conducted. The plasma concentration of iPLA2 in patients with schizophrenia was significantly higher than that in healthy controls while the plasma concentration of cPLA2 did not differ. The meta-analysis also revealed that the activity level of iPLA2 in individuals with schizophrenia was higher than that in healthy controls, whereas that of cPLA2 was not. Furthermore, a significant positive correlation was found between the concentration of iPLA2 and the score for the skin flushing response within 20 min. The abnormal plasma iPLA2 concentration and its relationship with the niacin skin test in schizophrenic patients has contributed to a deeper understanding of the pathology of schizophrenia, which may in turn provide new insights into the clinical diagnoses and treatment of schizophrenia.


Assuntos
Fosfolipases A2 do Grupo VI/sangue , Fosfolipases A2 Citosólicas/sangue , Esquizofrenia/sangue , Esquizofrenia/diagnóstico , Adulto , Animais , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
12.
Transl Psychiatry ; 9(1): 156, 2019 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-31150013

RESUMO

Currently, the clinical diagnosis of schizophrenia relies solely on self-reporting and clinical interview, and likely comprises heterogeneous biological subsets. Such subsets may be defined by an underlying biology leading to solid biomarkers. A transgenic rat model modestly overexpressing the full-length, non-mutant Disrupted-in-Schizophrenia 1 (DISC1) protein (tgDISC1 rat) was generated that defines such a subset, inspired by our previous identification of insoluble DISC1 protein in post mortem brains from patients with chronic mental illness. Besides specific phenotypes such as DISC1 protein pathology, abnormal dopamine homeostasis, and changes in neuroanatomy and behavior, this animal model also shows subtle disturbances in overarching signaling pathways relevant for schizophrenia. In a reverse-translational approach, assuming that both the animal model and a patient subset share common disturbed signaling pathways, we identified differentially expressed transcripts from peripheral blood mononuclear cells of tgDISC1 rats that revealed an interconnected set of dysregulated genes, led by decreased expression of regulator of G-protein signaling 1 (RGS1), chemokine (C-C) ligand 4 (CCL4), and other immune-related transcripts enriched in T-cell and macrophage signaling and converging in one module after weighted gene correlation network analysis. Testing expression of this gene network in two independent cohorts of patients with schizophrenia versus healthy controls (n = 16/50 and n = 54/45) demonstrated similar expression changes. The two top markers RGS1 and CCL4 defined a subset of 27% of patients with 97% specificity. Thus, analogous aberrant signaling pathways can be identified by a blood test in an animal model and a corresponding schizophrenia patient subset, suggesting that in this animal model tailored pharmacotherapies for this patient subset could be achieved.


Assuntos
Biomarcadores/sangue , Redes Reguladoras de Genes , Esquizofrenia , Transdução de Sinais/genética , Animais , Quimiocina CCL4/sangue , Estudos de Coortes , Modelos Animais de Doenças , Masculino , Proteínas do Tecido Nervoso/genética , Proteínas RGS/sangue , Ratos , Ratos Sprague-Dawley , Ratos Transgênicos , Esquizofrenia/sangue , Esquizofrenia/classificação , Esquizofrenia/genética , Esquizofrenia/imunologia , Sensibilidade e Especificidade
13.
Biol Pharm Bull ; 42(6): 1025-1029, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31155577

RESUMO

Magnesium oxide (MgO) is a widely used laxative. Because many antipsychotic drugs are lipophilic-basic-compounds, their solubility decreases with increasing pH and changes markedly as the pH of the solution approaches their pKa. It is highly important to clarify the effect of co-administration of MgO on the serum drug concentration for effective, safe, and appropriate medication therapy. However, the relationship between MgO administration and the serum concentration of antipsychotic drugs in patients with schizophrenia has not been reported. Therefore, in the present study, we investigated the effect of MgO administration on the concentration of antipsychotic drugs in the blood of patients with schizophrenia. The serum concentrations of biperiden, zotepine, and risperidone were assayed using an LC/MS system. The correlation between the daily dose of MgO and the relative-drug-concentration (rCp) in each patient was examined. As the MgO dose was increased, the risperidone concentration decreased. The correlation coefficient decreased for risperidone, zotepine, and biperiden, in the same order. To clarify the difference in the suppression potency of MgO on the three drugs, the relationship between the physical properties and the correlation coefficients of each drug was carefully examined. A strong correlation was observed between the pKa and the correlation coefficient. Patients with schizophrenia are often prescribed antipsychotic drugs, which have anticholinergic action and tend to suppress gastric acid secretion. We concluded that basic drug absorption might be suppressed due to an increase in the stomach pH following MgO administration. Therefore, MgO co-administration is better to avoid while taking antipsychotic drugs and anticholinergic drugs.


Assuntos
Antipsicóticos/farmacocinética , Laxantes/farmacologia , Óxido de Magnésio/farmacologia , Esquizofrenia/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antipsicóticos/sangue , Biperideno/sangue , Biperideno/farmacocinética , Dibenzotiepinas/sangue , Dibenzotiepinas/farmacocinética , Interações de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Interações Hidrofóbicas e Hidrofílicas , Masculino , Pessoa de Meia-Idade , Risperidona/sangue , Risperidona/farmacocinética , Esquizofrenia/tratamento farmacológico
14.
J Clin Neurosci ; 65: 11-16, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31076249

RESUMO

Schizophrenia (SCH) and drug addiction are chronic disorders that are frequently accompanied by physical diseases, poor nutrition and reduced self-care, all of which are likely to result in vitamin deficiencies. The objective of this study was to compare vitamin levels in SCH patients, substance use disorder (SUD) patients and healthy controls (HCs). The study included 189 SCH patients, 119 SUD patients and 109 HCs. Information on vitamin B12, folic acid and vitamin D levels were retrieved from the hospital's database, and mean values and deficiency/insufficiency were evaluated. Vitamin D deficiency (<30 ng/ml) was more common in the SCH group than in the SUD and HC groups (88.4%, 74.8% and 86.4%, respectively). Although there were no significant differences in folic acid deficiency (<3.0 ng/ml) in the SUD and SCH groups (15.1% and 8.5%, respectively), the incidence of folic acid deficiency was significantly higher in both groups as compared with that in the HC group (5.8%). Significantly higher numbers of patients in the SCH group than in the SUD group had vitamin B12 deficiency (45.5% vs. 28.3%). The prevalence of vitamin B12 deficiency in the SUD group was significantly higher than that the HC group (28.3% vs.11.5%). As compared with the HC group, vitamin D and B12 levels were significantly lower in SCH group, and folic acid and B12 levels were significantly lower in the SUD group. Several vitamin deficiencies appear to be common in both SCH and SUD. Possible reasons should be investigated.


Assuntos
Deficiência de Ácido Fólico/epidemiologia , Esquizofrenia/sangue , Transtornos Relacionados ao Uso de Substâncias/sangue , Deficiência de Vitamina B 12/epidemiologia , Deficiência de Vitamina D/epidemiologia , Adulto , Feminino , Ácido Fólico/sangue , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Vitamina B 12/sangue , Vitamina D/sangue
15.
Asian J Psychiatr ; 43: 105-110, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31125952

RESUMO

The identification of biological markers for psychosis has an impact on its diagnosis, prognosis, and likelihood of treatment response. Tissue plasminogen activator (tPA) is involved in important functions such as synaptic plasticity, long-term potentiation and neurogenesis. Plasminogen activator inhibitor (PAI-1) is the most important inhibitor of tPA. Preliminary studies have shown that schizophrenia patients have lower tPA and higher PAI-1 levels than the general population. The association of tPA and PAI-1 abnormalities with psychotic spectrum disorders, however, remains elusive. Our primary objective was to assess the plasma levels of tPA and PAI-1 in patients experiencing acute psychotic episodes as compared to those in healthy controls. In this prospective case-control study, we collected peripheral blood samples from psychiatric inpatients and healthy age, gender and race-matched subjects and determined plasma levels of tPA and PAI-1 by enzyme-linked immune-absorbent assays. Plasma levels of PAI-1 in patients with schizoaffective disorder were significantly lower as compared to those in control subjects (P = 0.03). tPA was lower in cases as compared to controls although it did not reach statistical significance. Asian patients and controls had lower PAI-1 levels. Further, Asian patients with schizoaffective disorder had significantly lower PAI-1 level compared to Asian patients with schizophrenia. Our results indicate that patients with schizoaffective disorder have lower PAI-1 levels than those with schizophrenia, affective psychosis, and healthy controls. Further studies are warranted to explore the potential of PAI-1 as a biomarker for diagnosing schizoaffective disorder.


Assuntos
Inibidor 1 de Ativador de Plasminogênio/sangue , Transtornos Psicóticos/sangue , Transtornos Psicóticos/diagnóstico , Esquizofrenia/sangue , Esquizofrenia/diagnóstico , Ativador de Plasminogênio Tecidual/sangue , Adulto , Americanos Asiáticos , Biomarcadores/sangue , Estudos de Casos e Controles , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/etnologia , Estudos Prospectivos , Transtornos Psicóticos/etnologia , Esquizofrenia/etnologia
16.
Psychopharmacology (Berl) ; 236(9): 2811-2822, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31098654

RESUMO

RATIONALE: N-3 polyunsaturated fatty acids (n-3 PUFA) influence multiple biochemical mechanisms postulated in the pathogenesis of schizophrenia that may influence BDNF synthesis. OBJECTIVES: A randomized placebo-controlled study was designed to compare the efficacy of a 26-week intervention composed of either 2.2 g/day of n-3 PUFA or olive oil placebo, with regard to symptom severity in first-episode schizophrenia patients. The secondary outcome measure of the study was to describe the association between n-3 PUFA clinical effect and changes in peripheral BDNF levels. METHODS: Seventy-one patients aged 16-35 were enrolled in the study and randomly assigned to the following study arms: 36 to the EPA + DHA group and 35 to the placebo group. Plasma BDNF levels were assessed three times, at baseline and at weeks 8 and 26 of the intervention. BDNF levels were determined in plasma samples using Quantikine Human BDNF ELISA kit. Plasma BDNF level changes were further correlated with changes in the severity of symptoms in different clinical domains. RESULTS: A significantly greater increase in plasma BDNF levels was observed in the intervention compared to the placebo group (Cohen's d = 1.54). Changes of BDNF levels inversely correlated with change in depressive symptoms assessed using the Calgary Depression Rating Scale in Schizophrenia (Pearson's r = - 0.195; p = 0.018). CONCLUSIONS: The efficacy of a six-month intervention with n-3 PUFA observed in first-episode schizophrenia may be related to an increase in BDNF levels, which may be triggered by the activation of intracellular signaling pathways including transcription factors such as cAMP-reactive element binding protein.


Assuntos
Antipsicóticos/administração & dosagem , Fator Neurotrófico Derivado do Encéfalo/sangue , Ácidos Graxos Ômega-3/uso terapêutico , Esquizofrenia/sangue , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Adolescente , Adulto , Biomarcadores/sangue , Método Duplo-Cego , Feminino , Humanos , Masculino , Azeite de Oliva/uso terapêutico , Escalas de Graduação Psiquiátrica , Resultado do Tratamento , Adulto Jovem
17.
Neuropsychobiology ; 78(2): 70-78, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31096226

RESUMO

Schizophrenia is a phenotypically heterogeneous and poorly understood disorder. While its etiology is likely multifactorial, immune system dysfunction has increasingly been implicated in its development. As hallucinations and delusions occur frequently and prominently in autoimmune encephalitis (AE), numerous studies have sought to determine whether a small subset of individuals diagnosed with schizophrenia possess anti-neuronal antibodies implicated in AE. Exploring this possibility is of clinical relevance, as identifying individuals with AE who have been misdiagnosed as having a primary psychotic disorder may allow for the implementation of appropriate immune-related therapies as early as possible in the course of the illness, in order to optimize outcomes, reduce illness chronicity, and minimize adverse events. This qualitative review serves to provide an overview of the existing literature on this topic, as well as to update previously published reviews. Although there is some evidence to suggest that in rare cases AE may be misdiagnosed as a primary psychotic disorder, particularly early in the course of the illness, numerous methodological differences between studies likely account for the highly variable findings, and interpretation of the results is particularly limited by a paucity of cerebrospinal fluid data. Moreover, the prevalence of misdiagnosis in chronic and treatment-resistant populations remains understudied. This is particularly problematic, as treatment resistance may represent an enriched population with respect to the presence of anti-neuronal antibodies, and given that such patients have few evidence-based treatment options available to them beyond clozapine.


Assuntos
Antígenos de Superfície/imunologia , Autoanticorpos/imunologia , Encefalite/imunologia , Doença de Hashimoto/imunologia , Neurônios/imunologia , Esquizofrenia/imunologia , Autoanticorpos/sangue , Autoanticorpos/líquido cefalorraquidiano , Humanos , Esquizofrenia/sangue
18.
Asian J Psychiatr ; 43: 1-6, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059867

RESUMO

BACKGROUND: Adiponectin is a hormone secreted by adipose tissues that is thought to influence lipid and glucose metabolism, and the development of metabolic derangements, including metabolic syndrome (MetS), in schizophrenia. We aim to determine the serum adiponectin levels in Chinese patients with schizophrenia, and explore the relationship between adiponectin levels and metabolic parameters, including MetS and its components. We hypothesized that serum adiponectin levels are similar in schizophrenia patients and controls, but decreased amongst patients on atypical antipsychotics. METHODS: 81 patients and 81 controls were recruited. Anthropometric parameters and fasted blood samples for metabolic measurements were obtained. Serum adiponectin levels were measured using Bioplex assays. RESULTS: There was no difference in median adiponectin levels between schizophrenia patients and controls. Those taking typical antipsychotics alone had lower median adiponectin levels than those on mixed typical and atypical antipsychotics. Serum adiponectin level, controlled for age, gender and body mass index, was positively correlated with high-density lipoprotein cholesterol, and negatively correlated with diastolic blood pressure, total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels in schizophrenia patients. Patients with MetS had lower median adiponectin levels than those without MetS, and serum adiponectin levels decreased as the number of MetS components increased. After adjusting for variables thought to influence MetS, our logistic regression model did not reveal any significant association between adiponectin levels and MetS in schizophrenia patients. CONCLUSION: Our findings highlight the need for more studies focusing on serum adiponectin level and its relationship with MetS in schizophrenia, particularly in those taking typical antipsychotics.


Assuntos
Adiponectina/sangue , Antipsicóticos/farmacologia , Doenças Cardiovasculares , Síndrome Metabólica , Esquizofrenia/sangue , Esquizofrenia/tratamento farmacológico , Adulto , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Esquizofrenia/epidemiologia , Singapura/epidemiologia , Triglicerídeos/sangue
19.
Trials ; 20(1): 229, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31014369

RESUMO

BACKGROUND: The potential of non-invasive repetitive transcranial magnetic stimulation (rTMS) to improve auditory verbal hallucinations (AVH) in schizophrenia patients has been increasingly explored over the past decade. Despite highly promising results, high inter-individual variability of clinical response and ineffective outcomes in a significant number of patients underscored the need to identify factors associated with the clinical response to rTMS. It should help improve the efficacy of rTMS in patients with medication-resistant AVH, and allow a better understanding of its neural impact. Here, we describe an exploratory study protocol which aims to identify structural and functional brain biomarkers associated with clinical response after an rTMS treatment for medication-resistant AVH in schizophrenia. METHODS: Forty-five schizophrenia patients with medication-resistant AVH will be enrolled in a double-blind randomized sham-controlled monocentric clinical trial. Patients will be assigned to a regime of 20 sessions of active or sham 1 Hz rTMS delivered twice a day, 5 days a week for 2 weeks over the left temporo-parietal junction. Response will be assessed after rTMS and patients will be classified in responders or non-responders to treatment. Magnetic resonance imaging (MRI) sessions including diffusion weighted imaging and resting-state functional MRI sequences will be recorded before the onset of the rTMS treatment and 3 days following its discontinuation. The primary outcome measure is difference in fractional anisotropy between responder and non-responder patients at baseline. Differences in resting-state functional MRI data at baseline will be also investigated between responder and non-responder groups. Clinical, neuropsychological, neurophysiological, and blood serum BDNF assessments will be performed at baseline, 3 days, 1 month, and 3 months following rTMS. DISCUSSION: The aim of this research project is to identify and assess the biomarker value of MRI-based structural and functional biomarkers predicting clinical response to rTMS for AVH in schizophrenia patients. The outcome of the trial should improve patient care by offering them a novel suitable therapy and deepen our understanding on how rTMS may impact AVH and develop more effective therapies adapted to individual patient needs. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02755623 . Registered on 22 April 2016.


Assuntos
Percepção Auditiva , Encéfalo/fisiopatologia , Alucinações , Esquizofrenia/terapia , Psicologia do Esquizofrênico , Estimulação Transcraniana por Corrente Contínua , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Mapeamento Encefálico/métodos , Fator Neurotrófico Derivado do Encéfalo/sangue , Imagem de Difusão por Ressonância Magnética , Método Duplo-Cego , Resistência a Medicamentos , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Esquizofrenia/sangue , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/fisiopatologia , Fatores de Tempo , Estimulação Transcraniana por Corrente Contínua/efeitos adversos , Resultado do Tratamento , Adulto Jovem
20.
Psychiatr Genet ; 29(4): 127-129, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30933047

RESUMO

Dysregulation of the immune system in mental disease, particularly complement component 4 (C4), which may be associated with schizophrenia, has been repeatedly observed. This study investigated the association between the level of serum component 4 and schizophrenia. Data were derived from a case-control association study of 40 unrelated adult patients with schizophrenia and 40 matched healthy controls. The component 4 level in serum was measured for comparative analysis by a component 4 enzyme-linked immunosorbent assay kit. Our findings suggest that the serum component 4 level is lower in patients with schizophrenia than in the controls, and the results apply to both males and females. Our results will lay an important foundation for establishing diagnostic methods and provide feasible and reliable evidence for the clinical treatment of schizophrenia.


Assuntos
Complemento C4/metabolismo , Esquizofrenia/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino
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