Effects of Risperidone on Cytokine Profile in Drug-Naive First-Episode Psychosis

Background: There is robust evidence that schizophrenia is characterized by immune-inflammatory abnormalities, including variations on cytokine levels. the results of previous studies, however, are heterogeneous due to several confounding factors, such as the effects of antipsychotic drugs. Therefore, research on drug-naive first-episode psychosis (FEP) patients is essential to elucidate the role of immune processes in that disorder.Methods: the aim of this study is to compare cytokine levels (IL-2, IL-10, IL-4, IL-6, IFN-gamma, TNF-alpha, and IL-17) in drug-naive FEP patients both before and after treatment with risperidone for 10 weeks, and to investigate possible associations between cytokine levels and clinical responses to treatment and presence of depressive symptoms. It this study, we included 55 drug-naive FEP patients who had repeated measurements of cytokine levels and 57 healthy controls.Results: We found that FEP patients had significantly higher IL-6, IL-10 and TNF-alpha levels than healthy controls. After risperidone treatment, these three cytokines and additionally IL-4 decreased significantly. No significant difference was found between the post-treatment cytokine levels in FEP patients and in healthy controls, suggesting that these alterations in cytokine profiles are a state marker of FEP. No significant association was found between risperidone-induced changes in cytokines and the clinical response to treatment or the presence of depression. There was a significant inverse association between the risperidone-induced changes in IL-10 and the negative symptoms.Conclusions: in conclusion, our results show a specific cytokine profile in FEP patients (monocytic and regulatory T-cell activation) and suggest immunoregulatory effects of risperidone treatment, characterized by suppressant effects on monocytic, Th2, and T-regulatory functions.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundacao SafraFundacao ABADSJanssenEli LillyLundbeckNovartisRocheUniversidade Federal de São Paulo, Dept Psychiat, São Paulo, BrazilFac Ciencias Med Santa Casa São Paulo, Episode Psychosis Program 1, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Morphol & Genet, Div Genet, São Paulo, BrazilDeakin Univ, Dept Psychiat, Geelong, Vic 3217, AustraliaChulalongkorn Univ, Dept Psychiat, Bangkok, ThailandUniversidade Federal de São Paulo, Dept Psychiat, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Morphol & Genet, Div Genet, São Paulo, BrazilWeb of Scienc

Catechol-O-methyltransferase (COMT) polymorphisms modulate working memory in individuals with schizophrenia and healthy controls

Objective: Cognitive impairment is a core feature of schizophrenia, related to dopaminergic dysfunction in the prefrontal cortex (PFC). It is hypothesized that functional single nucleotide polymorphism (SNP) rs4680 of the catechol-O-methyltransferase (COMT) gene could mediate the relationship between cognition and dopamine activity in the PFC. Other COMT SNPs could also play a role. Methods: We evaluated the role of three COMT SNPs (rs737865, rs165599, and rs4680) in schizophrenia and their impact on three working memory tasks. For genetic association analyses, 212 individuals with schizophrenia and 257 healthy controls (HCs) were selected. The Visual Working Memory (VWM) Task, Keep Track Task, and Letter Memory Task were administered to 133 schizophrenics and 93 HCs. Results: We found a significant association of rs737865, with the GG genotype exerting a protective effect and the GA haplotype (rs4680/rs165599) exerting a risk effect for schizophrenia. COMT rs4680 AA carriers and rs737865 AA carriers scored lowest on the Keep Track Task. When the genotype* group interaction effect was evaluated, rs165599 exerted opposite effects for VWM and Keep Track task performance in patients and controls, with AA carriers scoring lowest on both tests among controls, but highest among patients. Conclusion: These data support the hypothesis that COMT polymorphisms may be associated with schizophrenia and modulate cognition in patients and controls.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), BrazilUniv Fed Sao Paulo UNIFESP, Dept Psiquiatria, Sao Paulo, SP, BrazilFMABC, Dept Saude Colet, Santo Andre, SP, BrazilUniv Fed Sao Paulo, Lab Interdisciplinar Neurociencias Clin LiNC, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Morfol & Genet, Disciplina Genet, Sao Paulo, SP, BrazilCtr Univ Fundcao Inst Ensino Osasco UNIFIEO, Dept Psicol Educ, Osasco, SP, BrazilUniv Fed Sao Paulo, Dept Psicobiol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, Dept Psiquiatria, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Lab Interdisciplinar Neurociencias Clin LiNC, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Morfol & Genet, Disciplina Genet, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Psicobiol, Sao Paulo, SP, BrazilFAPESP: 2007/58736-1FAPESP: 2011/50740-5Web of Scienc

Gene expression analysis in blood of ultra-high risk subjects compared to first-episode of psychosis patients and controls

<div><p></p><p><i>Objectives.</i> This study aimed to investigate peripheral blood gene expression in ultra-high-risk subjects (UHR) compared to first-episode psychosis individuals (FEP) and healthy controls (HC). <i>Methods.</i> We enrolled 22 UHR, 66 FEP and 67 HC and investigated the expression of 12 genes using Taqman assays. We used the Univariate General Linear Model, as well as Bonferroni correction for multiple comparisons. <i>Results.</i> We found that <i>UFD1L</i> (ubiquitin fusion degradation 1 like (yeast)) gene was upregulated in UHR group compared to HC and FEP (<i>P = </i>3.44 × 10^–6 ; <i>P = </i>9.41 × 10^–6). <i>MBP</i> (myelin basic protein) was downregulated in UHR compared to FEP (<i>P = </i>6.07 × 10^–6). <i>DISC1</i> (disrupted in schizophrenia 1) was also upregulated in UHR compared to FEP but lost statistical significance when corrected for age. <i>Conclusions.</i> These genes are directly related to neurodevelopmental processes and have been associated to schizophrenia. Recent findings described that <i>DISC1</i> overexpression can disrupt <i>MBP</i> expression, thus, we think that these alterations in UHR individuals could be associated with a common process. <i>UFD1L</i> showed a different pattern of expression only for UHR group, suggesting that they can be under an acute endoplasmatic reticulum stress, demanding elevated levels of Ufd1. Further studies can improve knowledge on disease progression and putative targets to preventive strategies.</p></div

Prevalence of Cognitive Impairment Without Dementia and Dementia in Tremembe, Brazil

Made available in DSpace on 2019-09-12T16:53:51Z (GMT). No. of bitstreams: 0 Previous issue date: 2016Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Background:The prevalence of cognitive impairment is insufficiently determined in developing countries. The aim of this study was to ascertain the prevalence of cognitive impairment without dementia and dementia in community-dwelling elderly in Brazil.Methods:This was a single-phase cross-sectional survey of the elderly (aged 60 years and above) living in the municipality of Tremembe, Brazil. Twenty percent of the households with elderly persons were randomly selected from urban and rural areas, to obtain a homogenous representation of all socioeconomic and cultural levels.Results:We assessed 630 individuals [mean age, 71.3 y (7.99); mean years of education, 4.9 (+/- 4.54)] and found prevalence rates of 17.5% (95% confidence interval, 14.6-20.6) for dementia and 19.5% (95% confidence interval, 16.6-22.8) for cognitive impairment without dementia. These prevalence rates were influenced by age (P<0.001) and by educational level (P<0.001). There was no significant sex difference among diagnostic groups (P=0.166). The prevalence of dementia was higher in relatively younger individuals (below 70 y) when compared with other studies. Besides, dementia was associated with low socioeconomic status, stroke, previous psychiatric disorder, alcoholism, and epilepsy.Conclusions:The prevalence of dementia in this study was higher than in other studies, particularly among younger elderly.[Cesar, Karolina G.; Brucki, Sonia M. D.; Takada, Leonel T.; Oliveira, Maira O.; Porto, Fabio H. G.; Senaha, Mirna L. H.; Bahia, Valeria S.; Silva, Thais B. L.; Ianof, Jessica N.; Spindola, Livia; Schmidt, Magali T.; Jorge, Mario S.; Vale, Patricia H. F.; Cecchini, Mario A.; Cassimiro, Luciana; Soares, Roger T.; Goncalves, Marcia R.; Martins, Ana C. S.; Dare, Patricia; Smid, Jerusa; Porto, Claudia S.; Carthery-Goulart, Maria T.; Yassuda, Monica S.; Mansur, Leticia L.; Nitrini, Ricardo] Univ Sao Paulo, Dept Neurol, Cognit & Behav Neurol Unit, Sao Paulo, Brazil[Cesar, Karolina G.; Nascimento, Luiz F. C.; Gomes, Camila M. S.; Almeida, Milena C. S.] Universidade de Taubaté (Unitau