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1.
Artigo em Russo | MEDLINE | ID: mdl-34481435

RESUMO

OBJECTIVE: To identify relationships between thrombodynamic values and the severity of the condition in patients with schizophrenia spectrum disorders (SSD) before and after treatment. MATERIAL AND METHODS: The study included 92 patients in an acute state of schizophrenia or schizotypal disorder, aged 16 to 57 years (median age [Q1; Q3] - 25 years). All patients received complex psychopharmacotherapy adequate to their psychopathological state. The PANSS was used to assess the severity of symptoms in patients. The coagulation parameters were determined by the thrombodynamics test, in which the growth of fibrin clots in platelet free plasma are observed from special activator. The patient population was divided into two groups with weak and strong response to treatment. Data analysis included machine learning (ML) techniques: logistic regression, random forests, decision trees, support vector machines with radial basis functions, statistically weighted syndromes, permutation method. RESULTS: An analysis using permutation method revealed statistically significant different thrombodynamics values between groups of patients with weak and strong responses. There are significant differences between thrombodynamics values: T1D, T2D, T2Tlag and DTlag, and values characterizing the severity of positive symptoms before and after treatment (T1PposTot, T2PposTot), severity of psychopathological symptoms before treatment (T1Ppsy1, T1Ppsy6, T1Ppsy13). All ML techniques showed the relationship between thrombodynamics values and response to treatment. The best statistical significance was for statistically weighted syndromes method. CONCLUSION: The combination of the results of different ML techniques at a high level of statistical significance identifies the thrombodynamic predictors of weak effect of treatment of SSD.


Assuntos
Esquizofrenia , Coagulação Sanguínea , Plaquetas , Humanos , Aprendizado de Máquina , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico , Resultado do Tratamento
2.
Artigo em Russo | MEDLINE | ID: mdl-34481437

RESUMO

OBJECTIVE: To investigate whether visual processing abnormalities are the result of visual dysfunction involving cognitive impairment or independent abnormalities and to identify the relationship of visual impairments with cognitive functions and severity of psychopathological symptoms. MATERIAL AND METHODS: We compared results of visual size perception and actions on objects (motor assessment) in patients with schizophrenia (n=37), including patients with non-resistant schizophrenia (n=19) and healthy individuals (n=20). Cognitive impairments were assessed with BACS. Severity of schizophrenia symptoms was assessed with PANSS. RESULTS: The error in the visual size perception test was smaller in healthy controls compared with non-resistant patients (p<0.03). There are no significant differences between non-resistant patients and other groups. Also, there are no significant differences in motor assessment between healthy controls and patients with schizophrenia. In the visual size perception test, the amount of error correlates with cognitive impairments (r= -0.84, p<0.001), and the severity of psychotic symptoms on PANSS (r=0.55, p<0.05). CONCLUSION: Changes in visual threshold in patients with schizophrenia are correlated with cognitive dysfunction and reflect dysfunction in the parvocellular system.


Assuntos
Transtornos Cognitivos , Disfunção Cognitiva , Esquizofrenia , Cognição , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Humanos , Testes Neuropsicológicos , Esquizofrenia/complicações
3.
J Clin Psychiatry ; 82(5)2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34496461

RESUMO

Treatment-resistant schizophrenia (TRS) represents a major clinical challenge. The broad definition of TRS requires nonresponse to at least 2 sequential antipsychotic trials of sufficient dose, duration, and adherence. Several demographic, clinical, and neurologic predictors are associated with TRS. Primary (or early) TRS is present from the beginning of therapy, while patients with secondary (or later-onset) TRS initially respond to antipsychotics but become resistant over time, often after relapses. Guidelines worldwide recognize clozapine as the most effective treatment option for TRS, but clozapine is underused due to various barriers. Importantly, studies indicate that response rates are higher when clozapine is initiated earlier in the treatment course. Side effects are common with clozapine, particularly in the first few weeks, but can mostly be managed without discontinuation; they do require proactive assessment, intervention, and reassurance for patients. Furthermore, plasma leucocyte and granulocyte levels must be monitored weekly during the first 18-26 weeks of treatment, and regularly thereafter, according to country regulations. Therapeutic drug monitoring of clozapine trough plasma levels is helpful to guide dosing, with greatest efficacy at plasma clozapine levels ≥350 µg/L, although this level is not universal. Notably, plasma clozapine levels are generally greater at lower doses in nonsmokers, patients with heavy caffeine consumption, in women, in obese people, in those with inflammation (including COVID-19 infection), and in older individuals. Earlier and broader use of clozapine in patients with TRS is an important measure to improve outcomes of patients with this most severe form of the illness.


Assuntos
Antipsicóticos/administração & dosagem , Clozapina/administração & dosagem , Esquizofrenia/tratamento farmacológico , Antipsicóticos/efeitos adversos , Clozapina/efeitos adversos , Resistência a Medicamentos/efeitos dos fármacos , Tolerância a Medicamentos , Feminino , Humanos , Masculino
4.
Acta Biomed ; 92(4): e2021224, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34487088

RESUMO

Background and aim - Evidence on discrete dimensions underlining negative symptoms in First Episode Affective Psychosis (FEAP) may be useful for their treatment strategy, but is still relatively scarce. Aim of this study was to examine the negative symptom configuration in patients with FEAP using both exploratory and confirmatory factor analysis methods on the Positive And Negative Syndrome Scale (PANSS). Methods - Seventy-eight participants, aged 13-35 years, completed the PANSS within the "Parma Early Psychosis" (Pr-EP) program, a specialized protocol of early detection and intervention in psychosis implemented since January 2013 in all public adolescent and adult mental health services of the Parma Department of Mental Health (Northern Italy). Results - A 3-factor model (i.e. "Alogia", "Social Withdrawal" and "Motor/Affective Expression Poverty" domains) was identified. As an alternative, a 2-factor solution previously proposed in patients with first episode schizophrenia (always within the Pr-EP program) also showed good fit indices in our FEAP sample. Conclusions - Our results suggest the crucial importance of identifying discrete negative symptom domains already at the onset of affective psychosis in order to implement specific early intervention strategies aiming to improve prognosis and long-term outcomes also in this young FEAP help-seeking population.


Assuntos
Transtornos Psicóticos , Esquizofrenia , Adolescente , Diagnóstico Precoce , Seguimentos , Humanos , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/terapia , Esquizofrenia/diagnóstico , Esquizofrenia/terapia
5.
Nat Commun ; 12(1): 5276, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489429

RESUMO

A promise of genomics in precision medicine is to provide individualized genetic risk predictions. Polygenic risk scores (PRS), computed by aggregating effects from many genomic variants, have been developed as a useful tool in complex disease research. However, the application of PRS as a tool for predicting an individual's disease susceptibility in a clinical setting is challenging because PRS typically provide a relative measure of risk evaluated at the level of a group of people but not at individual level. Here, we introduce a machine-learning technique, Mondrian Cross-Conformal Prediction (MCCP), to estimate the confidence bounds of PRS-to-disease-risk prediction. MCCP can report disease status conditional probability value for each individual and give a prediction at a desired error level. Moreover, with a user-defined prediction error rate, MCCP can estimate the proportion of sample (coverage) with a correct prediction.


Assuntos
Predisposição Genética para Doença/genética , Aprendizado de Máquina , Herança Multifatorial/genética , Fatores Etários , Bancos de Espécimes Biológicos , Neoplasias da Mama/genética , Doença da Artéria Coronariana/genética , Diabetes Mellitus Tipo 2/genética , Feminino , Humanos , Doenças Inflamatórias Intestinais/genética , Masculino , Reprodutibilidade dos Testes , Esquizofrenia/genética , Suécia , Reino Unido
6.
BMC Psychiatry ; 21(1): 428, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465310

RESUMO

BACKGROUND: Accumulating evidence indicates that schizophrenia is accompanied by significant activation of the immune system; however, there is limited data from low and middle-income countries (LMIC). Inflammatory markers may be more relevant in LMIC settings where infectious conditions are more prevalent and may thus play some role in the causation and maintenance of schizophrenia. The aim of this study was to assess the level of inflammatory markers high sensitive C-reactive protein (hsCRP) and interleukin-6 (IL-6) in patients with schizophrenia. MATERIALS AND METHODS: The study population consisted of a total of 132 study participants; 82 participants with schizophrenia and 50 controls. hsCRP and IL-6 were measured using Cobas Integra 400 Plus and Cobas e 411 analysers respectively. RESULTS: The levels of hsCRP and IL-6 were significantly increased among participants with schizophrenia compared to controls: hsCRP mean value 2.87 ± 5.6 vs 0.67 ± 0.6 mg/L; IL-6 mean value 6.63 ± 5.6 vs 3.37 ± 4.0 pg/ml. Controlling for potential confounders (age, sex and body mass index), having a diagnosis of schizophrenia remained significantly associated with increased hsCRP and IL-6. CONCLUSION: The results confirm that inflammatory processes may have a role in the pathophysiology of schizophrenia regardless of setting. Despite failure of some interventions with anti-inflammatory properties, interventions to reduce inflammation are still worth pursuing.


Assuntos
Proteína C-Reativa , Esquizofrenia , Biomarcadores , Proteína C-Reativa/análise , Etiópia , Humanos , Inflamação , Interleucina-6
7.
Tijdschr Psychiatr ; 63(7): 499-508, 2021.
Artigo em Holandês | MEDLINE | ID: mdl-34523699

RESUMO

BACKGROUND: The Clozapine Plus Working Group is frequently consulted for advice on measures in case of infection with SARSCoV-2 and on vaccination against COVID-19 in patients receiving clozapine.

AIM: Inform about risks of infection with SARS-CoV-2 in patients with severe mental illness (SMI), patients with schizophrenia spectrum disorders (SSD), and patients treated with clozapine. Advise on monitoring of clozapine plasma levels and white blood cell count and differential in COVID-19 and after vaccination, as well as measures to be taken.

METHOD: Literature research and case studies.

RESULTS: SMI patients and in particular SSD patients have an increased risk of infection with SARS-CoV-2 with more hospitalizations and higher mortality than non-psychiatric patients. Patients using clozapine may be at greater risk of infection. SARS-CoV-2 infection may cause a dangerous increase of clozapine plasma levels and generally mild and short-term granulocytopenia and lymphocytopenia, which are usually not a result of clozapine treatment.

CONCLUSION: In case of COVID-19 extra alertness is required in patients with SMI and especially SSD. In clozapine users, in case of COVID-19, reduction in dose by half to three quarters of the original dose is recommended. When patients develop granulocytopenia, SARS-CoV-2 should be considered as the cause and not immediately clozapine. SMI patients and clozapine users in particular belong to a high risk group with a medical indication for early vaccination.


Assuntos
COVID-19 , Clozapina , Transtornos Mentais , Esquizofrenia , Clozapina/efeitos adversos , Humanos , SARS-CoV-2 , Esquizofrenia/tratamento farmacológico
8.
Tijdschr Psychiatr ; 63(7): 578-581, 2021.
Artigo em Holandês | MEDLINE | ID: mdl-34523711

RESUMO

Somatoparaphrenia is a disorder of body perception, usually on the left side. One or both limbs are seen as foreign or as belonging to somebody else. In the literature this rare phenomenon has been described in patients with brain damage, usually due to an infarction or other lesion to the right parietal lobe. We describe a patient with schizophrenia and addiction problems who believed that his left forearm was not his, but rather belonged to a Spanish girl. An EEG and an MRI of the brain showed no abnormalities. Despite years of antipsychotic treatment, the delusion persisted. To rule out neurological causes we recommend auxiliary investigations in all patients with somatoparaphrenia. No evidence-based treatments are known for this monothematic delusion in the context of schizophrenia.


Assuntos
Esquizofrenia , Braço , Encéfalo , Feminino , Humanos , Imageamento por Ressonância Magnética
9.
Nat Commun ; 12(1): 5251, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475392

RESUMO

DNA methylation (DNAm) is an epigenetic regulator of gene expression and a hallmark of gene-environment interaction. Using whole-genome bisulfite sequencing, we have surveyed DNAm in 344 samples of human postmortem brain tissue from neurotypical subjects and individuals with schizophrenia. We identify genetic influence on local methylation levels throughout the genome, both at CpG sites and CpH sites, with 86% of SNPs and 55% of CpGs being part of methylation quantitative trait loci (meQTLs). These associations can further be clustered into regions that are differentially methylated by a given SNP, highlighting the genes and regions with which these loci are epigenetically associated. These findings can be used to better characterize schizophrenia GWAS-identified variants as epigenetic risk variants. Regions differentially methylated by schizophrenia risk-SNPs explain much of the heritability associated with risk loci, despite covering only a fraction of the genomic space. We provide a comprehensive, single base resolution view of association between genetic variation and genomic methylation, and implicate schizophrenia GWAS-associated variants as influencing the epigenetic plasticity of the brain.


Assuntos
Metilação de DNA , Genoma Humano , Locos de Características Quantitativas/genética , Esquizofrenia/genética , Fatores Etários , Encéfalo/metabolismo , Encéfalo/patologia , Ilhas de CpG/genética , Epigênese Genética , Predisposição Genética para Doença/genética , Variação Genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único
10.
Sensors (Basel) ; 21(17)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34502815

RESUMO

Schizophrenia is a severe mental disorder that ranks among the leading causes of disability worldwide. However, many cases of schizophrenia remain untreated due to failure to diagnose, self-denial, and social stigma. With the advent of social media, individuals suffering from schizophrenia share their mental health problems and seek support and treatment options. Machine learning approaches are increasingly used for detecting schizophrenia from social media posts. This study aims to determine whether machine learning could be effectively used to detect signs of schizophrenia in social media users by analyzing their social media texts. To this end, we collected posts from the social media platform Reddit focusing on schizophrenia, along with non-mental health related posts (fitness, jokes, meditation, parenting, relationships, and teaching) for the control group. We extracted linguistic features and content topics from the posts. Using supervised machine learning, we classified posts belonging to schizophrenia and interpreted important features to identify linguistic markers of schizophrenia. We applied unsupervised clustering to the features to uncover a coherent semantic representation of words in schizophrenia. We identified significant differences in linguistic features and topics including increased use of third person plural pronouns and negative emotion words and symptom-related topics. We distinguished schizophrenic from control posts with an accuracy of 96%. Finally, we found that coherent semantic groups of words were the key to detecting schizophrenia. Our findings suggest that machine learning approaches could help us understand the linguistic characteristics of schizophrenia and identify schizophrenia or otherwise at-risk individuals using social media texts.


Assuntos
Esquizofrenia , Mídias Sociais , Humanos , Aprendizado de Máquina , Esquizofrenia/diagnóstico
11.
BMJ Case Rep ; 14(9)2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518181

RESUMO

Clozapine is an atypical antipsychotic used in refractory schizophrenia, also efficient in alleviating dyskinesia in Parkinson's disease. Despite its potency, this drug is associated with severe metabolic side effects, including increased risk for diabetes. We report the case of a 45-year-old overweight woman with Parkinson's disease who presented with rapid-onset hyperglycaemia within 2 months after starting clozapine for refractory dyskinaesia. She had a history of gestational diabetes. At presentation, her blood glucose level was 505 mg/dL and glycated haemoglobin 12.4%, with no catabolic symptoms. Clozapine was suspended and metformin was started, but adequate glycaemic control was achieved only with insulin therapy, along with exenatide and empagliflozin afterwards. We assume that clozapine acted as a trigger for rapid deterioration of glycaemic control through direct pathophysiological mechanisms, rather than an indirect slowly evolving weight gain-related metabolic syndrome pathway. Clinicians should be aware of this complication, enabling timely diagnosis and proper treatment.


Assuntos
Antipsicóticos , Clozapina , Hiperglicemia , Esquizofrenia , Antipsicóticos/efeitos adversos , Glicemia , Clozapina/efeitos adversos , Feminino , Humanos , Hiperglicemia/induzido quimicamente , Hiperglicemia/tratamento farmacológico , Pessoa de Meia-Idade , Esquizofrenia/tratamento farmacológico
12.
Int J Mol Sci ; 22(16)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34445065

RESUMO

Postmortem studies reveal that the brain pH in schizophrenia patients is lower than normal. The exact cause of this low pH is unclear, but increased lactate levels due to abnormal energy metabolism appear to be involved. Schizophrenia patients display distinct changes in mitochondria number, morphology, and function, and such changes promote anaerobic glycolysis, elevating lactate levels. pH can affect neuronal activity as H+ binds to numerous proteins in the nervous system and alters the structure and function of the bound proteins. There is growing evidence of pH change associated with cognition, emotion, and psychotic behaviors. Brain has delicate pH regulatory mechanisms to maintain normal pH in neurons/glia and extracellular fluid, and a change in these mechanisms can affect, or be affected by, neuronal activities associated with schizophrenia. In this review, we discuss the current understanding of the cause and effect of decreased brain pH in schizophrenia based on postmortem human brains, animal models, and cellular studies. The topic includes the factors causing decreased brain pH in schizophrenia, mitochondria dysfunction leading to altered energy metabolism, and pH effects on the pathophysiology of schizophrenia. We also review the acid/base transporters regulating pH in the nervous system and discuss the potential contribution of the major transporters, sodium hydrogen exchangers (NHEs), and sodium-coupled bicarbonate transporters (NCBTs), to schizophrenia.


Assuntos
Encéfalo/patologia , Esquizofrenia/patologia , Animais , Encéfalo/fisiopatologia , Química Encefálica , Humanos , Concentração de Íons de Hidrogênio , Esquizofrenia/fisiopatologia
13.
Int J Mol Sci ; 22(16)2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34445153

RESUMO

In order to achieve a desired therapeutic effect in schizophrenia patients and to maintain their mental wellbeing, pharmacological therapy needs to be continued for a long time, usually from the onset of symptoms and for the rest of the patients' lives. The aim of our present research is to find out the in vivo effect of chronic treatment with atypical neuroleptic iloperidone on the expression and activity of cytochrome P450 (CYP) in rat liver. Male Wistar rats received a once-daily intraperitoneal injection of iloperidone (1 mg/kg) for a period of two weeks. Twenty-four hours after the last dose, livers were excised to study cytochrome P450 expression (mRNA and protein) and activity, pituitaries were isolated to determine growth hormone-releasing hormone (GHRH), and blood was collected for measuring serum concentrations of hormones and interleukin. The results showed a broad spectrum of changes in the expression and activity of liver CYP enzymes, which are important for drug metabolism (CYP1A, CYP2B, CYP2C, and CYP3A) and xenobiotic toxicity (CYP2E1). Iloperidone decreased the expression and activity of CYP1A2, CP2B1/2, CYP2C11, and CYP3A1/2 enzymes but increased that of CYP2E1. The CYP2C6 enzyme remained unchanged. At the same time, the level of GHRH, GH, and corticosterone decreased while that of T3 increased, with no changes in IL-2 and IL-6. The presented results indicate neuroendocrine regulation of the investigated CYP enzymes during chronic iloperidone treatment and suggest a possibility of pharmacokinetic/metabolic interactions produced by the neuroleptic during prolonged combined treatment with drugs that are substrates of iloperidone-affected CYP enzymes.


Assuntos
Antipsicóticos/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Isoxazóis/farmacologia , Fígado/efeitos dos fármacos , Piperidinas/farmacologia , Animais , Antipsicóticos/administração & dosagem , Sistema Enzimático do Citocromo P-450/genética , Expressão Gênica/efeitos dos fármacos , Isoxazóis/administração & dosagem , Fígado/metabolismo , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Piperidinas/administração & dosagem , Ratos , Ratos Wistar , Esquizofrenia/tratamento farmacológico , Esquizofrenia/metabolismo
14.
Int J Mol Sci ; 22(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34445411

RESUMO

BACKGROUND: The present study investigated the role of proteins from the bromodomain and extra-terminal (BET) family in schizophrenia-like abnormalities in a neurodevelopmental model of schizophrenia induced by prenatal methylazoxymethanol (MAM) administration (MAM-E17). METHODS: An inhibitor of BET proteins, JQ1, was administered during adolescence on postnatal days (P) 23-P29, and behavioural responses (sensorimotor gating, recognition memory) and prefrontal cortical (mPFC) function (long-term potentiation (LTP), molecular and proteomic analyses) studies were performed in adult males and females. RESULTS: Deficits in sensorimotor gating and recognition memory were observed only in MAM-treated males. However, adolescent JQ1 treatment affected animals of both sexes in the control but not MAM-treated groups and reduced behavioural responses in both sexes. An electrophysiological study showed LTP impairments only in male MAM-treated animals, and JQ1 did not affect LTP in the mPFC. In contrast, MAM did not affect activity-dependent gene expression, but JQ1 altered gene expression in both sexes. A proteomic study revealed alterations in MAM-treated groups mainly in males, while JQ1 affected both sexes. CONCLUSIONS: MAM-induced schizophrenia-like abnormalities were observed only in males, while adolescent JQ1 treatment affected memory recognition and altered the molecular and proteomic landscape in the mPFC of both sexes. Thus, transient adolescent inhibition of the BET family might prompt permanent alterations in the mPFC.


Assuntos
Azepinas/administração & dosagem , Acetato de Metilazoximetanol/análogos & derivados , Córtex Pré-Frontal/crescimento & desenvolvimento , Esquizofrenia/fisiopatologia , Triazóis/administração & dosagem , Adolescente , Desenvolvimento do Adolescente/efeitos dos fármacos , Animais , Azepinas/farmacologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Humanos , Potenciação de Longa Duração/efeitos dos fármacos , Masculino , Acetato de Metilazoximetanol/toxicidade , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Proteômica , Ratos , Reconhecimento Psicológico/efeitos dos fármacos , Esquizofrenia/induzido quimicamente , Esquizofrenia/metabolismo , Caracteres Sexuais , Triazóis/farmacologia
15.
BMC Psychiatry ; 21(1): 388, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34348681

RESUMO

BACKGROUND: The mammalian target of rapamycin protein (mTOR) signaling pathway is involved in the pathogenesis of schizophrenia and the mechanism of extrapyramidal adverse reactions to antipsychotic drugs, which might be mediated by an mTOR-dependent autophagy impairment. This study aimed to examine the expression of mTOR pathway genes in patients with schizophrenia treated with olanzapine, which is considered an mTOR inhibitor and autophagy inducer. METHODS: Thirty-two patients with acute schizophrenia who had been treated with olanzapine for four weeks (average dose 14.24 ± 4.35 mg/d) and 32 healthy volunteers were recruited. Before and after olanzapine treatment, the Positive and Negative Syndrome Scale (PANSS) was used to evaluate the symptoms of patients with schizophrenia, and the mRNA expression levels of mTOR pathway-related genes, including MTOR, RICTOR, RAPTOR, and DEPTOR, were detected in fasting venous blood samples from all subjects using real-time quantitative PCR. RESULTS: The MTOR and RICTOR mRNA expression levels in patients with acute schizophrenia were significantly decreased compared with those of healthy controls and further significantly decreased after four weeks of olanzapine treatment. The DEPTOR mRNA expression levels in patients with acute schizophrenia were not significantly different from those of healthy controls but were significantly increased after treatment. The expression levels of the RAPTOR mRNA were not significantly different among the three groups. The pairwise correlations of MTOR, DEPTOR, RAPTOR, and RICTOR mRNA expression levels in patients with acute schizophrenia and healthy controls were significant. After olanzapine treatment, the correlations between the expression levels of the DEPTOR and MTOR mRNAs and between the DEPTOR and RICTOR mRNAs disappeared. CONCLUSIONS: Abnormalities in the mTOR pathway, especially DEPTOR and mTORC2, might play important roles in the autophagy mechanism underlying the pathophysiology of schizophrenia and effects of olanzapine treatment.


Assuntos
Esquizofrenia , Sirolimo , Serina-Treonina Quinases TOR , Autofagia , Proteínas Relacionadas à Autofagia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Olanzapina/uso terapêutico , RNA Mensageiro/genética , Proteína Companheira de mTOR Insensível à Rapamicina , Proteína Regulatória Associada a mTOR , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genética , Serina-Treonina Quinases TOR/genética
16.
Syst Rev ; 10(1): 214, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34340713

RESUMO

BACKGROUND: Antipsychotic drugs and especially the newer compounds are known to cause metabolic side effects. However, a comprehensive comparison of the different substances regarding their propensity to cause metabolic side effects in medium- to long-term treatment of schizophrenia is lacking. METHODS: We will conduct a systematic review and network meta-analysis (NMA). We will include randomized controlled trials (RCTs) in which participants received either placebo or an antipsychotic (i.e. placebo-controlled trials and head-to-head comparisons of drugs). We will include studies in individuals with schizophrenia or related disorders (such as schizophreniform or schizoaffective disorders) at any stage of the disease (acute episode; maintenance phase). We will include studies with a duration of more than 3 months (medium- to long-term treatment). The primary outcome will be the change in body weight. Secondary outcomes will be the further metabolic parameters: fastening glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides. We will search for eligible studies (independent of the publication status) in Cochrane Schizophrenia Group's Study-Based Register of Trials, which is compiled by regular searches in trial registries and multiple electronic databases from their inception onwards including MEDLINE, EMBASE and PsycINFO. Additionally, we will search previously published systematic reviews and websites of pharmaceutical companies for eligible studies. At least two reviewers will independently conduct the process of study selection and data extraction. We will use the Cochrane Risk of Bias 2 tool to evaluate the risk of bias in studies. We will conduct random-effects NMA within a Bayesian framework to synthesize all evidence for each outcome. We will conduct sensitivity and subgroup analyses to assess the robustness of the findings and to explore heterogeneity. The confidence in the results will be evaluated using the Confidence in Network Meta-Analysis (CINeMA) framework. DISCUSSION: This systematic review and network meta-analysis will provide a synthesis of the existing evidence from RCTs how antipsychotic drugs differ in terms of metabolic side effects during medium- to long-term treatment. The findings have the potential to influence the choice of antipsychotic medication made by individuals with schizophrenia and their physicians. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020175414.


Assuntos
Antipsicóticos , Transtornos Psicóticos , Esquizofrenia , Antipsicóticos/efeitos adversos , Humanos , Metanálise como Assunto , Metanálise em Rede , Transtornos Psicóticos/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Esquizofrenia/tratamento farmacológico , Revisões Sistemáticas como Assunto
17.
Front Public Health ; 9: 705397, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34368068

RESUMO

Background: Duration of untreated psychosis (DUP) is associated with outcome in psychotic disorders and influenced by contextual factors such as immigration. Here we aimed to investigate the effect of mental health literacy (MHL) on duration of untreated psychosis considering the influence of migration and education. Methods: A total of 269 participants who received their first adequate medical treatment for a psychotic disorder within the current or past year were included to the Thematically Organized Psychosis study in Oslo, Norway. Sociodemographic and clinical information was collected through systematic interviews. MHL was measured as "recognition of psychotic symptoms" and assessed by "The Attitudes and Beliefs about Mental Health Problems" schizophrenia version. Influence of education, migration and MHL on DUP was analyzed with hierarchical block-wise multiple regression analysis. Results: Recognition of psychotic symptoms explained a small but unique variance (2.3%) in DUP after the effects of other important predictors were controlled for. Longer DUP was also associated with less education, lower premorbid social, and academic functioning, a diagnosis within schizophrenia spectrum disorder, and earlier age of onset. The model explained 26% of variance in DUP. Migration after the age of six and length of education were associated with MHL but did not have a significant interaction with MHL in predicting DUP. Conclusions: MHL, measured as recognition of psychotic symptoms, has a small but significant independent effect on DUP. The effect of MHL was larger than years of education and migration history, and did not interact with either, in predicting DUP. This suggests that MHL is an independent factor in prevention strategies for early psychosis.


Assuntos
Letramento em Saúde , Transtornos Psicóticos , Esquizofrenia , Humanos , Saúde Mental , Transtornos Psicóticos/diagnóstico , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico
18.
Transl Psychiatry ; 11(1): 412, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34341337

RESUMO

Epigenetic dysregulation is thought to contribute to the etiology of schizophrenia (SZ), but the cell type-specificity of DNA methylation makes population-based epigenetic studies of SZ challenging. To train an SZ case-control classifier based on DNA methylation in blood, therefore, we focused on human genomic regions of systemic interindividual epigenetic variation (CoRSIVs), a subset of which are represented on the Illumina Human Methylation 450K (HM450) array. HM450 DNA methylation data on whole blood of 414 SZ cases and 433 non-psychiatric controls were used as training data for a classification algorithm with built-in feature selection, sparse partial least squares discriminate analysis (SPLS-DA); application of SPLS-DA to HM450 data has not been previously reported. Using the first two SPLS-DA dimensions we calculated a "risk distance" to identify individuals with the highest probability of SZ. The model was then evaluated on an independent HM450 data set on 353 SZ cases and 322 non-psychiatric controls. Our CoRSIV-based model classified 303 individuals as cases with a positive predictive value (PPV) of 80%, far surpassing the performance of a model based on polygenic risk score (PRS). Importantly, risk distance (based on CoRSIV methylation) was not associated with medication use, arguing against reverse causality. Risk distance and PRS were positively correlated (Pearson r = 0.28, P = 1.28 × 10-12), and mediational analysis suggested that genetic effects on SZ are partially mediated by altered methylation at CoRSIVs. Our results indicate two innate dimensions of SZ risk: one based on genetic, and the other on systemic epigenetic variants.


Assuntos
Metilação de DNA , Esquizofrenia , Estudos de Casos e Controles , Epigênese Genética , Humanos , Aprendizado de Máquina , Esquizofrenia/genética
19.
Medicina (Kaunas) ; 57(8)2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34441022

RESUMO

BACKGROUND AND OBJECTIVES: Clozapine is the only antipsychotic approved for treatment-resistant schizophrenia. Despite its superior efficacy profile as compared with other antipsychotics, clozapine remains underutilized. Clozapine monitoring systems clearly describe the proposed management of clozapine-induced neutropenia; however, no specific mention is made of how to interpret neutrophilic leukocytosis, despite that being a relatively frequent finding. Prescribers unfamiliar with this molecule may misjudge its clinical significance, potentially leading to untimely treatment interruption. Here, we systematically review the literature on the risk of neutrophilic leukocytosis during clozapine treatment, and describe eight additional cases among our patient cohort. MATERIALS AND METHODS: We performed a systematic review of the literature on PubMed and Embase using the PRISMA 2020 guidelines, and selected all original reports describing either (1) the prevalence of neutrophilic leukocytosis during clozapine treatment, or (2) the clinical significance of neutrophilic leukocytosis. We described eight additional cases of neutrophilic leukocytosis during clozapine treatment while attending an outpatient psychiatric clinic. RESULTS: Our research ultimately yielded the selection of 13 articles included in this systematic review. The case series highlighted the presence of stable and clinically unremarkable neutrophilia during a follow-up ranging from one to ten years. CONCLUSIONS: Existing evidence indicates that leukocytosis associated with clozapine treatment can be considered as an asymptomatic and benign condition, suggesting that no change in clozapine treatment is needed upon its detection.


Assuntos
Antipsicóticos , Clozapina , Esquizofrenia , Antipsicóticos/efeitos adversos , Clozapina/efeitos adversos , Humanos , Leucocitose/induzido quimicamente , Leucocitose/tratamento farmacológico , Prevalência , Esquizofrenia/tratamento farmacológico
20.
Ned Tijdschr Geneeskd ; 1652021 07 22.
Artigo em Holandês | MEDLINE | ID: mdl-34346605

RESUMO

OBJECTIVE: To compare the incidence of psychosis among migrants with the incidence among the native Dutch in Amsterdam, Gouda and Voorhout. DESIGN: We identified patients with a first treated episode of psychosis (ICD-10 codes F20-F33) in 2010-2013 as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. Information on the composition of the population made it possible to calculate incidence rates. METHOD: We analyzed the Incidence Rate Ratios (IRR) of psychosis among various ethnic groups compared to the native Dutch using a Poisson model. RESULTS: The standardized rates in Amsterdam were 55.3/ 100,000 person-years (py) for migrants and 24.9/ 100,000py for native Dutch. In Gouda and Voorhout, these rates were 28.5 en 20.0/ 100,000py. We found increased rates among Moroccan males of the first (IRR=4.07 [95%-CI: 1.76-9.42]) and second generation (IRR=6.48 [3.30-12.68]) in Amsterdam. In Gouda and Voorhout, we found increased rates both among Moroccan males (IRR=3.37 [1.17-9.74]) of the first generation and Moroccan females of the second generation (IRR=7.10 [2.79-18.06]). High rates were also found in Amsterdam for male migrants from Eastern Europe (IRR=4.52 [2.24-9.11]), migrants from sub-Saharan Africa (IRR=3.15 [1.68-5.91]) and first-generation migrants, both males and females, from Surinam and the Netherlands Antilles. We found a decreased incidence for Western migrants. CONCLUSION: We found an increased incidence of psychosis among non-Western migrants and in Amsterdam also among Eastern-European migrants. The variation by region of origin and destination generation, and gender suggests that this risk is strongly influenced by the societal context.


Assuntos
Transtornos Psicóticos , Esquizofrenia , Migrantes , Feminino , Humanos , Incidência , Masculino , Países Baixos/epidemiologia , Transtornos Psicóticos/epidemiologia , Esquizofrenia/epidemiologia
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