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1.
Lancet Psychiatry ; 7(1): 64-77, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31860457

RESUMO

BACKGROUND: Antipsychotic treatment is associated with metabolic disturbance. However, the degree to which metabolic alterations occur in treatment with different antipsychotics is unclear. Predictors of metabolic dysregulation are poorly understood and the association between metabolic change and change in psychopathology is uncertain. We aimed to compare and rank antipsychotics on the basis of their metabolic side-effects, identify physiological and demographic predictors of antipsychotic-induced metabolic dysregulation, and investigate the relationship between change in psychotic symptoms and change in metabolic parameters with antipsychotic treatment. METHODS: We searched MEDLINE, EMBASE, and PsycINFO from inception until June 30, 2019. We included blinded, randomised controlled trials comparing 18 antipsychotics and placebo in acute treatment of schizophrenia. We did frequentist random-effects network meta-analyses to investigate treatment-induced changes in body weight, BMI, total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, and glucose concentrations. We did meta-regressions to examine relationships between metabolic change and age, sex, ethnicity, baseline weight, and baseline metabolic parameter level. We examined the association between metabolic change and psychopathology change by estimating the correlation between symptom severity change and metabolic parameter change. FINDINGS: Of 6532 citations, we included 100 randomised controlled trials, including 25 952 patients. Median treatment duration was 6 weeks (IQR 6-8). Mean differences for weight gain compared with placebo ranged from -0·23 kg (95% CI -0·83 to 0·36) for haloperidol to 3·01 kg (1·78 to 4·24) for clozapine; for BMI from -0·25 kg/m2 (-0·68 to 0·17) for haloperidol to 1·07 kg/m2 (0·90 to 1·25) for olanzapine; for total-cholesterol from -0·09 mmol/L (-0·24 to 0·07) for cariprazine to 0·56 mmol/L (0·26-0·86) for clozapine; for LDL cholesterol from -0·13 mmol/L (-0.21 to -0·05) for cariprazine to 0·20 mmol/L (0·14 to 0·26) for olanzapine; for HDL cholesterol from 0·05 mmol/L (0·00 to 0·10) for brexpiprazole to -0·10 mmol/L (-0·33 to 0·14) for amisulpride; for triglycerides from -0·01 mmol/L (-0·10 to 0·08) for brexpiprazole to 0·98 mmol/L (0·48 to 1·49) for clozapine; for glucose from -0·29 mmol/L (-0·55 to -0·03) for lurasidone to 1·05 mmol/L (0·41 to 1·70) for clozapine. Greater increases in glucose were predicted by higher baseline weight (p=0·0015) and male sex (p=0·0082). Non-white ethnicity was associated with greater increases in total cholesterol (p=0·040) compared with white ethnicity. Improvements in symptom severity were associated with increases in weight (r=0·36, p=0·0021), BMI (r=0·84, p<0·0001), total-cholesterol (r=0·31, p=0·047), and LDL cholesterol (r=0·42, p=0·013), and decreases in HDL cholesterol (r=-0·35, p=0·035). INTERPRETATION: Marked differences exist between antipsychotics in terms of metabolic side-effects, with olanzapine and clozapine exhibiting the worst profiles and aripiprazole, brexpiprazole, cariprazine, lurasidone, and ziprasidone the most benign profiles. Increased baseline weight, male sex, and non-white ethnicity are predictors of susceptibility to antipsychotic-induced metabolic change, and improvements in psychopathology are associated with metabolic disturbance. Treatment guidelines should be updated to reflect our findings. However, the choice of antipsychotic should be made on an individual basis, considering the clinical circumstances and preferences of patients, carers, and clinicians. FUNDING: UK Medical Research Council, Wellcome Trust, National Institute for Health Research Oxford Health Biomedical Research Centre.


Assuntos
Antipsicóticos , Metabolismo dos Lipídeos/efeitos dos fármacos , Meta-Análise em Rede , Esquizofrenia , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Glicemia/efeitos dos fármacos , Índice de Massa Corporal , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Esquizofrenia/tratamento farmacológico , Esquizofrenia/fisiopatologia , Ganho de Peso/efeitos dos fármacos
2.
Medicine (Baltimore) ; 98(43): e17399, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651843

RESUMO

INTRODUCTION: Schizophrenia is one of the most severe mental disorders with a prevalence of about 1% and a leading cause of disability among young adults. Pharmacotherapy is the mainstay in the management of schizophrenia. However, even with the best of medication, several problems like refractoriness, negative symptoms, frequent relapses, and cognitive impairments persist. METHODS: This is a randomized-controlled clinical study including patients from an urban tertiary hospital and a semi-urban community center, with a between-group, repeated-measures, longitudinal design. This study will recruit 160 patients with DSM 5 diagnosis of schizophrenia who are on stable medication for a minimum of 6 weeks; they will be randomly assigned into 2 arms viz., yoga therapy (YT), and treatment-as-usual (TAU) with 80 patients in each arm. Participants will undergo Clinical, Laboratory, and Radiological assessments at baseline and at intervals of 1 month, 3 months, and 6 months from the baseline. It is hypothesized that yoga will improve psychopathology and emotion processing, increase serum brain derived neurotrophic factor (BDNF) and plasma oxytocin levels and effect changes in cerebral activation in areas of the brain associated with schizophrenia. DISCUSSION: This study aims to measure the efficacy of a Yoga-based intervention as an adjunct in patients with schizophrenia as well as the mechanisms of these effects. TRIAL REGISTRATION: Registered retrospectively with Clinical Trial Registry - India (CTRI) with registration number CTRI/2017/08/009219.


Assuntos
Plasticidade Neuronal , Esquizofrenia/fisiopatologia , Esquizofrenia/terapia , Psicologia do Esquizofrênico , Ioga/psicologia , Adolescente , Adulto , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Método Simples-Cego , Resultado do Tratamento , População Urbana , Adulto Jovem
3.
Psychiatr Danub ; 31(3): 355-357, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31596829

RESUMO

We aimed to compare processing speed (PS) and its subcomponents in schizophrenia (SC) and schizoaffective disorder (SA). Thirty-five patients were divided into two groups (SC=18; SA=17). PS tasks from the MATRICS Consensus Cognitive Battery Central/South America version were used. Additional PS subcomponents were analyzed (i.e., behavioral execution, response processing, and accuracy). SA obtained significant higher scores than SC in response processing, verbal fluency and the PS general domain. Our results indicate that PS is a potential cognitive marker to differentiate between SC and SA. Further research with larger samples must be conducted.


Assuntos
Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Transtornos Psicóticos/fisiopatologia , Transtornos Psicóticos/psicologia , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Transtornos Cognitivos/complicações , Humanos , Testes Neuropsicológicos , Projetos Piloto , Transtornos Psicóticos/complicações , Esquizofrenia/complicações
4.
Psychiatr Danub ; 31(Suppl 3): 608-612, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488799

RESUMO

Schizophrenic patients have traditionally suffered from high rates of cardiovascular disease and early mortality. NICE guidelines suggest that several physical health measures be monitored regularly in these patients, and particularly those on antipsychotic medication, which has a wide side-effect profile that may potentiate the risk of cardiovascular disease and other comorbidities. This general practice audit aimed to determine the rates of physical health monitoring in primary care in patients on antipsychotic medication for over a year for psychotic symptoms or schizophrenia. The search was conducted in three different general practices in March 2019, yielding 19, 8 and 30 patients respectively, with a total of 57 patients. This audit aims to record and analyse rates of monitoring of a range of physical health measures recommended by NICE guidelines over the past year. The results demonstrated that physical health monitoring was poor amongst all the practices audited, especially that of prolactin and waist circumference. We recommend that these rates of monitoring be improved, through implementing templates or the delivery of targeted education to general practitioners and nurses.


Assuntos
Antipsicóticos/efeitos adversos , Medicina Geral , Atenção Primária à Saúde , Transtornos Psicóticos/complicações , Transtornos Psicóticos/tratamento farmacológico , Esquizofrenia/complicações , Esquizofrenia/tratamento farmacológico , Antipsicóticos/administração & dosagem , Auditoria Clínica , Humanos , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/fisiopatologia
5.
Adv Exp Med Biol ; 1178: 25-38, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31493220

RESUMO

Schizophrenia is a severe and debilitating psychiatric disorder believed to have neurodevelopmental origins. Several studies have associated energy metabolism dysfunction with the disorder, mostly related to glycolysis alterations. Glucose is the obligatory energy substrate of the brain and glycolysis is the first step for its metabolism. This takes place predominantly in glial cells, astrocytes and oligodendrocytes, whereas neurons present a predominant oxidative profile. Thus, glial cells generate either lactate or pyruvate to neurons for ATP production. In addition, some aspects of schizophrenia may reflect an advanced aging phenotype with effects on various neural cell types at different stages of the disease. Given the role of glial cells in brain energy metabolism, the association of glycolysis dysfunction and the accelerated aging of neuronal cells in schizophrenia, studies focusing on those aspects can yield important insights into the causes and implications of the disorder. In turn, this may lead to novel therapeutic strategies for improved treatment of individuals suffering with this disorder.


Assuntos
Envelhecimento , Glicólise , Neuroglia , Esquizofrenia , Metabolismo Energético , Glucose/metabolismo , Humanos , Neuroglia/metabolismo , Fenótipo , Esquizofrenia/fisiopatologia
6.
Rev Invest Clin ; 71(4): 246-254, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31448785

RESUMO

Background: Schizophrenia (SCZ) and dementia, often related, are two of the most common neuropsychiatric diseases; epidemiological studies have shown that SCZ patients present a 2-fold increased risk for dementia compared to non-schizophrenic individuals. We explored the presence of rare and novel damaging gene variants in patients diagnosed with late-onset dementia of Alzheimer's type (DAT) or SCZ. Methods: We included 7 DAT and 12 SCZ patients and performed high-depth targeted sequencing of 184 genes. Results: We found novel and rare damaging variants in 18 genes in these Mexican patients. Carriers of these variants showed extreme phenotypes, including, treatment-resistant SCZ or cognitive decline. Furthermore, we found a variation on ABCC1 as a possible link between psychosis and cognitive impairment. Discussion: As an exploratory analysis, we report some interesting variations that should be corroborated in larger sample size studies.


Assuntos
Doença de Alzheimer/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Demência/fisiopatologia , Esquizofrenia/fisiopatologia , Doença de Alzheimer/genética , Disfunção Cognitiva/genética , Demência/genética , Variação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , México , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Fenótipo , Esquizofrenia/genética
7.
Australas Phys Eng Sci Med ; 42(3): 887-897, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31364088

RESUMO

Cognitive dysfunction is a core defect for schizophrenia subjects. This is due to structural and functional abnormalities of the brain which can be determined using Electroencephalogram (EEG). The objective of this study is to analyze EEG in patients with schizophrenia using power spectral density during mental activity. The subjects included in this study are 52 schizophrenia subjects and 29 Normal subjects. EEG is recorded under resting condition and during mental activity. Two modified odd ball paradigms are designed to stimulate mental activity and named as stimulus 1 and stimulus 2. EEG signal is filtered using FIR band pass filter to extract delta, theta, alpha, and beta band EEG. This method measures powers of each band using Welch power spectral density method called absolute power. The absolute power of alpha band is low and beta band is high for schizophrenia subjects compared to normal subjects during rest and two stimuli. Student's t-test is used to find the significant features (p < 0.05) at each recording condition. The significant features from each recording condition are used to classify Schizophrenia using both BPN and SVM classifier. SVM classifier is produced maximum sensitivity of 91% when features from all recording conditions are combined together. Thus this work concludes that the mental activity EEG supports for classifying Schizophrenia from normal and hence absolute band powers can be used as features to identify Schizophrenia.


Assuntos
Eletroencefalografia , Processos Mentais/fisiologia , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatologia , Adulto , Fontes de Energia Elétrica , Feminino , Humanos , Masculino , Processamento de Sinais Assistido por Computador , Máquina de Vetores de Suporte
8.
Behav Processes ; 167: 103936, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31381984

RESUMO

Reversal-learning impairments in the maternal immune activation (MIA) model of schizophrenia risk have been interpreted as being indicative of deficits in reinforcement learning. Here we sought to assess the specific role of cognitive burden in discrimination learning and reversal performance in this model. Control and MIA rats were trained on a visual discrimination task in which responses on either a left or right lever were rewarded depending on the location of a cue light at the beginning of the trial. Groups of MIA and control rats differed in the difficulty of the discrimination rule they initially learned (pressing the lever on the same side vs the opposite side of the cue light). Once the discrimination was learned, performance was tested across four reversals. Across all phases of the experiment, rats in Group Same performed better than rats in Group Opposite. There was no difference in performance of control and MIA rats during acquisition or baseline, but MIA rats displayed impaired performance across reversals, with performance decrements manifesting later in reversals after the new discrimination rule had been learnt. Across reversals, MIA rats also made more perseverative errors than control rats. These results are consistent with others that have shown reversal learning impairments in MIA rats. The results further suggest that impaired behavioural flexibility in the MIA model is not due to a deficit in reinforcement learning, but due to an impaired ability to organize information gained from experience into an accurate and stable representation of the current task requirements.


Assuntos
Cognição/fisiologia , Aprendizagem por Discriminação/fisiologia , Reversão de Aprendizagem/fisiologia , Esquizofrenia/fisiopatologia , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Recompensa , Percepção Visual/fisiologia
9.
EBioMedicine ; 45: 432-446, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31255657

RESUMO

BACKGROUND: Betaine is known to act against various biological stresses and its levels were reported to be decreased in schizophrenia patients. We aimed to test the role of betaine in schizophrenia pathophysiology, and to evaluate its potential as a novel psychotherapeutic. METHODS: Using Chdh (a gene for betaine synthesis)-deficient mice and betaine-supplemented inbred mice, we assessed the role of betaine in psychiatric pathophysiology, and its potential as a novel psychotherapeutic, by leveraging metabolomics, behavioral-, transcriptomics and DNA methylation analyses. FINDINGS: The Chdh-deficient mice revealed remnants of psychiatric behaviors along with schizophrenia-related molecular perturbations in the brain. Betaine supplementation elicited genetic background-dependent improvement in cognitive performance, and suppressed methamphetamine (MAP)-induced behavioral sensitization. Furthermore, betaine rectified the altered antioxidative and proinflammatory responses induced by MAP and in vitro phencyclidine (PCP) treatments. Betaine also showed a prophylactic effect on behavioral abnormality induced by PCP. Notably, betaine levels were decreased in the postmortem brains from schizophrenia, and a coexisting elevated carbonyl stress, a form of oxidative stress, demarcated a subset of schizophrenia with "betaine deficit-oxidative stress pathology". We revealed the decrease of betaine levels in glyoxylase 1 (GLO1)-deficient hiPSCs, which shows elevated carbonyl stress, and the efficacy of betaine in alleviating it, thus supporting a causal link between betaine and oxidative stress conditions. Furthermore, a CHDH variant, rs35518479, was identified as a cis-expression quantitative trait locus (QTL) for CHDH expression in postmortem brains from schizophrenia, allowing genotype-based stratification of schizophrenia patients for betaine efficacy. INTERPRETATION: The present study revealed the role of betaine in psychiatric pathophysiology and underscores the potential benefit of betaine in a subset of schizophrenia. FUND: This study was supported by the Strategic Research Program for Brain Sciences from AMED (Japan Agency for Medical Research and Development) under Grant Numbers JP18dm0107083 and JP19dm0107083 (TY), JP18dm0107129 (MM), JP18dm0107086 (YK), JP18dm0107107 (HY), JP18dm0107104 (AK) and JP19dm0107119 (KH), by the Grant-in-Aid for Scientific Research on Innovative Areas from the MEXT under Grant Numbers JP18H05435 (TY), JP18H05433 (AH.-T), JP18H05428 (AH.-T and TY), and JP16H06277 (HY), and by JSPS KAKENHI under Grant Number JP17H01574 (TY). In addition, this study was supported by the Collaborative Research Project of Brain Research Institute, Niigata University under Grant Numbers 2018-2809 (YK) and RIKEN Epigenetics Presidential Fund (100214-201801063606-340120) (TY).


Assuntos
Betaína/farmacologia , Colina Desidrogenase/genética , Psicotrópicos/farmacologia , Esquizofrenia/tratamento farmacológico , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Metilação de DNA/efeitos dos fármacos , Suplementos Nutricionais , Modelos Animais de Doenças , Genótipo , Humanos , Japão , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Metanfetamina/farmacologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Locos de Características Quantitativas , Esquizofrenia/genética , Esquizofrenia/fisiopatologia
10.
BMC Res Notes ; 12(1): 376, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31262359

RESUMO

OBJECTIVE: Drugs for managing mental disorders can cause adverse drug reactions (ADRs) that have negative impacts on patients yet, in Malawi, epidemiological data on the drug-related problems are limited. This study assessed the prevalence and severity of ADRs in out-patients at Zomba Mental Hospital. RESULTS: Twenty-six of forty patients (65.0%) were taking haloperidol and 14 (35.0%) chlorpromazine. The commonest diagnosis was schizophrenia (n = 23, 57.5%) followed by epileptic psychosis (n = 4, 10.0%) and general psychosis (n = 4, 10.0%) with one of psychotic depression and one psychosis secondary to general medical condition. Comorbidities were also found with epilepsy being the commonest (n = 4, 10.0%). All patients reported at least one ADR of varying severity (mild, moderate and severe). Polydipsia was the most prevalent (24, 60.0%) followed by weight gain (20, 50.0%), spasm (15, 37.5%) and xerostomia (15, 37.5%). Some ADRs were gender specific and these included impotence (6/27, 29.6%) for males and menstrual changes (3/14, 21.4%) for females. Severe ADRs were more common in the older aged group (> 35 years 8.3% vs 7.1%), in males (11.1% vs 0.0%) and on chlorpromazine (14.3% vs 3.8%). Patients taking chlorpromazine and haloperidol are at risk of experiencing a wide range of ADRs with varying degrees of severity.


Assuntos
Antipsicóticos/efeitos adversos , Clorpromazina/efeitos adversos , Disfunção Erétil/diagnóstico , Haloperidol/efeitos adversos , Distúrbios Menstruais/diagnóstico , Polidipsia/diagnóstico , Espasmo/diagnóstico , Xerostomia/diagnóstico , Adolescente , Adulto , Antipsicóticos/administração & dosagem , Clorpromazina/administração & dosagem , Estudos Transversais , Disfunção Erétil/etiologia , Disfunção Erétil/fisiopatologia , Feminino , Haloperidol/administração & dosagem , Hospitais Psiquiátricos , Humanos , Malaui , Masculino , Distúrbios Menstruais/etiologia , Distúrbios Menstruais/fisiopatologia , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Polidipsia/etiologia , Polidipsia/fisiopatologia , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/tratamento farmacológico , Esquizofrenia/fisiopatologia , Convulsões/tratamento farmacológico , Convulsões/fisiopatologia , Espasmo/etiologia , Espasmo/fisiopatologia , Ganho de Peso/efeitos dos fármacos , Xerostomia/etiologia , Xerostomia/fisiopatologia
11.
J Clin Nurs ; 28(19-20): 3582-3589, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31162884

RESUMO

AIMS AND OBJECTIVES: To test Zauszniewski's resourcefulness and quality of life theory in community-based patients with schizophrenia. The objectives were to: (a) examine the relationship among psychotic symptoms, resourcefulness and quality of life, and (b) explore the determinants of quality of life. BACKGROUND: According to Zauszniewski's resourcefulness and quality of life theory, for patients, the skills constituting resourcefulness should centre on helping oneself or the use of resources to achieve their health. While the significant associations between resourcefulness and quality of life have been consistently delineated in published research, little is known about resourcefulness in patients with schizophrenia. DESIGN: A cross-sectional study design was used in this study. METHODS: A total of 120 patients were recruited with convenience sampling who received home care service and community rehabilitation programme. The participants were assessed with the Brief Psychiatric Rating Scale, the Resourcefulness Scale and the World Health Organization Quality of Life Scale-BREF. The psychotic symptoms were rated by the researchers with structured face-to-face interviews. Resourcefulness and quality of life were assessed through self-reporting. STROBE checklist was followed. RESULTS: The data were analysed using one-way analysis of variance, t test, Pearson's correlation coefficients and stepwise multiple regression analysis. Results showed that employment status and psychotic symptoms were correlated with resourcefulness, while employment status, psychotic symptoms and resourcefulness were correlated with quality of life. Resourcefulness and psychotic symptoms were the determinants of quality of life. CONCLUSION: Patients with employment and less psychotic symptoms had greater resourcefulness. In addition, patients with employment, less psychotic symptoms and greater resourcefulness had better quality of life. RELEVANCE TO CLINICAL PRACTICE: Community rehabilitation programmes should include supported employment, symptom management and resourcefulness skills training to enhance patients' resourcefulness and quality of life.


Assuntos
Emprego/psicologia , Qualidade de Vida , Resiliência Psicológica , Esquizofrenia/fisiopatologia , Adulto , Estudos Transversais , Emprego/estatística & dados numéricos , Feminino , Humanos , Vida Independente , Masculino , Pessoa de Meia-Idade , Autorrelato
12.
J Abnorm Psychol ; 128(5): 415-422, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31192637

RESUMO

Successful execution of many behavioral goals relies on well-organized patterns of saccadic eye movements, and in complex tasks, these patterns can reveal the component processes underlying task performance. The present study examined the pattern of eye movements in a visual search task to provide evidence of attentional control impairments in people with schizophrenia (PSZ). We tested PSZ(N = 38) and nonpsychiatric control subjects (NCS, N = 35) in a task that was designed to stress top-down control by pitting task goals against bottom-up salience. Participants searched for either a low-contrast (nonsalient) or a high-contrast (salient) target among low- and high-contrast distractors. By examining fixations of the low- and high-contrast items, we evaluated the ability of PSZ and NCS to focus on low-salience targets and filter out high-salience distractors (or vice versa). When participants searched for a salient target, both groups successfully focused on relevant, high-contrast stimuli and filtered out target-mismatched, low-contrast stimuli. However, when searching for a nonsalient target, PSZ were impaired at efficiently suppressing high-contrast (salient) distractors. Specifically, PSZ were more likely than NCS to fixate and revisit salient distractors, and they dwelled on these items longer than did NCS. The results provide direct evidence that PSZ are impaired in their ability to utilize top-down goals to overcome the prepotent tendency to focus attention on irrelevant but highly salient information. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Atenção/fisiologia , Função Executiva/fisiologia , Desempenho Psicomotor/fisiologia , Movimentos Sacádicos/fisiologia , Esquizofrenia/fisiopatologia , Percepção Visual/fisiologia , Adulto , Medições dos Movimentos Oculares , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
PLoS One ; 14(5): e0217404, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31150442

RESUMO

Everyday speech is produced with an intricate timing pattern and rhythm. Speech units follow each other with short interleaving pauses, which can be either bridged by fillers (erm, ah) or empty. Through their syntactic positions, pauses connect to the thoughts expressed. We investigated whether disturbances of thought in schizophrenia are manifest in patterns at this level of linguistic organization, whether these are seen in first degree relatives (FDR) and how specific they are to formal thought disorder (FTD). Spontaneous speech from 15 participants without FTD (SZ-FTD), 15 with FTD (SZ+FTD), 15 FDRs and 15 neurotypical controls (NC) was obtained from a comic strip retelling task and rated for pauses subclassified by syntactic position and duration. SZ-FTD produced significantly more unfilled pauses than NC in utterance-initial positions and before embedded clauses. Unfilled pauses occurring within clausal units did not distinguish any groups. SZ-FTD also differed from SZ+FTD in producing significantly more pauses before embedded clauses. SZ+FTD differed from NC and FDR only in producing longer utterance-initial pauses. FDRs produced significantly fewer fillers than NC. Results reveal that the temporal organization of speech is an important window on disturbances of the thought process and how these relate to language.


Assuntos
Esquizofrenia/fisiopatologia , Fala/fisiologia , Adulto , Cognição/fisiologia , Feminino , Humanos , Linguagem , Masculino , Pessoa de Meia-Idade , Psicologia do Esquizofrênico
14.
Expert Opin Ther Pat ; 29(7): 497-507, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31242055

RESUMO

INTRODUCTION: Positive allosteric modulation of mGlu2 has attracted much interest as an alternative approach to classical orthosteric receptor activation. Two mGlu2 PAMS have advanced into the clinic. The results obtained in schizophrenia and MDD phase 2 clinical trials have tempered the high expectations put on selective mGlu2 receptor activation for treating these conditions; nevertheless, the search for novel therapeutic indications and novel chemotypes continues to be an active field of research. AREAS COVERED: 2013-2018 patent literature on mGlu2 receptor PAMs. EXPERT OPINION: After a decade of intensive research, the mGlu2 PAM field has seen a deceleration in the last five years. Negative phase 2 schizophrenia clinical trials with JNJ-40411813 and AZD8529 seem to have tempered the high expectations of the scientific community on the utility of mGlu2 PAMs for the treatment of schizophrenia. Nevertheless, novel therapeutic indications continue to be explored and AZD8529 is currently in a phase 2 study for smoking cessation. The advances in medicinal chemistry and in pharmacology, with novel indications such as epilepsy, have set the stage in the field of mGlu2 receptor PAMs. Ongoing preclinical and clinical studies will contribute to define their optimal therapeutic indication and potential to become novel therapeutic agents.


Assuntos
Indóis/uso terapêutico , Oxidiazóis/uso terapêutico , Piperidinas/uso terapêutico , Piridonas/uso terapêutico , Receptores de Glutamato Metabotrópico/efeitos dos fármacos , Regulação Alostérica/efeitos dos fármacos , Animais , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/fisiopatologia , Humanos , Indóis/farmacologia , Oxidiazóis/farmacologia , Patentes como Assunto , Piperidinas/farmacologia , Piridonas/farmacologia , Receptores de Glutamato Metabotrópico/metabolismo , Esquizofrenia/tratamento farmacológico , Esquizofrenia/fisiopatologia
15.
PLoS One ; 14(5): e0215023, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31071097

RESUMO

Functional magnetic resonance imaging (fMRI), electroencephalogram (EEG), and diffusion tensor imaging (DTI) recording have complementary spatiotemporal resolution limitations but can be powerful methods when used together to enable both functional and anatomical modeling, with each neuroimaging procedure used to maximum advantage. We recorded EEGs during event-related fMRI followed by DTI in 15 healthy volunteers and 12 patients with schizophrenia using an omission mismatch negativity (MMN) paradigm. Blood oxygenation level-dependent (BOLD) signal changes were calculated in a region of interest (ROI) analysis, and fractional anisotropy (FA) in the white matter fibers related to each area was compared between groups using tract-specific analysis. Patients with schizophrenia had reduced BOLD activity in the left middle temporal gyrus, and BOLD activity in the right insula and right parahippocampal gyrus significantly correlated with positive symptoms on the Positive and Negative Syndrome Scale (PANSS) and hostility subscores. BOLD activation of Heschl's gyri also correlated with the limbic system, including the insula. FA values in the left anterior cingulate cortex (ACC) significantly correlated with changes in the BOLD signal in the right superior temporal gyrus (STG), and FA values in the right ACC significantly correlated with PANSS scores. This is the first study to examine MMN using simultaneous fMRI, EEG, and DTI recording in patients with schizophrenia to investigate the potential implications of abnormalities in the ACC and limbic system, including the insula and parahippocampal gyrus, as well as the STG. Structural changes in the ACC during schizophrenia may represent part of the neural basis for the observed MMN deficits. The deficits seen in the feedback/feedforward connections between the prefrontal cortex and STG modulated by the ACC and insula may specifically contribute to impaired MMN generation and clinical manifestations.


Assuntos
Encéfalo/diagnóstico por imagem , Imagem de Tensor de Difusão , Eletroencefalografia , Imagem por Ressonância Magnética , Esquizofrenia/fisiopatologia , Estimulação Acústica , Adulto , Encéfalo/fisiologia , Mapeamento Encefálico , Estudos de Casos e Controles , Potenciais Evocados Auditivos/fisiologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Giro Para-Hipocampal/diagnóstico por imagem , Giro Para-Hipocampal/fisiologia , Esquizofrenia/diagnóstico , Adulto Jovem
16.
J Mol Neurosci ; 68(4): 658-666, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31054090

RESUMO

The study aimed to confirm the association of the schizophrenia genome-wide association study (GWAS) hit rs2514218 located near the DRD2 gene with the risk of the disease and to investigate the relationships between rs2514218 and schizophrenia-related clinical and neuroimaging phenotypes. Genotypes at the rs2514218 site were determined for 2148 schizophrenia spectrum patients and 1273 control subjects from the Russian population. In subsets of subjects, we assessed symptomatic dimensions using the Positive and Negative Syndrome Scale (n = 1651) and Temporal Experience of Pleasure Scale (n = 471). At the brain level, gray matter volumes in striatal structures and cortical thickness in the lateral prefrontal cortical regions were investigated (n = 97). Genotype frequencies did not differ between patients and controls. The allelic association analysis yielded a near-threshold p value (p = 0.054), the magnitude (OR = 0.90), and direction of the minor allele (T) effect being in accord with those in the schizophrenia GWAS. Also, patients homozygous for the risk allele C had more severe consummatory anhedonia and a thinner cortex than controls and patients carrying the T allele. The largest effect size of the genotype with diagnosis interaction was seen in the right pars opercularis area. The findings support the role of rs2514218 in schizophrenia risk and presentation and suggest rs2514218 has an influence on brain morphology and negative symptoms.


Assuntos
Anedonia , Polimorfismo de Nucleotídeo Único , Córtex Pré-Frontal/diagnóstico por imagem , Receptores de Dopamina D2/genética , Esquizofrenia/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/fisiopatologia
17.
J Abnorm Psychol ; 128(5): 423-430, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31058523

RESUMO

Cognitive mechanisms underlying auditory hallucinations (AH) in schizophrenia have been related to working memory (WM), although the formative mechanism is unknown. The phonological loop refers to subvocal rehearsals of information held online for supporting WM. As WM deficiency is frequent in schizophrenia, we hypothesized that AH and WM deficit share a common dysfunction in phonological loop operation, especially when it is taxed by ambiguous auditory and verbal associations. We developed an active phonological priming (APP) paradigm in which participants generated arbitrary verbal associations to pseudowords with ambiguous meaning. They were later asked to rate their familiarity to each pseudoword, a task that required subvocal evaluation of ambiguous auditory-verbal information. Factor and mediation analyses were used to test the hypothesis that WM, AH, and APP induced phonological bias toward perceiving ambiguous contents as familiar may share a common underlying mechanism. In 32 patients with schizophrenia (SZ) and 20 healthy controls (HC), SZ rated ambiguous pseudowords as significantly more familiar compared with HC (p = .006), indicating a proneness to APP-induced bias. This increased subjective bias to perceive ambiguous contents as familiar after APP significantly correlated with AH severity (p = .001) and mediated the relationship between WM and AH. Factor analysis demonstrated a common latent factor among WM, AH, and the bias induced by active priming to ambiguous contents. A heightened phonological loop priming to ambiguous contents appears to be mechanistically linked to WM deficits and AH in schizophrenia. These findings emphasize the importance of jointly addressing WM deficits and AH in clinical practice and research. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Associação , Alucinações/fisiopatologia , Memória de Curto Prazo/fisiologia , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/fisiopatologia , Percepção da Fala/fisiologia , Adulto , Feminino , Alucinações/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/complicações
18.
Int J Mol Sci ; 20(9)2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31071949

RESUMO

Individuals born preterm have higher rates of neurodevelopmental disorders such as schizophrenia, autistic spectrum, and attention deficit/hyperactivity disorders. These conditions are often sexually dimorphic and with different developmental trajectories. The etiology is likely multifactorial, however, infections both during pregnancy and in childhood have emerged as important risk factors. The association between sex- and age-dependent vulnerability to neuropsychiatric disorders has been suggested to relate to immune activation in the brain, including complex interactions between sex hormones, brain transcriptome, activation of glia cells, and cytokine production. Here, we will review sex-dependent effects on brain development, including glia cells, both under normal physiological conditions and following perinatal inflammation. Emphasis will be given to sex-dependent effects on brain regions which play a role in neuropsychiatric disorders and inflammatory reactions that may underlie early-life programming of neurobehavioral disturbances later in life.


Assuntos
Encéfalo/crescimento & desenvolvimento , Inflamação/fisiopatologia , Transtornos do Neurodesenvolvimento/fisiopatologia , Neuroglia/patologia , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Espectro Autista/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Humanos , Inflamação/diagnóstico por imagem , Nascimento Prematuro/fisiopatologia , Esquizofrenia/fisiopatologia , Caracteres Sexuais
20.
Eur Arch Psychiatry Clin Neurosci ; 269(5): 499-515, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31115660

RESUMO

Schizophrenia is a severe neuropsychiatric disease that is associated with neurobiological alterations in multiple brain regions and peripheral organs. Negative symptoms and cognitive deficits are present in about half of patients and are difficult to treat, leading to an unfavorable functional outcome. To investigate the impact of aerobic exercise on various neurobiological parameters, we conducted a narrative review. Add-on aerobic exercise was shown to be effective in improving negative and general symptoms, cognition, global functioning, and quality of life in schizophrenia patients. Based on findings in healthy individuals and animal models, this qualitative review gives an overview of different lines of evidence on how aerobic exercise impacts brain structure and function and molecular mechanisms in patients with schizophrenia and how its effects could be related to clinical and functional outcomes. Structural magnetic resonance imaging studies showed a volume increase in the hippocampus and cortical regions in schizophrenia patients and healthy controls after endurance training. However, results are inconsistent and individual risk factors may influence neuroplastic processes. Animal studies indicate that alterations in epigenetic mechanisms and synaptic plasticity are possible underlying mechanisms, but that differentiation of glial cells, angiogenesis, and possibly neurogenesis may also be involved. Clinical and animal studies also revealed effects of aerobic exercise on the hypothalamus-pituitary-adrenal axis, growth factors, and immune-related mechanisms. Some findings indicate effects on neurotransmitters and the endocannabinoid system. Further research is required to clarify how individual risk factors in schizophrenia patients mediate or moderate the neurobiological effects of exercise on brain and cognition. Altogether, aerobic exercise is a promising candidate in the search for pathophysiology-based add-on interventions in schizophrenia.


Assuntos
Encéfalo/diagnóstico por imagem , Terapia por Exercício/psicologia , Exercício/fisiologia , Qualidade de Vida , Esquizofrenia/terapia , Encéfalo/fisiopatologia , Exercício/psicologia , Humanos , Imagem por Ressonância Magnética , Plasticidade Neuronal/fisiologia , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/fisiopatologia
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