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O insight cognitivo ou clínico refere-se à capacidade de atribuição de sentido aos sintomas presentes em transtornos psicóticos, especialmente naqueles relacionados ao espectro da esquizofrenia. A Beck Cognitive Insight Scale (BCIS) foi desenvolvida com a finalidade de auxiliar o tratamento de pessoas com o insight comprometido. No entanto, este instrumento ainda não foi devidamente adaptado ao contexto brasileiro. Este estudo teve como objetivo fazer a adaptação transcultural da BCIS para o português do Brasil por meio da evidência de validade de conteúdo. Seis juízes avaliaram os itens desta escala quanto à clareza da linguagem, pertinência prática, relevância teórica e relação item-dimensão. A BCIS apresentou concordância satisfatória nos índices de validade de conteúdo e homogeneidade das respostas referente à análise da clareza da linguagem, pertinência prática e relevância teórica e concordância entre item-dimensão teórica, com reformulação de alguns itens. A retrotradução da escala recebeu aval positiva de uma das autoras originais. No entanto, ainda é necessária a verificação das propriedades psicométricas desta versão da BCIS.

To investigate the association between cytokine peripheral levels and the risk of cardiovascular disease in patients with schizophrenia and controls.A sample of 40 patients and 40 control subjects participated in the study. Psychiatric diagnosis was established following structured clinical assessment. The Framingham Score was used to assess cardiovascular risk (CVR). Serum levels of the cytokines IL-1β, IL-6, IL-8, IL-10, IL-12p70 and TNF-α were determined by cytometric bead array (CBA) technique, and the serum levels of IL-33, sST2, sTNFR1, sTNFR2, Leptin and Adiponectin by Enzyme-Linked Immunosorbent assay (ELISA).Patients with schizophrenia showed greater frequency of moderate CVR when compared with controls (p = 0.14). In addition, patients showed higher levels of sTNFR2 and Adiponectin compared to controls (p = 0.007 and p 0.001, respectively). Adiponectin and sTNFR2 were associated with CVR only in patients (p = 0.0002 and p = 0.033, respectively). In multivariate analysis controlling for socio-demographic and clinical confounders, illness duration (r = 0.492; p 0.002) and sTNFR2 (r = 0.665; p 0.004) were independent predictors of CVR.Our results reinforce the concept that patients with schizophrenia are at greater risk to develop cardiovascular diseases, and suggest that the associated chronic low-grade inflammation might play a role in this process.

Tardive dyskinesia is a syndrome defined by the emergence of hyperkinetic involuntary movements after the exposure to dopamine receptor antagonists, mainly antipsychotics and antiemetics. It involves two main clinical presentations: orofaciolingual and limb-truncal dyskinesias. There are several nonmodifiable (e.g., age, sex) and modifiable (e.g., dose and duration of exposure) risk factors for tardive dyskinesia. In this context, long-term use of dopamine antagonists should be avoided whenever possible to prevent the development of this condition. Once tardive dyskinesia develops, if the withdrawal of the antipsychotic is not possible, switching to another one with lower risk is recommended. VMAT2 inhibitors can also be used for symptomatic treatment.

This paper presents the C-ORAL-ESQ corpus project, which is dedicated to the study of the speech of individuals with schizophrenia. The main aim of the project is to investigate cognitive aspects of individuals with schizophrenia. This investigation is carried through the compilation of a spontaneous speech corpus and its study, which focuses mainly on the analysis of information structuring and its prosodic correlates. The paper informs about the environment and the setting of the sound file recordings, the medical and ethical criteria for the selection of the participants, the corpus aimed dimensions and the present stage of compilation, as well as its design and compilation criteria, which include attention to prosodic annotation, and metadata related to the participants’ characteristics. Additionally, the theory adopted for the study of information structure is summarized, focusing on those aspects that can better address cognitive processes of individuals with schizophrenia and their prosodic correlates. Finally, the perspectives for future studies and resource compilations are presented.

Aims: Recent findings suggest that cognitive impairment can be associated with inflammation and immune changes in schizophrenia. We aimed to study possible associations between cytokine levels and cognitive performance in a sample of patients with schizophrenia.Methods: Cognition was assessed with the brief assessment of cognition in schizophrenia in 63 clinically stable outpatients with schizophrenia. Blood was collected and cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, TNF-α, IFN-γ) were measured by cytometric bead array method. Psychopathological scales were also applied.Results: IL-6 correlated negatively with general cognitive performance (rho = -0.395, p = .017) and positively with antipsychotic dose (rho = 0.412, p = .004). Multiple regression analysis showed that cognitive performance is associated with age and antipsychotic dose (p = .000 and p = .033).Conclusion: The association between IL-6 levels and cognitive performance is dependent on age and antipsychotic dose.

This study aimed at evaluating changes in the renin-angiotensin system (RAS) in patients with schizophrenia in comparison with controls. Plasma levels of angiotensin-converting enzyme (ACE), ACE2, angiotensin (Ang)-(1-7) and Ang II were assessed in 25 patients with schizophrenia and 20 controls. Patients with schizophrenia presented decreased levels of ACE compared to controls [median (25th-75th percentiles) = 434.79 (341.15-524.02) vs. 508.49 (396.34-608.72); p 0.05]. No significant differences were found regarding ACE2, Ang-(1-7) and Ang II levels. There were no associations between the measured molecules and clinical parameters. Our results corroborate the hypothesis that the RAS is involved in the pathophysiology of schizophrenia.

Objectives to evaluate cannabinoid receptors (CBRs) expression on peripheral immune cells, i.e., blood monocytes, neutrophils, lymphocytes, and NK cells, and their relationship to a wide range of serum cytokine levels in subjects with schizophrenia and controls. Methods A sample of 55 people with chronic schizophrenia and 48 controls were enrolled in the study. The expression of the cannabinoid receptors CB1R and CB2R was evaluated in peripheral blood leukocytes by flow cytometry. Serum levels of cytokines/chemokines were simultaneously analyzed by cytometric bead array. Results We found higher expression of cannabinoid receptors on cells of the innate immune system in subjects with schizophrenia when compared with controls. Serum levels of interleukin-4 (IL-4), IL-6, IL-10, IL-17, interferon (IFN-γ), and (C-X-C motif) ligand 10/interferon gamma-induced protein 10 (CXCL10/IP10) were decreased, while levels of the chemokine (C-C motif) ligand 2/monocyte chemoattractant protein-1 (CCL2/MCP-1) were increased in the schizophrenia group in comparison with controls. Patients with schizophrenia showed simpler correlation network between cytokines and CBRs expression than controls. Conclusion Patients with schizophrenia showed increased CBRs expression in cells of the innate immune system and simpler correlation network between cytokines and CBRs expression when compared with controls. These results suggest a defective endocannabinoid system-mediated immunomodulation in patients with schizophrenia.

Objective Changes in immune system have been reported in schizophrenia. This study aimed to evaluate the involvement of IL-33, a member of the IL-1 cytokine family, in schizophrenia and its association with cognitive performance in these patients. Methods Forty patients with chronic schizophrenia and 40 healthy subjects participated in the study. Serum levels of IL-33 and sST2 (soluble form of the IL-33 receptor) were measured using enzyme-linked immunosorbent assay (ELISA). Patients were evaluated with the Brief Assessment of Cognition in Schizophrenia (BACS) and the Schizophrenia Cognition Rating Scale (SCoRS). Results Patients with schizophrenia and controls presented similar serum levels of IL-33 and sST2. Levels of both markers were positively correlated with cognitive performance in patients with schizophrenia. Conclusion We found a significant correlation between IL-33 and sST2 levels and cognition in schizophrenia. Our results might help in the understanding of how immune markers are associated with cognitive impairment in schizophrenia. It remains to be determined whether the association between IL-33/sST2 and cognition is restricted to patients with schizophrenia.

Deficits in neurocognition and social cognition play a critical role in the functional impairment of patients with schizophrenia. Increased oxidative stress has been evidenced in schizophrenia. Increased oxidative stress can affect neuronal function and lead to impairments in neurocognitive functions (especially working memory) and social cognition.To investigate deficits in neurocognition and social cognition and their potential association with oxidative stress biomarkers in schizophrenia.Eight-five clinically stable patients with schizophrenia and 75 controls were enrolled in this study. Neurocognition was evaluated through the Brief Assessment of Cognition in Schizophrenia (BACS). Social cognition was assessed through the Hinting Task - a test of theory of mind - and an emotion processing test, Facial Emotion Recognition Test (FERT-100). Oxidative stress was assessed by measuring serum levels of glutathione (GSH) and thiobarbituric acid reactive substances (TBARS).Patients had decreased serum levels of GSH (Z=3.56; p0.001) and increased TBARS (Z=5.51; P0.001) when compared with controls. TBARS levels are higher in patients using first generation antipsychotics. Higher serum levels of TBARS in patients were associated with poor performance in working memory test (r=-0.39; p=0.002), even when controlling for age and negative symptoms (Standard Beta: -0.36; CI= -2.52 a -13.71).The association between greater lipid peroxidation, as assessed by TBARS, and worse performance in working memory corroborates theoretical models of greater vulnerability of schizophrenia to oxidative stress.

A etiopatogênese da esquizofrenia é complexa e envolve a interação entre fatores genéticos e ambientais. Alterações no sistema imune vêm sendo apontadas como possíveis participantes na fisiopatologia da esquizofrenia. Neste artigo, apresentamos uma revisão narrativa sobre as alterações imunes na fisiopatologia da esquizofrenia e o potencial de moléculas e/ou mecanismos do sistema imune serem biomarcadores e/ou alvos terapêuticos. Enquanto alguns estudos observam maior participação de citocinas da resposta imune do tipo células T auxiliares (Th1), interferon-gama (IFN-γ), interleucina 2 (IL-2) e fator de necrose tumoral-alfa (TNF-α), outros observam maior participação das citocinas IL-4, IL-6 e IL-10, pertencentes à reposta imune tipo Th2. A infecção pelo protozoário Toxoplasma gondii tem sido apontada como fator de risco para esquizofrenia, e uma possível explicação seria o desvio no metabolismo do triptofano, com consequente aumento de quinureninas, causado pela resposta inflamatória frente à presença do parasita. Ensaios clínicos têm sido realizados utilizando anti-inflamatórios como adjuvantes ao tratamento antipsicótico. Resultados promissores, como redução da sintomatologia negativa e melhora cognitiva, foram observados. O uso de antiinflamatórios com consequente melhora clínica reforçam a ideia da participação de componentes imunes/inflamatórios na fisiopatologia da esquizofrenia.

Cognitive assessment in schizophrenia has traditionally used batteries that are long and complex or differ widely in their content. The Brief Assessment of Cognition in Schizophrenia (BACS) has been developed to cover the main cognitive deficits of schizophrenia as well as to be easily and briefly administered, portable, sensitive and reliable. Objectives: To investigate the applicability and sensitivity of the Brazilian Version of the BACS (Brazilian-BACS). Methods: Performance of 20 stable patients with schizophrenia on the Brazilian-BACS was compared to 20 matched healthy controls. Results: Applying the Brazilian-BACS required 43.4±8.4 minutes for patients and 40.5±5.7 minutes for controls (p=0.17). All tests demonstrated significant differences between controls and patients (P

Background Cognition is a major determinant of functioning in patients with schizophrenia. There is evidence that the endocannabinoid system influences cognition in human subjects, and participates in the pathophysiology of schizophrenia. In a previous study, we have shown that the expression of cannabinoid receptors (CB1R and CB2R) on peripheral lymphocytes is inversely correlated with performance in the Brief Assessment of Cognition in Schizophrenia (BACS), in patients with schizophrenia. Recently, CBRs polymorphisms have been associated with an increased risk for schizophrenia, structural changes in the central nervous systems and in cognitive performance of the patients. The aim of the present study was to investigate the association between CBRs polymorphisms and cognitive performance as assessed by the BACS. Methods A sample of 85 stable medicated patients (61% men; age = 41.6 ± 12.2 years; illness duration = 12.8 ± 10.7 years) was enrolled in this study. Two CB1R polymorphisms (rs1049353; rs12720071) and one CB2R polymorphism (rs2229579) were tested. Results We did not find any difference in general cognitive performance (BACS total score) regarding the three polymorphisms tested. However, when we analysed specific cognitive domains we have found a significant difference (p=0.002) regarding working memory (assessed by the Digit Span test) in patients with the rs12720071 polymorphism, where those with allele C performed better than those with T/T genotype. Since about a third of the patients (34%) had a history of past use of cannabis and 2.5% reported current use, we performed the rs12720071 polymorphism analysis excluding these patients. In this subgroup of patients, those with allele C also performed significantly better on Digit Span test (p=0.037). Discussion In this sample, the rs12720071 polymorphism of CB1R appears to influence performance on a working memory task that is sensitive to prefrontal cortex function.

Purpose The purpose of this study was to test the psychometric properties of the Neurobehavior Inventory (NBI) in a group of temporal lobe epilepsy (TLE) patients from a tertiary care center, correlating its scores with the presence of psychiatric symptoms. Methods Clinical and sociodemographic data from ninety-six TLE outpatients were collected, and a neuropsychiatric evaluation was performed with the following instruments: Mini-Mental State Examination (MMSE), structured psychiatric interview (MINI-PLUS), Neurobehavior Inventory (NBI), and Hamilton Depression Rating Scale (HAM-D). Results Some traits evaluated by the NBI showed adequate internal consistency (mean inter-item correlation between 0.2 and 0.4) and were frequent, such as religiosity (74%) and repetitiveness (60.4%). Principal component analysis showed three factors, named here as emotions (Factor 1), hyposexuality (Factor 2), and unusual ideas (Factor 3). Depressive symptoms on HAM-D showed a strong association with emotions and hyposexuality factors. When patients with left TLE and right TLE were compared, the former exhibited more sadness (p = 0.017), and the latter, a greater tendency toward sense of personal destiny (p = 0.028). Conclusion Depression influences NBI scoring, mainly emotionality and hyposexuality traits. Neurobehavior Inventory subscales can be better interpreted with an appropriate evaluation of comorbid mood and anxiety disorders. Compromise in left temporal mesial structures is associated with increased tendency toward sad affect, whereas right temporal pathology is associated with increased beliefs in personal destiny.

BACKGROUND: Despite the old Kraepelinean concept that bipolar disorder (BD) does not evolve with cognitive decline, the presence of cognitive impairment, especially executive dysfunction has been recognized in BD patients. Brain-derived neurotrophic factor (BDNF) and pro-inflammatory molecules are important contributors to the pathophysiology of BD, and imbalance in peripheral levels of these molecules may be implicated in the cognitive decline observed in BD patients. We aimed to investigate the executive performance of BD type I euthymic patients and its relation with the plasma levels of BDNF, TNF-α and its related soluble receptors (sTNFR1 and sTNFR2). METHODS: We evaluated executive functioning through the Frontal Assessment Battery (FAB). Plasma levels of BDNF, TNF-α, sTNFR1 and sTNFR2 were measured using enzyme-linked immunosorbent assay (ELISA) in 25 euthymic type I BD patients and 25 age and gender matched healthy controls. RESULTS: BD patients had an impairment in executive functioning (p

Objective The aim of the work described here was to measure the role of psychopathological features, specifically impulsivity and depression, in suicidality in patients with temporal lobe epilepsy (TLE). Methods Neuropsychiatric evaluation of 66 outpatients with TLE was performed with the following instruments: a structured clinical interview (Mini International Neuropsychiatric Interview Plus), the Barratt Impulsiveness Scale, the Hamilton Anxiety Scale, the Beck Depression Inventory, and the Brief Psychiatric Rating Scale. Results A current Axis I psychiatric diagnosis, mainly mood and anxiety disorders, was assigned to 37 subjects (56.1%) Presence of suicide risk was identified in 19 patients (28.8%), and 14 (21.2%) had attempted suicide. Frequency of seizures ( P = 0.012), current major depression ( P = 0.001), and motor impulsivity ( P = 0.005) were associated with suicide risk on univariate analysis. Logistic regression stressed the main relevance of major depression (OR = 12.82, 95% CI = 2.58–63.76, P = 0.002) and motor impulsivity (OR = 1.21, 95% CI = 1.06–1.38, P = 0.005) to suicide risk. Conclusion Depression has a major influence on suicidality in epilepsy. Motor impulsivity is also relevant and may be an important component of depression in TLE associated with suicide risk.

OBJECTIVE: The Rey Auditory-Verbal Learning Test, which is used to evaluate learning and memory, is a widely recognized tool in the general literature on neuropsychology. This paper aims at presenting the performance of Brazilian adult subjects on the Rey Auditory-Verbal Learning Test, and was written after we published a previous study on the performance of Brazilian elderly subjects on this same test. METHOD: A version of the test, featuring a list of high-frequency one-syllable and two-syllable concrete Portuguese substantives, was developed. Two hundred and forty-three (243) subjects from both genders were allocated to 6 different age groups (20-24; 25-29; 30-34; 35-44; 45-54 and 55-60 years old). They were then tested using the Rey Auditory-Verbal Learning Test. RESULTS: Performance on the Rey Auditory-Verbal Learning Test showed a positive correlation with educational level and a negative correlation with age. Women performed significantly better than men. When applied across similar age ranges, our results were similar to those recorded for the English version of the Rey Auditory-Verbal Learning Test. CONCLUSION: Our results suggest that the adaptation of the Rey Auditory-Verbal Learning Test to Brazilian Portuguese is appropriate and that it is applicable to Brazilian subjects for memory capacity evaluation purposes and across similar age groups and educational levels.

OBJETIVO: Determinar os pontos de melhor sensibilidade e especificidade do Inventário de Depressão de Beck (BDI) e da Escala de Avaliação de Depressão de Hamilton (HAM-D) no diagnóstico de depressão associada à epilepsia. MÉTODOS: Setenta e três pacientes de um centro de referência no tratamento da epilepsia foram submetidos à avaliação neuropsiquiátrica. Foram colhidos dados clínicos e sociodemográficos, sendo utilizados os seguintes instrumentos: entrevista clínica estruturada (MINI-PLUS) para diagnóstico psiquiátrico conforme o DSM-IV, HAM-D e BDI. RESULTADOS: No momento da entrevista, 27,4% dos pacientes estavam deprimidos e 37% preenchiam critérios para diagnóstico de depressão maior ao longo da vida. A análise da curva ROC indicou que o ponto de corte em 16 (> 16) para o BDI (sensibilidade de 94,4%, especificidade de 90,6%) e em 16 (> 16) para a HAM-D (sensibilidade de 95%, especificidade de 75,5%) representou dicotomização ótima entre deprimidos e não deprimidos. Ambos os instrumentos apresentaram um valor preditivo negativo superior a 95%. CONCLUSÃO: A frequência de depressão maior é elevada em pacientes com epilepsia. BDI e a HAM-D podem auxiliar o clínico na identificação da depressão associada à epilepsia, diminuindo seu subdiagnóstico. OBJECTIVE: To determine cutoff points of highest sensitivity and specificity on the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HAM-D) for depression diagnosis in epilepsy. METHODS: Seventy-three patients from a referral center for the treatment of epilepsy underwent neuropsychiatric evaluation. We collected clinical and socio-demographic data, and applied the following instruments: Structured Clinical Interview (MINI-PLUS) for psychiatric diagnosis according to DSM-IV, HAM-D and BDI. RESULTS: At assessment, 27.4% of the patients were depressed and 37% met diagnostic criteria for lifetime major depression. The ROC curve analysis indicated that a score > 16 on the BDI (94.4% sensitivity, 90.6% specificity) and > 16 on the HAM-D (95% sensitivity, 75.5% specificity) revealed great dichotomy between depressed and nondepressed patients. Both instruments showed a negative predictive value exceeding 95%. CONCLUSION: The frequency of major depression is elevated in patients with epilepsy. BDI and HAM-D can help physicians in the identification of depression in epilepsy, reducing its underdiagnosis.

Contexto: O transtorno bipolar tipo I está comumente associado a comorbidades clínicas e psiquiátricas, mas ainda há poucos dados disponíveis sobre pacientes brasileiros. Objetivos: O objetivo do presente estudo foi avaliar a prevalência de comorbidades clínicas e psiquiátricas em uma amostra brasileira de pacientes bipolares tipo I. O objetivo secundário foi investigar as associações de características clínico-demográficas e comorbidades com tentativas de suicídio. Métodos: Foram incluídos neste estudo 94 pacientes bipolares tipo I. O diagnóstico psiquiátrico foi determinado utilizando-se a avaliação Mini International Neuropsychiatric Interview (MINI-Plus). O diagnóstico de comorbidades clínicas foi baseado na história clínica e no acompanhamento de clínicos gerais. Resultados: As comorbidades mais prevalentes nos pacientes bipolares foram: transtorno de ansiedade generalizada (19,20%), dependência de substâncias (43,60%), hipertensão arterial (29,80%), diabetes mellitus (17,00%), dislipidemia (22,30%) e hipotireoidismo (19,10%). Não foram encontradas diferenças estatísticas em relação às características demográficas ou à prevalência de comorbidades nos grupos com e sem tentativa de suicídio. Conclusão: Pacientes bipolares atendidos em serviço psiquiátrico apresentam elevada prevalência de comorbidades psiquiátricas e clínicas. Nessa população, tentativas de suicídio não se associam com a presença de comorbidades ou características demográficas.

A complex and dynamic environment where impulsivity probably interferes in the human behavior is the sport context. The aim of this exploratory study was to investigate the possible relationship between impulsivity and technical performance in handball athletes. Eleven junior female athletes on a handball team were submitted to a neuropsychological assessment of impulsivity using Conner’s CPT-II and the Iowa Gambling Task. In 11 matches, participants’ handball performance was analyzed. We adopted the resampling statistical approach to correlate the measures of technical performance with the neuropsychological measures. IGT net score was posi- tively correlated with technical faults. Omission errors on the CPT-II were positively correlated with the number of fouls suffered, the number of fouls committed, and the number of offensive fouls. Commission errors on the CPT-II were negatively correlated with rebounds with defense ball possession. Our results support the idea of relationships between impulsivity and technical performance in specific match situations.

INTRODUÇÃO: A preservação das habilidades de compreensão da fala nos idosos está correlacionada com a preservação das funções cognitivas. Essa habilidade é característica fundamental para a comunicação e sua avaliação possibilita a identificação de déficits cognitivos mais específicos, além de facilitar o desenvolvimento de estratégias de intervenção mais precoces e eficientes. OBJETIVO: Disponibilizar normas contemporâneas para a utilização de um instrumento de avaliação da compreensão verbal, o Token Test, para idosos brasileiros saudáveis. MÉTODO: Uma amostra com 120 idosos (76 mulheres), com médias de 71,1 anos para idade e de 6,9 anos de educação formal para escolaridade, foi avaliada utilizando o Miniexame do Estado Mental, para identificação da existência de comprometimento cognitivo, e o Token Test, para avaliação da compreensão da fala. RESULTADOS: Foram encontradas correlações significativas (p < 0,01) entre o escore do Token Test e a educação formal e a idade, os quais corresponderam respectivamente a 5% e 21% da variância compartilhada. Tais variáveis foram consideradas nas tabelas normativas. CONCLUSÃO:Nossos dados indicam que as normas disponibilizadas aqui são suficientemente representativas. Este trabalho abre caminho para estudos futuros de comparação entre o desempenho no Token Test de idosos saudáveis e daqueles em processos de declínio cognitivo. INTRODUCTION: The preservation of oral comprehension in the elderly is correlated with the preservation of their cognitive functions. Oral comprehension is a key feature for communication and its evaluation allows for the identification of more specific cognitive deficits, in addition to facilitating the development of more effective, early intervention strategies. OBJECTIVE: Provide contemporary standards for the use of an instrument to assess oral comprehension, the Token Test, in a sample of healthy seniors. METHOD: A sample of 120 patients (76 women) with mean age of 71.1 years and 6.9 years of formal education, was assessed using the Mini Mental State Examination to identify the existence of cognitive impairment, and the Token Test to assess oral comprehension. RESULTS: There were significant correlations (p < 0.01) between the token test scores for education and age, which accounted for 5% and 21% of shared variance, respectively. These two variables were considered on the normative data tables. DISCUSSION: The data obtained indicate that the standards provided here are sufficiently representative. This study identifies the need for future studies comparing the Token Test performance in elderly people either healthy or in the process of cognitive decline.

Objective The purpose of this research was to evaluate the Brazilian-Portuguese version of the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and to assess its psychometric properties. Methods This study involved 98 outpatients who underwent psychopathological evaluation with the Mini International Neuropsychiatric Interview—Plus Version, Hamilton Depression Scale (HAM-D), and a Portuguese version of the NDDI-E. Results The NDDI-E was easily understood and quickly administered to most of the patients. At a cutoff score > 15, NDDI-E had a sensitivity of 81.5%, a specificity of 83.1%, and a negative predictive value of 92.2% for diagnosis of major depression. Internal consistency reliability of the NDDI-E was 0.79, and there was also a positive correlation between the NDDI-E and the HAM-D (P Conclusion The Brazilian-Portuguese version of NDDI-E can be used as a practical screening tool to improve recognition of depression in Brazilian people with epilepsy.

CONTEXTO: A Qualidade de Vida (QV) constitui valiosa forma de avaliação do impacto de doenças na vida diária e favorece intervenções mais efetivas sob uma perspectiva biopsicossocial. OBJETIVOS: Este artigo procura analisar criticamente os dados disponíveis sobre as relações entre QV e cognição na esquizofrenia. MÉTODOS: Foi realizada uma pesquisa na base de dados PubMed e Lilacs com os descritores de assunto "schizophrenia" e "cognition disorder" ou "cognition" e "quality of life" ou "outcome assessment". RESULTADOS: Dos 27 artigos selecionados que estudavam a relação entre cognição e QV medida por meio de escalas, 20 mostraram associações. Essas foram mais importantes nos estudos que utilizaram escalas de QV administrada por pesquisador, em comparação com escalas de autoavaliação. CONCLUSÃO: A associação entre cognição e QV é mais evidente nos estudos que utilizaram medidas de QV feitas por pesquisadores do que naqueles que utilizaram autoavaliações. A avaliação cognitiva é importante não somente como parâmetro determinante de QV dos pacientes, mas também auxilia na interpretação das escalas de QV, sendo as autoavaliações mais adequadas em pacientes com menor prejuízo cognitivo. BACKGROUND: The Quality of Life (QoL) is a valuable way of assessing the impact of diseases in daily life and favors more effective interventions under a biopsychosocial perspective. OBJECTIVES: This article aimed to critically analyze the available data on the relationship between QoL and cognitive function in schizophrenia. METHODS: We performed a search in PubMed and Lilacs databases with the terms "schizophrenia" and "cognition disorder" or "cognition" and "quality of life" or "outcome assessment". RESULTS: From the 27 selected articles that studied the relationship between cognition and QoL measured by scales, 20 articles showed associations. The association was more robust in studies using scales administered by a researcher, compared to self-report scales. DISCUSSION: The cognitive assessment is important not only as a parameter for determining QoL of patients, but also as a factor to be taken into account when analyzing the data obtained by self-report QoL scales.

OBJETIVO: Realizar a adaptação transcultural de instrumento para avaliação das alterações comportamentais tipicamente descritas em portadores de epilepsia do lobo temporal (ELT), o Inventário Neuro-Comportamental (NBI) para a população brasileira. MÉTODOS: Inicialmente, foi feita a tradução do instrumento original para o português. Esta versão foi revisada e retrotraduzida para o inglês. A seguir, a versão retrotraduzida foi comparada à versão original em inglês, sendo corrigidas as divergências no texto em português. Em um segundo momento, 15 pacientes do Ambulatório de Epilepsia do Hospital das Clínicas da UFMG portadores de ELT responderam ao inventário. À aplicação do questionário, eventuais dificuldades e os itens mal compreendidos foram analisados pelos autores. RESULTADOS: Na versão final para o português, os itens 11, 14, 17, 61 e 75 foram modificados. Sete pacientes (46,7%) eram do sexo feminino, com idade entre 26 e 65 anos. A maioria dos pacientes (93,3%) apresentou uma pontuação total elevada. Os domínios mais comumente alterados foram hiperreligiosidade, detalhismo e crença na predestinação pessoal (73,3% dos pacientes em cada um deles). CONCLUSÃO: A versão em português do NBI pode ser um instrumento útil para avaliar alterações comportamentais na ELT aplicada ao contexto clínico dos pacientes brasileiros.

To discuss paroxysmal events that mimic epileptic seizures with emphasis on their semiologic differences and therapeutic perspectives. We did a narrative review of the literature based on selected papers in Medline and Bireme after searching for the uniterms "non-epileptic seizures" and "psychogenic seizures". Nonepileptic seizures (NES) can be classified in physiological (syncope, migraine, transitory ischemic attack) and psychogenic (voluntary or involuntary). The gold-standard in the differentiation of epileptic and nonepileptic seizures is the video-electroencefalogram, but many semiologic features can contribute to this process. The treatment of NES is based mainly on psychotherapy and pharmacotherapy directed to comorbid psychiatric disorders. Despite the high prevalence and elevated morbidity of the NES, there are just few studies on this subject in the Brazilian literature. There are many diagnostic and therapeutic challenges related to NES. Hence, psychiatrists should be aware of the occurrence of NES, avoiding iatrogenic interventions such as the unnecessary administration of anti-epileptic drugs.

CONTEXTO: Uma síndrome amnésica clássica caracteriza-se por evidente prejuízo da memória anterógrada, variável e temporária amnésia retrógrada, sendo as formas não-declarativas da memória poupadas. Entretanto, publicações recentes relataram casos de prejuízo desproporcional da memória retrógrada em relação à anterógrada. OBJETIVOS: Relatar o caso de um paciente de 26 anos de idade com um quadro grave de amnésia retrógrada, aparentemente sem fatores desencadeantes. MÉTODOS: Entrevista psiquiátrica e avaliação neuropsicológica. RESULTADOS: A perda de memória do paciente se estendia por toda sua vida, mas ele era capaz de adquirir e reter novas informações. Ele também apresentava prejuízos na produção e na compreensão de palavras, assim como no reconhecimento e no uso de objetos. CONCLUSÃO: A formulação diagnóstica final do caso é difícil, apontando possivelmente o contínuo existente entre a amnésia retrógrada psicogênica e a orgânica. BACKGROUND: A classic amnestic syndrome is characterized by a significant impairment of the anterograde memory, a variable and transitory retrograde amnesia with preserved non-declarative memory. However, case reports of patients with disproportionate compromise of the retrograde memory have been described in the recent literature. OBJECTIVES: To report a 26-year-old patient with a severe global retrograde amnesia with no evident triggering factor. METHODS: Psychiatric interview and neuropsychological evaluation. RESULTS: His memory loss compromised all domains of his life, although he could acquire and retain new information. He also exhibited prominent deficits in production and comprehension of common words as well as in recognition and use of objects. DISCUSSION: The final diagnostic formulation of the present case is difficult possibly indicating a continuum between psychogenic and organic retrograde amnesia.

INTRODUÇÃO: A epilepsia é um problema de saúde pública. Afeta mais de cinqüenta milhões de pessoas em todo mundo e mais de vinte milhões deles continuam apresentando crises que não controlam satisfatoriamente com o uso de medicamentos. As epilepsias refratárias correspondem a cerca de 20% dos pacientes epilépticos e boa parte desses apresentam crises parciais complexas passíveis de tratamento cirúrgico. A indicação cirúrgica criteriosa tem se mostrado eficiente para o controle das crises. OBJETIVO: Apresentar dados epidemiológicos e cirúrgicos dos pacientes submetidos ao tratamento cirúrgico no NATE. METODOLOGIA: Estudo retrospectivo com análise de prontuários e classificação do controle de crises de 46 pacientes considerando a Escala de Engel. RESULTADOS: Predomina o sexo masculino, solteiros, sem história familiar para epilepsia. Pacientes procedentes do Estado de Minas Gerais e outros estados da união. Início das crises na infância para 58,8% dos pacientes sendo o tipo de crise mais freqüente a crise parcial complexa. O déficit de memória foi a queixa cognitiva mais comum. CONCLUSÃO: O controle de crise foi compatível com Engel Ia (sem crise) para 67% dos pacientes. O tratamento cirúrgico revelou-se eficiente para o controle das crises dos pacientes portadores de epilepsia refratária ao tratamento medicamentoso. INTRODUCTION: Epilepsy is a health public problem. Afflicts more than 50 million people worldwide, and more than 20 million of those affected do not have satisfactory seizures control with medicine. The refractory epilepsy represents 20% of all epileptic patients and most of them present partial seizures which can be treated by surgical treatment. The careful surgical recommendation can be efficient to seizure control. PURPOSE: The aim of this study was to present epidemiological and surgical data about patients submitted to surgical treatment in NATE - Advanced Center of Epilepsy Treatment. METHOD: We used a retrospective assessment method and control seizure classification from Engel Scale for 46 epileptic patients submitted to surgical treatment. RESULTS: Our results showed predominant male patients, single, without family history for epilepsy. The patients were from cities of Minas Gerais State and from another States in Brazil. The first seizure occurred in the childhood for 58,8% of patients and the more frequent seizure type was complex partial seizure. The predominant cognitive complaint was about memory. CONCLUSION: The surgical treatment for seizure control was good for 67% of patients that display Engel Ia classification (without seizures) and has a high likelihood for success in medically intractable temporal lobe epilepsy.

Prefrontal cortex (PFC) dysfunction can lead to impairment in planning and behavioral inhibition, as well as personality changes. As ascending monoaminergic brainstem systems modulate PFC functioning, it is possible that lesions in the brainstem lead to symptoms similar to prefrontal dysfunction. A 29-year-old man developed several cognitive and behavioral symptoms after neurosurgery for resection of a pilocytic astrocytoma in the pontine-mesencephalic area. A careful analysis of symptoms indicated PFC dysfunction that could be attributed to lesions in the ascending monoaminergic brainstem systems. Interestingly, the cognitive symptoms improved after treatment with methylphenidate, which is a drug that modules catecholaminergic neurotransmission, thereby supporting this hypothesis. This is a unique case of PFC dysfunction that may be related to post-operative lesion of the catecholaminergic nuclei in the brainstem.

We report a 67-year-old man with Parkinson's disease for 9 years who developed compulsive use of levodopa. This phenomenon is the main feature of the dopamine dysregulation syndrome. Other related symptoms presented by our patient were mood fluctuation and increased writing activity suggestive of punding.

OBJETIVO: O uso de modelos experimentais tem permitido importantes avanços no diagnóstico e na terapêutica de doenças somáticas, tais como diabetes e hipertensão. No caso da esquizofrenia, entretanto, as tentativas de modelos experimentais causaram, historicamente, pouco impacto e algum ceticismo. Estudos mais recentes, contudo, indicam que a Ciência Cognitiva aplicada ao uso de modelos pode nos ajudar na compreensão da fisiopatologia da esquizofrenia. O estudo objetivou realizar uma revisão crítica dos modelos experimentais propostos para a esquizofrenia. RESULTADOS E DISCUSSÃO: As dificuldades próprias dos modelos de esquizofrenia são a subjetividade dos sintomas, a dificuldade em reproduzi-los em animais e a complexidade clínica a ser totalizada. Fenótipo tão complexo só pode ser abordado pela separação de seus componentes (endofenótipos) e pela respectiva manipulação de seus correlatos experimentais, feita por intervenções específicas (e.g. farmacológicas, cirúrgicas, genéticas) na busca de um mecanismo comum para estes endofenótipos. A correlação entre resultados e sintomas deve apoiar-se em hipótese explanatória abrangente. Até o presente, a doença parece envolver desconexão neuronal difusa decorrente de anormalidades cerebrais sutis, de causa genética e/ou ambiental. CONCLUSÕES: A integração da informação dos modelos atualmente em uso pode contribuir de modo significativo para a compreensão da esquizofrenia. OBJECTIVE: Diagnostic and therapy of somatic diseases like diabetes and hypertension have improved notably with the use of experimental models. For schizophrenia the proposal of a model has made little impact and even scepticism. Nevertheless the most recent studies indicate that "Cognitive Sciences" applied to specific models may help us to find out mechanisms of the disease. This article reviews the models presently under investigation for schizophrenia. RESULTS AND DISCUSSION: The difficulty to model schizophrenia results from the subjectivity of its symptoms, the difficult to reproduce them in animals and the disease complexity. Research on such a complex phenotype can only proceed by separating its components (endophenotypes) from each other and by the respective manipulation of its experimental counterparts, made by specific interventions (e.g. pharmacological, surgical, genetic), in the search of a common mechanism leading to these endophenotypes. For integrating these findings with symptoms a global explanatory theory is required. So far, the disease seems to result from a diffuse neuronal disconnection as a consequence of minor brain abnormalities with a genetic and/or environmental cause. CONCLUSIONS: An integrative approach of the diversity of models presently used may improve our understanding of schizophrenia.

Background Bipolar disorder (BD) diagnosis is based on specific set of mood and behavioural symptoms although they also exhibit cognitive dysfunction. Immune/inflammatory mechanisms have been implicated in the pathophysiology of BD. Objective To investigate whether cognitive functioning is associated with clinical parameters and immune profile in patients with BD in remission. Methods Twenty patients with BD type I in remission (15/20 female; age [mean ± SD] 43.80 ± 11.72 years; years of education [mean ± SD] 12.40 ± 3.39) and 25 healthy controls (16/25 female; age [mean ± SD] 43.52 ± 11.72 years; years of education [mean ± SD] 11.16 ± 2.66) matched for age, gender, and years of education were enrolled in this study. Subjects were evaluated with the Mini-Plus; Young Mania Rating Scale; Hamilton Depression Rating Scale; and with Brief Assessment of Cognition in Affective Disorders a comprehensive test battery to evaluate visuomotor, immediate affective and non-affective memory, verbal fluency, delayed affective and non-affective memory, inhibition, and problem solving domains. We assessed IL2, IL4, IL6, IL10, IL17, INF, TNF and its soluble receptors in plasma by flow cytometry. Results Patients with BD exhibited poorer performance on all cognitive domains in comparison with controls. Patients with BD also had high levels of soluble TNF receptors, and Th1/Th2/Th17 cytokines (p Conclusion Our data suggest that inflammatory dysfunction might contribute to the cognitive impairment in BD.

The study investigates the effects of acute and chronic oral treatment with Hypericum perforatum L. (HP LI 160, 62.5-500 mg/kg) in rats submitted to different anxiety models: the elevated T-maze (for inhibitory avoidance and escape measurements), the light/dark transition, and the cat odor test. These models were selected for their presumed capacity of evidencing specific subtypes of anxiety disorders as recognized in clinical practice. The results showed that acute HP (125 mg/kg) impaired elevated T-maze inhibitory avoidance, an anxiolytic effect, without altering escape performance. Chronic HP (250 mg/kg) enhanced avoidance latencies only in animals that were preexposed to the open arms of the maze. Preexposure shortens escape latency, improving it as an escape index. Differently from the reference drug imipramine (IMP, 15 mg/kg), chronic HP did not impair escape from the open arms of the maze. On the other hand, similarly to IMP, the extract increased the number of transitions between the two compartments in the light/dark transition model. Treatment regimens with HP and IMP did not alter behavioral responses of rats to a cloth impregnated with cat odor. These observations suggest that HP LI 160 exerts anxiolytic-like effects in a specific subset of defensive behaviors, particularly those related to generalized anxiety.

O termo ecstasy é usado para descrever diversas substâncias que compartilham estruturas químicas e efeitos semelhantes, referindo-se mais comumente a 3,4-metilenodioximetanfetamina (3,4-MDMA). Os efeitos psíquicos da MDMA são, sobretudo, alucinógenos e estimulantes. A tendência atual considera o delírio de Cotard como sendo a crença delirante de estar morto ou de que seus órgãos estejam paralisados ou podres, independentemente do diagnóstico do paciente. Neste artigo, relatamos o caso clínico de um paciente que apresentou quadro psicótico com delírios hipocondríacos e alucinações olfativas com características de síndrome de Cotard associado ao uso crônico de ecstasy. Foi medicado com olanzapina e obteve remissão completa dos sintomas.

We report the case of a patient with temporal lobe epilepsy, nonresponsive to antiepileptic drugs, who became seizure-free, but developed recurrent excessive irritability and psychotic symptoms after successful mesial temporal lobectomy. This patient was refractory to various pharmacological treatments including antipsychotics, mood stabilizers, and benzodiazepines before being successfully treated with olanzapine.

Animal models of psychiatric disorders are a challenging but highly relevant issue. Most psychiatric disorders are very heterogeneous syndromes, resulting from multiple and varied causal factors and characterized by symptoms that can only be inferred with significant limitations in non-human models. As constructing a model that reproduces a whole psychiatric syndrome seems virtually impossible, researchers have tried to focus on endophenotypes, i.e., discrete traits that are more proximal to predisposing genes than the whole syndrome. These can be explored in a wide range of approaches, such as in pharmacological, lesion, and environmental models. Another challenge is to understand how genes interact with environmental factors over time to result in the syndromic phenotype. A better understanding of the subcellular mechanisms that enhance or allow brain resistance to environmental influences is required, as is a global thesis compatible with the diversity of diseases sharing similar behavioral and biological traits. With an experimental inventory of the possible causes of minor developmental failures, we may systematically explore their consequences in the adult animal and be able to decide if this will enlighten the understanding of one or another psychiatric disease.

Schizophrenia is a chronic psychiatric syndrome characterized by generalized cognitive deficits that are associated with functional impairment. The endocannabinoid system (ECS) modulates neurotransmission and neuronal plasticity and is important for cognitive functioning. Evidence points to the involvement of this neuromodulatory system in the pathophysiology of schizophrenia and that alteration of the ECS on peripheral lymphocytes could reflect central changes. The objective of this study was to compare levels of peripheral endocannabinoid receptor expression in patients with schizophrenia and healthy subjects and find evidence of association between peripheral expression of those receptors and cognitive performance. Patients with stabilized schizophrenia (N=53) and controls (N=22) underwent clinical and cognitive evaluation, and assessment of cannabinoid receptor expression on the surface of peripheral immune cells (lymphocytes, natural killer cells and monocytes) by flow cytometry. Patients with schizophrenia had lower levels of cannabinoid receptor expression on total T lymphocytes, but after controlling for possible confounders this difference did not remain significant. In patients, increased cannabinoid receptor expression on lymphocytes and monocytes was significantly correlated with worst cognitive performance. These data provide additional evidence of the involvement of the ECS in the pathophysiology of cognitive deficits in schizophrenia.

OBJECTIVE: Schizophrenia is a psychiatric disorder whose mechanisms have remained only partially elucidated. The current proposals regarding its biological basis, such as the dopaminergic hypothesis, do not fully explain the diversity of its symptoms, indicating that other processes may be involved. This paper aims to review evidence supporting the involvement of the endocannabinoid system (ECS), a neurotransmitter group that is the target of Cannabis sativa compounds, in this disorder. METHODS: A systematic review of original papers, published in English, indexed in PubMed up to April, 2012. RESULTS: Most studies employed genetics and histological, neuroimaging or neurochemical methods - either in vivo or post-mortem - to investigate whether components of the ECS are compromised in patients. Overall, the data show changes in cannabinoid receptors in certain brain regions as well as altered levels in endocannabinoid levels in cerebrospinal fluid and/or blood. CONCLUSIONS: Although a dysfunction of the ECS has been described, results are not entirely consistent across studies. Further data are warrant to better define a role of this system in schizophrenia. OBJETIVO: A esquizofrenia é um transtorno psiquiátrico cujos mecanismos permanecem apenas parcialmente elucidados. As atuais propostas relativas à base biológica, tais como a hipótese dopaminérgica, não explicam por completo a diversidade de seus sintomas, o que indica que outros processos podem estar envolvidos. Este artigo tem como objetivo revisar indícios que sustentem o envolvimento do sistema endocanabinoide (SECB), um grupo de neurotransmissoresalvo dos compostos da Cannabis sativa, nesse transtorno. MÉTODOS: Revisão sistemática dos artigos originais, publicados em inglês e indexados no PubMed até abril de 2012. RESULTADOS: A maioria dos estudos empregou métodos neuroquímicos ou de neuroimagem genéticos e histológicos - tanto in vivo quanto post-mortem - para investigar se os componentes do SECB estão comprometidos nos pacientes. De modo geral, os dados mostram mudanças nos receptores canabinoides em determinadas regiões cerebrais, bem como a alteração dos níveis de endocanabinoides no líquido cefalorraquidiano e/ou no sangue. CONCLUSÕES: Ainda que a disfunção do SECB tenha sido descrita, os resultados dos estudos não são totalmente consistentes. São necessários mais dados para definir melhor o papel desse sistema na esquizofrenia.

Interview-based scales can be used as coprimary measures to complement the assessment of cognitive impairment in schizophrenia. One major question that arises from the use of such tools is how specific they are in relation to other psychopathological domains. We analyse the specificity of the Positive and Negative Syndrome Scale (PANSS) negative subscale and the Schizophrenia Cognition Rating Scale (SCoRS).We performed a principal component analysis (PCA) of PANSS negative subscale, rated by the interviewer, and SCoRS ratings from three different sources (patient, informant, and interviewer) in 101 patients with schizophrenia. Additionally, we correlated mean SCoRS ratings to PANSS negative subscale items to determine whether any PANSS item is particularly related to cognition.The PCA showed that the two first components, which explained approximately 40% of the total variance of the scales, represent the SCoRS ratings and the PANSS negative subscale ratings, respectively. The mean interviewer SCoRS was significantly correlated with the PANSS negative Item 5 (difficulty in abstract thinking) and with the mean PANSS negative subscale. The latter correlation was no longer significant when "difficulty in abstract thinking" was eliminated from PANSS negative subscale.In general, SCoRS and PANSS negative subscale scores address different constructs; however, the PANSS negative item "difficulty in abstract thinking" seems to address a cognitive dimension.

This review article gives an overview of a number of central neuro-transmitters, which are essential for integrating many functions in the central nervous system (CNS), such as learning, memory, sleep cycle, body movement, hormone regulation and many others. Neurons use neuro-transmitters to communicate, and a great variety of molecules are known to fit the criteria to be classified as such. A process shared by all neuro-transmitters is their release by excocytosis, and we give an outline of the molecular events and protein complexes involved in this mechanism. Synthesis, transport, inactivation, and cellular signaling can be very diverse when different neuro-transmitters are compared, and these processes are described separately for each neuro-transmitter system. Here we focus on the most well known neuro-transmitters: acetyl-choline, catechol-amines (dopamine and nor-adrenalin), indole-amine (serotonin), glutamate, and gamma-amino-butyric acid (GABA). Glutamate is the major excitatory neuro-transmitter in the brain and its actions are counter-balanced by GABA, which is the major inhibitory substance in the CNS. A balance of neuronal transmission between these two neuro-transmitters is essential to normal brain function. Acetyl-choline, serotonin and catechol-amines have a more modulatory function in the brain, being involved in many neuronal circuits. Apart from summarizing the current knowledge about the synthesis, release and receptor signaling of these transmitters, some disease states due to alteration of their normal neuro-transmission are also described.

Diagnostic and therapy of somatic diseases like diabetes and hypertension have improved notably with the use of experimental models. For schizophrenia the proposal of a model has made little impact and even scepticism. Nevertheless the most recent studies indicate that "Cognitive Sciences" applied to specific models may help us to find out mechanisms of the disease. This article reviews the models presently under investigation for schizophrenia.The difficulty to model schizophrenia results from the subjectivity of its symptoms, the difficult to reproduce them in animals and the disease complexity. Research on such a complex phenotype can only proceed by separating its components (endophenotypes) from each other and by the respective manipulation of its experimental counterparts, made by specific interventions (e.g. pharmacological, surgical, genetic), in the search of a common mechanism leading to these endophenotypes. For integrating these findings with symptoms a global explanatory theory is required. So far, the disease seems to result from a diffuse neuronal disconnection as a consequence of minor brain abnormalities with a genetic and/or environmental cause.An integrative approach of the diversity of models presently used may improve our understanding of schizophrenia.

The sensitivity of latent inhibition (LI) to amphetamine has been tested in humans with a paradigm close to the conditioned emotional response suppression currently used in experimental animals. The conditioned stimulus (CS) was a tone, the unconditioned stimulus (US) a strong white noise, and the response a transient delay in a regular sequence of hand movements in the resolution of the Tower of Toronto puzzle. The aim of this study was to verify whether the previously reported, disruptive effect of CS preexposure on conditioning really represents LI, by examining its sensitivity to amphetamine. Three groups of healthy volunteers received placebo, 5 or 10 mg of dexamphetamine sulphate, respectively, in a double-blind experimental design. The preexposure, conditioning and test phases were carried out under either amphetamine or placebo. The non preexposed groups treated with amphetamine were not different from the non preexposed placebo group, indicating that amphetamine did not affect conditioning. Among the preexposed groups, those receiving 10 mg of amphetamine showed normal rates of conditioning, whereas those treated with either 5 mg of amphetamine or placebo showed LI. Similar results have been reported in experimental animals. This sensitivity to amphetamine suggests that the present paradigm may be used to study LI in humans.

A paradigm based on conditioned suppression of ongoing motor activity, sensitive to latent inhibition (LI), was developed and tested in healthy volunteers. Subjects were trained to move disks from one peg to another with a high degree of regularity in the Tower of Toronto puzzle, a well-known cognitive skill learning task. Once this was achieved, they were submitted to a Pavlovian conditioning procedure. The conditioned stimulus (CS) was a pure tone and the unconditioned stimulus (US) a loud white noise. The resulting response suppression was assessed by a transient increase in latency of the hand movements. In control subjects, there was non-contingent CS and US presentation. The results evidenced conditioning after a single CS-US pairing. Following five preexposures to the to-be-conditioned CS, however, conditioning was abolished, seemingly expressing LI. Because a weak unconditioned response to the tone was observed after its first two presentations, an additional experiment was performed with two preexposures to the to-be-conditioned CS. With such procedure, conditioning was obtained, supporting the existence of LI in the preceding experiment. These results indicate that the present paradigm may be useful for the study of LI in human subjects, having the advantage of being similar to the experimental conditions used in the majority of LI studies in experimental animals.

The effect of benzodiazepines on the nociceptive threshold was studied in rats using the tail-flick and the formalin tests. Systemic injection of midazolam (10 mg/kg, i.p.) induced a significant decrease of the tail-flick latency and produced a long-lasting nociceptive effect in the formalin test, thus characterising a hyperalgesic state. The hyperalgesia induced by midazolam in the tail-flick test was blocked by flumazenil, a specific antagonist for benzodiazepine sites associated with GABA(A) receptors. Picrotoxin, a Cl- channel blocker, inhibited midazolam-induced hyperalgesia in both tests. Midazolam caused hyperalgesia when administered intracerebroventricularly (i.c.v.; 25 microg) but not intrathecally (i.t.; 75 microg). I.c.v. but not i.t. (5 microg) injection of flumazenil suppressed the hyperalgesia induced by midazolam (10 mg/kg, i.p.). Combination of non-hyperalgesic doses of diazepam (10 mg/kg, i.p.) or ethanol (0.48 g/kg, oral) with midazolam (5 mg/kg, i.p.) also induced hyperalgesia. Our results demonstrate that midazolam and diazepam alone or in combination with ethanol can produce hyperalgesia by interacting with GABA(A) receptors at the supraspinal level in rats. The risk of hyperalgesia should be taken in account when these drugs are used in combination in humans.