Cognitive control associated with irritability induction: an autobiographical recall fMRI study

OBJECTIVE: Despite the relevance of irritability emotions to the treatment, prognosis and classification of psychiatric disorders, the neurobiological basis of this emotional state has been rarely investigated to date. We assessed the brain circuitry underlying personal script-driven irritability in healthy subjects (n = 11) using functional magnetic resonance imaging. METHOD: Blood oxygen level-dependent signal changes were recorded during auditory presentation of personal scripts of irritability in contrast to scripts of happiness or neutral emotional content. Self-rated emotional measurements and skin conductance recordings were also obtained. Images were acquired using a 1,5T magnetic resonance scanner. Brain activation maps were constructed from individual images, and between-condition differences in the mean power of experimental response were identified by using cluster-wise nonparametric tests. RESULTS: Compared to neutral scripts, increased blood oxygen level-dependent signal during irritability scripts was detected in the left subgenual anterior cingulate cortex, and in the left medial, anterolateral and posterolateral dorsal prefrontal cortex (cluster-wise p-value < 0.05). While the involvement of the subgenual cingulate and dorsal anterolateral prefrontal cortices was unique to the irritability state, increased blood oxygen level-dependent signal in dorsomedial and dorsal posterolateral prefrontal regions were also present during happiness induction. CONCLUSION: Irritability induction is associated with functional changes in a limited set of brain regions previously implicated in the mediation of emotional states. Changes in prefrontal and cingulate areas may be related to effortful cognitive control aspects that gain salience during the emergence of irritability.

Cardiac response and anxiety levels in psychopathic murderers

OBJECTIVE: To compare the emotional response and level of anxiety of psychopathic murderers, non-psychopathic murderers, and nonpsychopathic non-criminals. METHOD: 110 male individuals aged over 18 years were divided into three groups: psychopathic murderers (n = 38); non-psychopathic murderers (n = 37) serving sentences for murder convictions in Maximum Security Prisons in the State of Sao Paulo; and non-criminal, non-psychopathic individuals (n = 35) according to the Psychopathy Checklist-Revised. The emotional response of subjects was assessed by heart rate variation and anxiety level (State-Trait Anxiety Inventory) after viewing standardized pictures depicting pleasant, unpleasant and neutral content from the International Affective Picture System. RESULTS: Psychopathic murderers presented lower anxiety levels and smaller heart rate variations when exposed to pleasant and unpleasant stimuli than nonpsychopathic murderers or non-psychopathic non-criminals. The results also demonstrated that the higher the score for factor 1 on the Psychopathy Checklist-Revised, the lower the heart rate variation and anxiety level. CONCLUSION: The results suggest that psychopathic murderers do not present variation in emotional response to different visual stimuli. Although the non-psychopathic murderers had committed the same type of crime as the psychopathic murderers, the former tended to respond with a higher level of anxiety and heart rate variation.

Wives of pathological gamblers: personality traits, depressive symptoms and social adjustment

Objective: Wives of pathological gamblers tend to endure long marriages despite financial and emotional burden. Difficulties in social adjustment, personality psychopathology, and comorbidity with psychiatric disorders are pointed as reasons for remaining on such overwhelming relationships. The goal was to examine the social adjustment, personality and negative emotionality of wives of pathological gamblers. Method: The sample consisted of 25 wives of pathological gamblers, mean age 40.6, SD = 9.1 from a Gambling Outpatient Unit and at GAM-ANON, and 25 wives of non-gamblers, mean age 40.8, SD = 9.1, who answered advertisements placed at the Universidade de São Paulo hospital and medical school complex. They were selected in order to approximately match demographic characteristics of the wives of pathological gamblers. Subjects were assessed by the Social Adjustment Scale, Temperament and Character Inventory, Beck Depression Inventory and State-Trait Anxiety Inventory. Results: Three variables remained in the final Multiple Logistic Regression model, wives of pathological gamblers presented greater dissatisfaction with their marital bond, and higher scores on Reward Dependence and Persistence temperament factors. Both, Wives of pathological gamblers and wives of non-gamblers presented well-structured character factors excluding personality disorders. Conclusion: This personality profile may explain wives of pathological gamblers emotional resilience and their marriage longevity. Co-dependence and other labels previously used to describe them may work as a double edged sword, legitimating wives of pathological gamblers problems, while stigmatizing them as inapt and needy.

Applying a new version of the Brazilian-Portuguese UPSIT smell test in Brazil

Standardized olfactory tests are now available to quantitatively assess disorders of olfaction. A Brazilian-Portuguese version of the University of Pennsylvania Smell Identification Test (UPSIT) is currently being developed specifically for the Brazilian population. The most recent Brazilian-Portuguese version of the UPSIT (UPSIT-Br2) was administered to 88 Brazilian subjects who had no history of neurological or otorhinolaryngological disease. UPSIT-Br2 scores decreased with age, were lower in men than in women, and were lower in subjects with lower income. The degree to which the poorer performance of subjects with lower socio-economic status reflects lack of familiarity with test items is not known. Although this version of the UPSIT provides a sensitive and useful test of smell function for the Brazilian population, a revision of some test items is needed to achieve comparable norms to those found using the North American UPSIT in the United States.

Reaction time assessment in children with ADHD

Attention deficit, impulsivity and hyperactivity are the cardinal features of attention deficit hyperactivity disorder (ADHD) but executive function (EF) disorders, as problems with inhibitory control, working memory and reaction time, besides others EFs, may underlie many of the disturbs associated with the disorder. OBJECTIVE: To examine the reaction time in a computerized test in children with ADHD and normal controls. METHOD: Twenty-three boys (aged 9 to 12) with ADHD diagnosis according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, 2000 (DSM-IV) criteria clinical, without comorbidities, Intelligence Quotient (IQ) >89, never treated with stimulant and fifteen normal controls, age matched were investigated during performance on a voluntary attention psychophysical test. RESULTS: Children with ADHD showed reaction time higher than normal controls. CONCLUSION: A slower reaction time occurred in our patients with ADHD. This findings may be related to problems with the attentional system, that could not maintain an adequate capacity of perceptual input processes and/or in motor output processes, to respond consistently during continuous or repetitive activity.

Hormônio do crescimento e exercício físico: considerações atuais

Embora o hormônio do crescimento (GH) seja um dos hormônios mais estudados, vários de seus aspectos fisiológicos ainda não estão integralmente esclarecidos, incluindo sua relação com o exercício físico. Estudos mais recentes têm aumentado o conhecimento a respeito dos mecanismos de ação do GH, podendo ser divididos em: 1) ações diretas, mediadas pela rede de sinalizações intracelulares, desencadeadas pela ligação do GH ao seu receptor na membrana plasmática; e 2) ações indiretas, mediadas principalmente pela regulação da síntese dos fatores de crescimento semelhantes à insulina (IGF). Tem sido demonstrado que o exercício físico é um potente estimulador da liberação do GH. A magnitude deste aumento sofre influência de diversos fatores, em especial, da intensidade e do volume do exercício, além do estado de treinamento. Atletas, normalmente, apresentam menor liberação de GH induzida pelo exercício que indivíduos sedentários ou pouco treinados. Evidências experimentais demonstram que o GH: 1) favorece a mobilização de ácidos graxos livres do tecido adiposo para geração de energia; 2) aumenta a capacidade de oxidação de gordura e 3) aumenta o gasto energético.

Enzyme kinetics, structural analysis and molecular modeling studies on a series of Schistosoma mansoni PNP inhibitors

The enzyme purine nucleoside phosphorylase from Schistosoma mansoni (SmPNP) is an attractive molecular target for the development of novel drugs against schistosomiasis, a neglected tropical disease that affects about 200 million people worldwide. In the present work, enzyme kinetic studies were carried out in order to determine the potency and mechanism of inhibition of a series of SmPNP inhibitors. In addition to the biochemical investigations, crystallographic and molecular modeling studies revealed important molecular features for binding affinity towards the target enzyme, leading to the development of structure-activity relationships (SAR).

Structural and chemical basis for anticancer activity of a series of 'beta'-tubulin ligands: molecular modeling and 3D QSAR studies

An important approach to cancer therapy is the design of small molecule modulators that interfere with microtubule dynamics through their specific binding to the ²-subunit of tubulin. In the present work, comparative molecular field analysis (CoMFA) studies were conducted on a series of discodermolide analogs with antimitotic properties. Significant correlation coefficients were obtained (CoMFA(i), q² =0.68, r²=0.94; CoMFA(ii), q² = 0.63, r²= 0.91), indicating the good internal and external consistency of the models generated using two independent structural alignment strategies. The models were externally validated employing a test set, and the predicted values were in good agreement with the experimental results. The final QSAR models and the 3D contour maps provided important insights into the chemical and structural basis involved in the molecular recognition process of this family of discodermolide analogs, and should be useful for the design of new specific ²-tubulin modulators with potent anticancer activity.

Drug consumption among medical students in São Paulo, Brazil: influences of gender and academic year

OBJECTIVE: To analyze alcohol, tobacco and other drug use among medical students. METHOD: Over a five-year period (1996-2001), we evaluated 457 students at the Universidade de São Paulo School of Medicine, located in São Paulo, Brazil. The students participated by filling out an anonymous questionnaire on drug use (lifetime, previous 12 months and previous 30 days). The influence that gender and academic year have on drug use was also analyzed. RESULTS: During the study period, there was an increase in the use of illicit drugs, especially inhalants and amphetamines, among the medical students evaluated. Drug use (except that of marijuana and inhalants) was comparable between the genders, and academic year was an important influencing factor. DISCUSSION: Increased inhalant use was observed among the medical students, especially among males and students in the early undergraduate years. This is suggestive of a specific behavioral pattern among medical students. Our findings corroborate those of previous studies. CONCLUSION: Inhalant use is on the rise among medical students at the Universidade de São Paulo School of Medicine. Because of the negative health effects of illicit drug use, further studies are needed in order to deepen the understanding of this phenomenon and to facilitate the development of preventive measures.

Seasonality of suicide in the city of Sao Paulo, Brazil, 1979-2003

OBJECTIVE: To evaluate suicide seasonality in the city of São Paulo within an urban area and tropical zone. METHOD: Suicides were evaluated using the chi-square test and analysis of variance (ANOVA) by comparing monthly, quarterly and half-yearly variations, differentiating by gender. Analyses of time series were carried out using the autocorrelation function and periodogram, while the significance level for seasonality was confirmed with the Fisher's test. RESULTS: The suicides of the period between 1979 and 2003 numbered 11,434 cases. Differences were observed in suicides occurring in Spring and Autumn for the total sample (ANOVA: p-value = 0.01), and in the male sample (ANOVA: p-value = 0.02). For the analysis of time series, seasonality was significant only for the period of 7 months in the male sample (p-value = 0.04). DISCUSSION: In this study, no significant seasonal differences were observed in the occurrences of suicides, with the exception of the male sample. The differences observed did not correspond with the pattern described in studies carried out in temperate zones. Some of the climatic particularities of the tropical zone might explain the atypical pattern of seasonality of suicides found in large populations within an urban area and tropical zone.

O uso de videogames, jogos de computador e internet por uma amostra de universitários da Universidade de São Paulo

OBJETIVO: Avaliar uso de jogos eletrônicos (videogames, jogos de computador e internet) em uma amostra de universitários. MÉTODO: Um questionário a respeito de comportamentos relacionados ao uso de jogos eletrônicos, contendo a escala Problem Videogame Playing (PVP), foi aplicado em 100 alunos da Universidade de São Paulo (USP). RESULTADOS: A maioria (83%) relatou ter jogado no último ano, dentre a qual 81,9% eram homens, 51,8% jogavam de 1 a 2 horas por sessão; 74,4% afirmaram que jogar não interfere em seus relacionamentos sociais e 60,5%, que o uso de jogos violentos não influencia sua agressividade. Os estudantes dividiram-se entre jogadores ocasionais e frequentes, diferenciando-se por duração de cada sessão, jogo preferido, motivação para jogar, e influência do jogo na vida social. Cerca de 5% relataram só parar de jogar quando interrompidos, normalmente jogar mais de 4 horas por sessão e se relacionar mais com amigos virtuais, sugerindo maior envolvimento com a atividade. Na escala PVP, 15,8% da amostra preencheu mais da metade dos itens, indicando consequências adversas associadas ao uso dos jogos eletrônicos. CONCLUSÃO: Observou-se que o uso de jogos eletrônicos é comum entre os estudantes da USP e que uma parcela apresenta problemas relacionados ao excesso de jogo.

Caracterização e distribuição de cronotipos no sul do Brasil: diferenças de gênero e estação de nascimento

OBJETIVO: Investigar a tipologia circadiana e as diferenças de gênero em universitários do sul do Brasil. MÉTODOS: Voluntários (736) de 17 a 49 anos preencheram a versão brasileira do Questionário de Cronotipo (QC), tradução do Morningness-eveningness Questionnaire (MEQ) de Horne e Östberg. Medidas de tendência central e dispersão e curva de distribuição dos escores do QC (Kolmogorov-Smirnov) foram calculadas de acordo com gênero (teste t de Student), idade, estação de nascimento e desconforto com o horário de verão (qui-quadrado). RESULTADOS: Foram incluídos 648 indivíduos (36% homens, 64% mulheres), com perdas de 12% por questionários incorretos. A distribuição dos escores do QC evidenciou uma curva normal (amplitude = 18-77; média = 46,6; desvio-padrão = 10,8). Nesta amostra, 32% foram vespertinos, 54% intermediários e 14% matutinos. As médias do QC foram significativamente diferentes (p = 0,003): homens (44,9 ± 10,8) comparados com mulheres (47,5 ± 10,7) e 70% dos que nasceram na primavera e no verão foram vespertinos (p = 0,015), sem associação gênero-estação do ano. CONCLUSÃO: Homens e nascidos na primavera-verão evidenciaram preferência pela vespertinidade, não havendo diferença de gênero com relação à estação de nascimento. Nossos resultados estão de acordo com estudos realizados no hemisfério norte que mostraram, também, uma associação entre a estação de nascimento e o cronotipo.

A reabilitação neuropsicológica sob a ótica da psicologia comportamental

CONTEXTO: A reabilitação neuropsicológica é um dos componentes do tratamento de clientes* com lesões cerebrais e/ou distúrbios neurológicos e neuropsiquiátricos. Os programas de reabilitação podem se beneficiar do emprego de procedimentos** comportamentais, principalmente porque a ciência da análise do comportamento dispõe de ferramentas valiosas para a modificação do comportamento e o auxílio nos processos de aprendizagem. OBJETIVOS: Este artigo objetiva discursar sobre a interação entre as áreas de reabilitação neuropsicológica e análise do comportamento. MÉTODOS: Inicia-se esta empreitada apresentando o que é a reabilitação neuropsicológica, passando pela clarificação do emprego de procedimentos comportamentais tanto na avaliação como na reabilitação neuropsicológicas e quais os cuidados necessários na preparação de um programa. RESULTADOS: Objetiva-se, assim, despertar o interesse pelo desenvolvimento de novos estudos neste vasto campo e chamar a atenção dos neuropsicólogos para a importância da aquisição de conhecimentos básicos em análise do comportamento. CONCLUSÃO: Isso parece ser conseqüência não da escassez de estudos sobre o emprego de procedimentos comportamentais em programas de reabilitação neuropsicológica, mas sim da falta de percepção, por parte dos profissionais de reabilitação, de que muitos procedimentos por eles empregados são comportamentais. Ou pode ainda refletir um desconhecimento sobre a existência da vertente da neuropsicologia comportamental, ou ainda ser apenas reflexo dos preconceitos de que a análise do comportamento é alvo.

Neuromodulation approaches for the treatment of major depression: challenges and recommendations from a working group meeting

The use of neuromodulation as a treatment for major depressive disorder (MDD) has recently attracted renewed interest due to development of other non-pharmacological therapies besides electroconvulsive therapy (ECT) such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). METHOD: We convened a working group of researchers to discuss the updates and key challenges of neuromodulation use for the treatment of MDD. RESULTS: The state-of-art of neuromodulation techniques was reviewed and discussed in four sections: [1] epidemiology and pathophysiology of MDD; [2] a comprehensive overview of the neuromodulation techniques; [3] using neuromodulation techniques in MDD associated with non-psychiatric conditions; [4] the main challenges of neuromodulation research and alternatives to overcome them. DISCUSSION: ECT is the first-line treatment for severe depression. TMS and tDCS are strategies with a relative benign profile of side effects; however, while TMS effects are comparable to antidepressant drugs for treating MDD; further research is needed to establish the role of tDCS. DBS and VNS are invasive strategies with a possible role in treatment-resistant depression. In summary, MDD is a chronic and incapacitating condition with a high prevalence; therefore clinicians should consider all the treatment options including invasive and non-invasive neuromodulation approaches.

Working memory impairment in multiple sclerosis relapsing-remitting patients with episodic memory deficits

Episodic memory is impaired in multiple sclerosis (MS) patients, possibly because of deficits in working memory (WM) functioning. If so, WM alterations should necessarily be found in patients with episodic memory deficits, but this has not yet been demonstrated. In this study we aimed at determining whether episodic memory deficits in relapsing-remitting MS are found in conjunction with impaired WM. We evaluated 32 MS patients and 32 matched healthy controls. Nineteen of the 32 patients had episodic memory impairment, and as a group only these individuals showed deficits in WM capacity, which may lead to difficulty in encoding, and/or retrieving information from episodic memory.