Structural and Functional Deviations of the Hippocampus in Schizophrenia and Schizophrenia Animal Models.

Schizophrenia is a grave neuropsychiatric disease which frequently onsets between the end of adolescence and the beginning of adulthood. It is characterized by a variety of neuropsychiatric abnormalities which are categorized into positive, negative and cognitive symptoms. Most therapeutical strategies address the positive symptoms by antagonizing D2-dopamine-receptors (DR). However, negative and cognitive symptoms persist and highly impair the life quality of patients due to their disabling effects. Interestingly, hippocampal deviations are a hallmark of schizophrenia and can be observed in early as well as advanced phases of the disease progression. These alterations are commonly accompanied by a rise in neuronal activity. Therefore, hippocampal formation plays an important role in the manifestation of schizophrenia. Furthermore, studies with animal models revealed a link between environmental risk factors and morphological as well as electrophysiological abnormalities in the hippocampus. Here, we review recent findings on structural and functional hippocampal abnormalities in schizophrenic patients and in schizophrenia animal models, and we give an overview on current experimental approaches that especially target the hippocampus. A better understanding of hippocampal aberrations in schizophrenia might clarify their impact on the manifestation and on the outcome of this severe disease.

Bright, but allergic and neurotic? A critical investigation of the "overexcitable genius" hypothesis.

Introduction: Higher intelligence has been associated with improved health and longevity. However, recent findings have claimed that exceptional intelligence may come at a cost. Individuals at the upmost end of the intelligence distribution are reported to be disproportionately afflicted by a set of stress-related physical and mental health conditions: so-called overexcitabilities. Few accounts have investigated this issue and no studies are available for non-US samples yet. Here, we aimed to replicate and extend previous work by examining hitherto unaddressed overexcitabilities in a European high-IQ sample. Methods: We carried out a preregistered survey among members of MENSA, the world's largest high-IQ society. In total, 615 (307 male) members from Austria, Germany, Hungary, Switzerland, and the United Kingdom participated. Results and Discussion: Compared to the general population, our sample exhibited considerably elevated prevalences in autism spectrum disorders (risk ratio/RR = 2.25), chronic fatigue syndrome (RR = 5.69), depression (RR = 4.38), generalized anxiety (RR = 3.82), and irritable bowel syndrome (RR = 3.76). Contrary to previous accounts, neither asthma, allergies, nor autoimmune diseases were elevated. We show that this subsample of intellectually gifted persons faces specific health challenges compared to the general population. The reasons for this remain speculative, as we find little evidence for previously proposed immunological explanations. However, it is possible that the effects are caused by sample selectiveness (i.e., membership in a high-IQ society) rather than high IQ itself.

Emotional development of gifted students: comparative study about overexcitabilities / Desenvolvimento emocional de alunos superdotados: estudo comparativo acerca das sobre-excitabilidades / Desarrollo emocional de estudiantes superdotados: estudio comparativo sobre las sobreexcitabilidades

The aim of this study was to compare gifted, with academic and artistic talent, and non-gifted students regarding overexcitability, as well as to investigate the perceptions of teachers from a specialized educational program for the gifted about their students' emotional development. The study included 150 students and six teachers. As instruments, we used participants characterization questionnaires, an overexcitability scale and a semi-structured interview script. Data were analyzed using inferential statistics and content analysis. The results indicated significant differences between gifted and non-gifted students in the patterns of intellectual and imaginative over-excitability, as well as a tendency for teachers to emotionally characterize gifted students with an emphasis on psychological disorders and weaknesses. To invest in educational strategies that use information derived from overexcitability patterns as facilitating tools for the learning process of the gifted can contribute to increasing student engagement at school, keeping them motivated. (AU)

O objetivo deste estudo foi comparar estudantes superdotados, com talento acadêmico e artístico, e não superdotados em relação às sobre-excitabilidades, bem como investigar a percepção de professores de um atendimento educacional especializado a alunos com altas habilidades/superdotação acerca do desenvolvimento emocional de seus estudantes. Participaram do estudo 150 discentes, além de seis professores. Como instrumentos foram utilizados questionários de caracterização dos participantes, escala de sobre-excitabilidade e roteiro de entrevista semiestruturado. Os dados foram analisados mediante estatística inferencial e análise de conteúdo. Os resultados indicaram diferenças significativas entre estudantes superdotados e não superdotados nos padrões de sobre-excitabilidades intelectual e imaginativa, bem como uma tendência dos professores em caracterizar emocionalmente os alunos superdotados com ênfase em transtornos e fragilidades psicológicas. Investir em estratégias educacionais que utilizem informações decorrentes dos padrões de sobre-excitabilidade como instrumentos facilitadores do processo de aprendizagem dos superdotados pode contribuir para aumentar o envolvimento dos alunos na escola, mantendo-os motivados. (AU)

El objetivo de este estudio fue comparar estudiantes superdotados, con talento académico y artístico, y no-superdotados en relación con la sobreexcitabilidad, así como investigar la percepción de docentes de un servicio educativo especializado para superdotados sobre el desarrollo emocional de sus alumnos. El estudio incluyó a 150 estudiantes y seis profesores. Como instrumentos se utilizaron cuestionarios de caracterización de los participantes, una escala de sobreexcitabilidad y un guión de entrevista semiestructurada. Los datos se analizaron mediante estadística inferencial y análisis de contenido. Los resultados indicaron diferencias significativas entre los superdotados y no-superdotados en las sobreexcitabilidades intelectual e imaginativa, así como una tendencia de los profesores a caracterizar emocionalmente a los superdotados con énfasis en los trastornos psicológicos y las debilidades. Invertir en estrategias educativas que utilicen información derivada de la sobreexcitabilidad como herramientas facilitadoras del proceso de aprendizaje de los superdotados puede contribuir a aumentar la participación de los estudiantes en la escuela, manteniéndolos motivados. (AU)

Dotação intelectual: comparações entre avaliação por teste e nomeação por pais / Intellectual giftedness: comparisons between assessment testing and nomination by the parents / Dotación intelectual: comparaciones entre evaluación por prueba y nombramiento por padres

Este estudo teve como objetivo comparar dois tipos de medidas (Teste de Raciocínio e Nomeação por Pais) utilizadas na avaliação de dotação intelectual. Para tanto, aplicaram-se a Bateria de Provas de Raciocínio (BPR-5) e a versão para pais das Escalas de Sobre-Excitabilidade, mais especificamente a escala de Sobre-Excitabilidade Intelectual (SEI), em alunos do ensino fundamental (n=67) e em seus pais ou responsáveis (n=67), respectivamente. Ao comparar as duas medidas, observou-se que os estudantes que apresentaram melhor desempenho no escore geral da BPR-5 também tenderam a apresentar médias mais altas na SEI. Foram obtidas correlações positivas, significativas, que variaram de fracas a moderadas, entre a SEI, a capacidade cognitiva geral e alguns tipos de raciocínio (verbal, abstrato e numérico). A comparação e as associações positivas entre os dois instrumentos permitem sugerir que ambos investigam construtos correlatos. Entretanto, as medidas devem ser consideradas como complementares e não substitutivas. (AU)

This study aimed to compare two types of measures (reasoning test and parent's nomination) used in the assessment of intellectual giftedness. Accordingly, the Reasoning Test Battery (BPR-5) and the parents version of the Overexcitability Scales, more specifically the Intellectual Overexcitability scale (SEI) were applied with elementary school students (n=67) and their parents or guardians (n=67), respectively. When comparing the two measures, it was observed that students who performed better in the BPR-5 also tended to receive higher means in the SEI. Significant positive correlations, which ranged from weak to moderate, were obtained between the SEI, the general reasoning ability, and some types of reasoning (verbal, abstract, and numeric). The comparison and positive associations between the two instruments indicate that both investigate related constructs. However, the measures should be considered as complementary rather than substitutive. (AU)

Este estudio tuvo como objetivo comparar dos tipos de medidas (prueba de raciocinio y nombramiento por padres) utilizadas en la evaluación de dotación intelectual. Razón por la cual, se aplicaron la Batería de Pruebas de Razonamiento (BPR-5) y la versión para padres de las Escalas de Sobreexcitabilidad, más específicamente se aplicó la Escala de Sobreexcitabilidad Intelectual (SEI) en alumnos de la enseñanza básica (n=67) y en sus padres o responsables (n=67). Al comparar las dos medidas, se observó que los estudiantes que presentan mejor desempeño en la BPR-5, también tienden en presentar medias más altas en la SEI. Se obtuvo correlaciones positivas, significativas y débiles entre la SEI y la capacidad general de razonamiento. La SEI también se correlacionó positiva y significativamente con algunos tipos de razonamiento (Verbal, Abstracto y Numérico). La comparación y las asociaciones positivas entre los dos instrumentos permiten sugerir que ambos investigan constructos relacionados. Con todo, las medidas deben ser consideradas como complementarias y no substitutivas. (AU)

Invariância fatorial e normatização das escalas de sobre-excitabilidade / Factorial invariance and norming of the overexcitabilities scales / Invariancia factorial y estandarización de las escalas de sobre-excitabilidad

Este estudo teve como objetivos estabelecer normas preliminares e verificar a estrutura e invariância fatorial das Escalas de Sobre-Excitabilidade (ESE) de acordo com o sexo. Trata-se de uma medida destinada à avaliação de sobre-excitabilidade ­ tendência para reagir intensa e sensivelmente a estímulos nas áreas sensorial, psicomotora, imaginativa, emocional e intelectual. Participaram 1500 estudantes do ensino fundamental de cinco estados brasileiros. Análises fatoriais confirmatórias demonstraram bons índices de ajustes para os modelos testados, revelando a existência de 11 escalas. Apesar de haver diferenças quanto ao sexo nos escores médios de algumas escalas, análises fatoriais confirmatórias multigrupos indicaram a invariância fatorial da medida nos grupos masculino e feminino. A normatização preliminar foi estabelecida a partir do cálculo do percentil acumulado para os escores totais e por sexo. Esses resultados evidenciam propriedades psicométricas adequadas e constituem um avanço para a normatização das ESE. (AU)

This study aimed to establish preliminary norms and verify the structure and factorial invariance of the Overexcitabilities Scales (OS) according to sex. It is a measure for the assessment of overexcitability - tendency to react intensely and sensitively to stimuli in Sensual, Psychomotor, Imaginative, Emotional, and Intellectual areas. Participants included 1500 elementary school students from five Brazilian states. Confirmatory factor analysis demonstrated good adjustment indices for the tested models, revealing the existence of 11 scales. Although there were differences regarding sex in the mean scores of some scales, confirmatory multigroup factor analysis indicated the factorial invariance of the measure in male and female groups. The preliminary norms were established by calculating the cumulative percentile for the total scores and sex. These results show adequate psychometric properties and represent progress for OES norming. (AU)

Este estudio tuvo como objetivo establecer normas preliminares y verificar estructura e invariancia factorial de las Escalas de Sobre-excitabilidad (ESE) en función del sexo. Es una medida destinada a evaluar la sobre-excitabilidad - tendencia a reaccionar intensa y sensiblemente a los estímulos en las áreas Sensorial, Psicomotora, Imaginativa, Emocional e Intelectual. Participaron 1500 estudiantes de Enseñanza Primaria de cinco estados brasileños. Análisis factoriales confirmatorios demostraron buen índice de ajuste en los modelos testados, revelando la existencia de 11 escalas. Aunque existen diferencias en función de sexo en los resultados medios de algunas escalas, análisis factorial confirmatorio multigrupos indicaron invariancia factorial de la medida en los grupos masculino y femenino. La estandarización preliminar fue establecida a partir del cálculo de porcentaje acumulado para los resultados totales y por sexo. Esos resultados muestran propiedades psicométricas adecuadas y constituyen un gran avance para la estandarización de las escalas de sobre-excitabilidad. (AU)

Escalas de sobre-excitabilidade: construção e evidências de validade baseadas no conteúdo e na estrutura interna / Overexcitability scales: construction, validity evidence based on content and on internal structure

ResumoEste estudo teve como objetivo desenvolver uma medida de sobre-excitabilidade (SE) - tendência para reagir intensa e sensivelmente a estímulos - e obter evidências de validade baseadas no conteúdo e na estrutura interna dessa medida. Para tanto, foram necessárias duas etapas de pesquisa. Na primeira, que detalha a construção das Escalas de Sobre-Excitabilidade (ESE), foram realizadas análises por juízes (N = 9) e aplicação piloto (N = 18). Estudantes do Ensino Fundamental (N =263) participaram da segunda etapa para verificação das propriedades psicométricas do instrumento. Obteve-se um conjunto de cinco escalas que avaliam cinco padrões de SE (Psicomotor, Sensorial, Imaginativo, Intelectual e Emocional). Observou-se alta concordância entre os juízes e a aplicação piloto foi bem sucedida. Os valores de consistência interna das escalas foram considerados adequados. A maioria dos itens apresentou correlação item-total aceitável. Estruturas multidimensionais foram observadas nos padrões Psicomotor, Sensorial e Emocional nas análises fatoriais confirmatórias. Bons índices de ajustes para os modelos testados foram obtidos. Esses resultados constituem evidências de validade baseadas no conteúdo e na estrutura interna para as ESE. Portanto, a medida possui propriedades psicométricas iniciais adequadas.

AbstractThis study aimed to develop a measure of overexcitability (OE) - tendency to react intensely and sensitively to stimuli - and obtain validity evidences based on the content and internal structure of this measure. For this, two phases of research were necessary. In the first phase, which details the construction of Overexcitability Scales (OS), analysis by judges (N=9) and pilot application (N=18) were performed. Elementary school students (N=263) participated in the second phase to verify the psychometric properties of the instrument. A set of five scales that assess five OE patterns (Psychomotor, Sensual, Imaginative, Intellectual and Emotional) was obtained. There was high correlation among the judges and the pilot application was successful. The internal consistency values of the scales were considered adequate. Most items showed acceptable item-total correlation. Multidimensional structures were observed in Psychomotor, Sensual, and Emotional patterns in the confirmatory factor analyzes. Good indexes of adjustment to the models tested were obtained. These results constitute validity evidence based on content and internal structure to the OS. Therefore, the measure has appropriate initial psychometric properties.

Psychometric Evaluation of the Overexcitability Questionnaire-Two Applying Bayesian Structural Equation Modeling (BSEM) and Multiple-Group BSEM-Based Alignment with Approximate Measurement Invariance.

The Overexcitability Questionnaire-Two (OEQ-II) measures the degree and nature of overexcitability, which assists in determining the developmental potential of an individual according to Dabrowski's Theory of Positive Disintegration. Previous validation studies using frequentist confirmatory factor analysis, which postulates exact parameter constraints, led to model rejection and a long series of model modifications. Bayesian structural equation modeling (BSEM) allows the application of zero-mean, small-variance priors for cross-loadings, residual covariances, and differences in measurement parameters across groups, better reflecting substantive theory and leading to better model fit and less overestimation of factor correlations. Our BSEM analysis with a sample of 516 students in higher education yields positive results regarding the factorial validity of the OEQ-II. Likewise, applying BSEM-based alignment with approximate measurement invariance, the absence of non-invariant factor loadings and intercepts across gender is supportive of the psychometric quality of the OEQ-II. Compared to males, females scored significantly higher on emotional and sensual overexcitability, and significantly lower on psychomotor overexcitability.

Preclinical evaluation of marketed sodium channel blockers in a rat model of myotonia discloses promising antimyotonic drugs.

Although the sodium channel blocker mexiletine is considered the first-line drug in myotonia, some patients experiment adverse effects, while others do not gain any benefit. Other antimyotonic drugs are thus needed to offer mexiletine alternatives. In the present study, we used a previously-validated rat model of myotonia congenita to compare six marketed sodium channel blockers to mexiletine. Myotonia was induced in the rat by injection of anthracen-9-carboxylic acid, a muscle chloride channel blocker. The drugs were given orally and myotonia was evaluated by measuring the time of righting reflex. The drugs were also tested on sodium currents recorded in a cell line transfected with the human skeletal muscle sodium channel hNav1.4 using patch-clamp technique. In vivo, carbamazepine and propafenone showed antimyotonic activity at doses similar to mexiletine (ED50 close to 5mg/kg); flecainide and orphenadrine showed greater potency (ED50 near 1mg/kg); lubeluzole and riluzole were the more potent (ED50 near 0.1mg/kg). The antimyotonic activity of drugs in vivo was linearly correlated with their potency in blocking hNav1.4 channels in vitro. Deviation was observed for propafenone and carbamazepine, likely due to pharmacokinetics and multiple targets. The comparison of the antimyotonic dose calculated in rats with the current clinical dose in humans strongly suggests that all the tested drugs may be used safely for the treatment of human myotonia. Considering the limits of mexiletine tolerability and the occurrence of non-responders, this study proposes an arsenal of alternative drugs, which may prove useful to increase the quality of life of individuals suffering from non-dystrophic myotonia. Further clinical trials are warranted to confirm these results.