Perda significativa de peso em pacientes com esquizofrenia na dieta hipocalórica de longo prazo: estudo piloto / Significant weight loss in patients with schizophrenia in long-term hypocaloric diet: a pilot study

Objetivo: A esquizofrenia está associada ao aumento da obesidade e morbidade por doença cardiovascular. O objetivo do presente estudo foi avaliar alterações no peso e índice de massa corporal (IMC) de pacientes com esquizofrenia após tratamento nutricional de longo prazo. Método: Estudo piloto retrospectivo envolvendo 42 indivíduos com esquizofrenia em tratamento nutricional entre 2004 e 2010. Os prontuários médicos foram revisados após aprovação institucional e coleta de dados para peso, índice de massa corporal (IMC), idade, gênero e dieta. O peso e o IMC foram avaliados no início do tratamento nutricional, após seis meses, após 12 meses e no momento da coleta de dados. Resultados: Houve perda significativa de peso e diminuição significativa do IMC quando comparados a cada grupo com o valor basal (p<0,001). Conclusões: Demonstramos que as intervenções nutricionais podem promover uma significativa perda de peso na esquizofrenia. Estes resultados suportam a importância da intervenção nutricional na esquizofrenia e trazem evidências de que a perda de peso permanece ao longo do tempo.(AU)

Objective: Schizophrenia is associated with increased obesity and morbidity from cardiovascular disease. The aim of the present study was to evaluate changes in weight and body mass index (BMI) of patients with schizophrenia following a long-term nutritional treatment. Methods: Retrospective pilot study involving 42 individuals with schizophrenia on nutritional treatment from 2004 to 2010. Medical charts were reviewed after institutional approval and data collection was conducted for weight, body mass index (BMI), age, gender and diet prescription. Weight and BMI were evaluated at baseline of nutrition treatment, after six months, after 12 months and at the time of data collection. Results: There was a significant weight loss and significant decreased in BMI when compared each group to baseline (p<0.001). Conclusions: We demonstrate that nutritional interventions can promote a significant weight loss in schizophrenia. These results support the importance of nutritional intervention in schizophrenia and bring evidences that weight loss remains along the time.(AU)

Schizophrenia and reelin: a model based on prenatal stress to study epigenetics, brain development and behavior

Schizophrenia is a severe psychiatric disorder that results in a significant disability for the patient. The disorder is characterized by impairment of the adaptive orchestration of actions, a cognitive function that is mainly dependent on the prefrontal cortex. This behavioral deficit, together with cellular and neurophysiological alterations in the prefrontal cortex, as well as reduced density of GABAergic cells and aberrant oscillatory activity, all indicate structural and functional deficits of the prefrontal cortex in schizophrenia. Among the several risk factors for the development of schizophrenia, stress during the prenatal period has been identified as crucial. Thus, it is proposed that prenatal stress induces neurodevelopmental alterations in the prefrontal cortex that are expressed as cognitive impairment observed in schizophrenia. However, the precise mechanisms that link prenatal stress with the impairment of prefrontal cortex function is largely unknown. Reelin is an extracellular matrix protein involved in the development of cortical neural connectivity at embryonic stages, and in synaptic plasticity at postnatal stages. Interestingly, down-regulation of reelin expression has been associated with epigenetic changes in the reelin gene of the prefrontal cortex of schizophrenic patients. We recently showed that, similar to schizophrenic patients, prenatal stress induces down-expression of reelin associated with the methylation of its promoter in the rodent prefrontal cortex. These alterations were paralleled with altered prefrontal cortex functional connectivity and impairment in prefrontal cortex-dependent behavioral tasks. Therefore, considering molecular, cellular, physiological and behavioral evidence, we propose a unifying framework that links prenatal stress and prefrontal malfunction through epigenetic alterations of the reelin gene.

Comparative analysis of non-adherence to medication treatment for systemic arterial hypertension in urban and rural populations / Análise comparativa da não adesão ao tratamento medicamentoso da hipertensão arterial sistêmica em população urbana e rural / Análisis comparativa de la no adhesión al tratamiento medicamentoso de la hipertensión arterial sistémica en población urbana y rural

OBJECTIVE: to evaluate the indexes and the main factors associated with non-adherence to medication treatment for systemic arterial hypertension between urban and rural areas. METHOD: analytical study based on an epidemiological survey with a sample of 247 hypertensive residents of rural and urban areas, with application of a socio-demographic and economic questionnaire, and treatment adherence assessment. The Pearson's Chi-square test was used and the odds ratio (OD) was calculated to analyze the factors related to non-adherence. RESULTS: the prevalence of non-adherence was 61.9% and it was higher in urban areas (63.4%). Factors significantly associated with non-adherence were: male gender (OR=1.95; 95% CI 1.08-3.50), age 20-59 years old (OR=2.51; 95% CI 1.44-4.39), low economic status (OR=1.95; 95% CI 1.09-3.47), alcohol consumption (OR=5.92, 95% CI 1.73-20.21), short time of hypertension diagnosis (OR=3.07; 95% CI 1.35-6.96) and not attending the health service for routine consultations (OR=2.45; 1.35-4.42). CONCLUSION: the socio-demographic/economic characteristics, lifestyle habits and how to relate to health services were the factors that presented association with non-adherence regardless of the place of residence. .

OBJETIVO: avaliar os índices e os principais fatores associados a não adesão ao tratamento medicamentoso da hipertensão arterial sistêmica, entre área urbana e rural. MÉTODO: estudo analítico baseado em inquérito epidemiológico, realizado com amostra de 247 hipertensos moradores das áreas rural e urbana, com aplicação de questionário sociodemográfico, econômico e avaliação da adesão. Foi utilizado o teste quiquadrado de Pearson e calculado o Odds Ratio (OD) para análise dos fatores relacionados a não adesão. RESULTADOS: a prevalência da não adesão foi de 61,9%, sendo maior na área urbana (63,4%). Os fatores que apresentaram associação estatisticamente significativa com a não adesão foram: gênero masculino (OR=1,95; IC95% 1,08-3,50), faixa etária entre 20 e 59 anos (OR=2,51; IC95% 1,44-4,39), baixa classe econômica (OR=1,95; IC95% 1,09-3,47), etilismo (OR=5,92; IC 95% 1,73-20,21), tempo curto de diagnóstico de hipertensão (OR=3,07; IC95% 1,35-6,96) e não procura pelo serviço de saúde para consultas de rotina (OR=2,45; 1,35-4,42). CONCLUSÃO: as características sociodemográficas, econômicas, hábitos de vida e o modo de relacionar-se com os serviços de saúde foram os fatores que apresentaram associação com a não adesão, independentemente do local de residência. .

OBJETIVO: evaluar los índices y los principales factores asociados a la no adhesión al tratamiento medicamentoso de la hipertensión arterial sistémica entre área urbana y rural. MÉTODO: estudio analítico basado en investigación epidemiológica desarrollada con una muestra de 247 hipertensos moradores del área rural y urbana, con aplicación de un cuestionario sociodemográfico, económico y evaluación de la adhesión. Fue utilizado la prueba chi-cuadrado de Pearson y calculado el odds ratio (OD) para análisis de los factores relacionados a la no adhesión. RESULTADOS: la prevalencia de la no adhesión correspondió a 61,9%, siendo mayor en el área urbana (63,4%). Los factores que mostraron asociación estadísticamente significativa con la no adhesión fueron: género masculino (OR=1,95; IC95% 1,08-3,50), rango de edad entre 20 a 59 años (OR=2,51; IC95% 1,44-4,39), clase económica baja (OR=1,95; IC95% 1,09-3,47), etilismo (OR=5,92; IC 95% 1,73-20,21), tiempo corto de diagnóstico de hipertensión (OR=3,07; IC95% 1,35-6,96) y no procurar el servicio de salud para consultas de rutina (OR=2,45; 1,35-4,42). CONCLUSIÓN: las características sociodemográficas/económicas, hábitos de vida y el modo de relacionar con los servicios de salud fueron los factores que mostraron asociación con la no adhesión independientemente del local de residencia. .

Study of Serum Selenium Levels in Schizophrenic Patients.

Deficiency and excess amount of trace elements play an important role in several well recognized diseases, studies are going on to establish their role in schizophrenia. Selenium and other trace elements are indispensable components for certain enzymes responsible for various metabolic processes in different tissues including the brain as they play important functional roles in peripheral and central nervous systems. Objectives: In this study, we examined the levels of selenium in serum of patients of schizophrenia and compare them with normal healthy controls. Selenium was also measured in acute and chronic stage of schizophrenia categorized on the basis of PANSS score and correlated by Spearman’s Correlation Coefficient (ρ) in total cases, acute cases and chronic cases. Method: The study population comprised 150 patients and 150 age matched controls. We measured levels of Selenium by AAS (Atomic Absorption Spectrophotometer). Results: We found that selenium levels were significantly lower in patients with schizophrenia than in the control group. The levels of micronutrients studied were also correlated with disease severity and duration but found non-significant relation. Conclusion: Evaluation of selenium levels in patients with schizophrenia could prove useful. There may be role of Selenium in the pathogenesis and course of Schizophrenia and new therapeutic approaches warrants further study.

6-Hydroxydopamine lesions in the medial prefrontal cortex of rats exposed to a peak-interval procedure

Impaired temporal control is symptomatic of several neurological disorders; recently, it has been implicated in schizophrenia. An animal model of schizophrenia using 6-hydroxydopamine (6-OHDA) infused to the medial pre-frontal cortex (mPFC) was employed to examine its effects on temporal control. Twelve rats were trained on a peak-interval procedure (PIP) until stable patterns of behavior were obtained. Rats infused with 6-OHDA responded less during peak trials and their peak functions were flatter than sham rats. These results are consistent with similar studies with transgenic mice with increased striatal dopamine D2 receptor activity. Lesions in the mPFC decreased motivation to respond in a PIP. These effects may be considered analogous to negative symptoms of schizophrenia...

Sinaptogénesis y esquizofrenia: rol de la proteína DISC 1 / Synaptogenesis and Schizophrenia: The role of DISC 1 protein

El presente trabajo aporta información respecto del posible rol en la esquizofrenia del gen DISC 1 y la proteína que este gen codifica. Se realiza un recorrido desde el hallazgo de la translocación cromosómica que llevó a su descubrimiento, hasta la perspectiva actual, que lo conceptualiza como un modulador funcional complejo. La mencionada translocación fue originariamente identificada en una familia escocesa, y se observó que cosegregaba con esquizofrenia y otros trastornos mentales. Actualmente, se considera a DISC 1 como una proteína central dentro de una red de interacciones con otras proteínas - lo que en varios trabajos se denomina interactoma -, tales como NDEL 1, LIS 1 y PDE 4B, entre otras.

This paper provides information regarding the possible role in schizophrenia of the DISC 1 gene and the protein it encodes. It is a tour from the discovery of the chromosomal translocation that led to its discovery, up to the current perspective, which is conceptualized as a complex functional modulator. The above translocation was originally identified in a Scottish family, and it was noted that it cosegregated with schizophrenia and other mental discorders. Currently, DISC 1 is considered as a central protein within its network of protein interactions (named as interactome in several papers), such as NDEL 1, LIS 1 and PDE 4B, among others.

Esquizofrenia en niños y adolescentes / Schizophrenia in children and adolescents

La población infantil y adolescente es considerada, junto con los ancianos y embarazadas, vulnerable por representar un sistema fisiológico que dista del adulto promedio para el cual están basadas la mayoría de prácticas terapéuticas. La esquizofrenia tiene una especial importancia en este grupo ya que es considerada una enfermedad del neurodesarrollo. Para poder instaurar un tratamiento adecuado resulta capital conocer los procesos y circuitos neurobilógicos que constituyen la base de la patología. Las hipótesis mejor estudiadas son la dopaminérgica, de la cual deriva el arsenal farmacológico actual, y la hipoglutamatérgica. Esta última invita al desarrollo de nuevas moléculas con potencial antipsicótico pero que no posean blancos terapéuticos dopaminérgicos. Hasta hoy, no existe un fármaco comercializado que actúe sobre las vías glutamatérgicas para tratar la esquizofrenia pero sí existen varios ejemplos en ensayos clínicos de fases I y II. También es necesario establecer las pautas de dosificación para los grupos vulnerables las cuales derivan, en su mayoría, de las establecidas para adultos.

The population of children and adolescents is considered, along with the elderly and pregnant women, vulnerable, for representing a physiological system that is far from the average adult, for whom most therapeutic practices are based on. Schizophrenia has special relevance within this group, since it is considered a neurodevelopmental disorder. In order to establish an adquate treatment, it is key to know the processes and neurobiological circuits which form the basis of this disease. The best studied hypotheses are the dopaminergic hypothesis, from which the current pharmacological studies derive, and the hypoglutamatergic hypothesis. The latter proposes the development of new molecules with antipsychotic potential, which do not have dopaminergic therapeutic targets. Up to now, there is no marketed drug which acts on glutamatergic pathways to treat schizophrenia, although several examples can be found in phase I and II clinical trials. It is also necessary to establish dosing guidelines for vulnerable groups, most of which result from the ones established for adults.

Study of Lipid Derangement in Pyschiatric Disorder.

Background: Several studies have investigated the relationships of lipid levels with psychiatric patients and their results revealed an association between lipid derangement and psychiatric disorders. The aim of our study is to evaluate the lipid profile alteration in psychiatric disorder and compare with normal control. Materials and Methods: This study was conducted at People’s College of Medical Sciences and Research Centre, Bhopal. Sixty newly diagnosed psychiatric patients were included in this study and compare with 40 normal subjects. In both the groups we have measured lipid profile which includes serum total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), very low density lipoprotein cholesterol (VLDL), and cardiovascular risk factors (R-1and R2). Results: The levels of serum TC, TG, LDL-C and VLDL-C and risk factors in psychiatric patients was significantly increased as compared to control group (p<0.05). While serum HDL-C level was significantly decreased in test group (p > 0.05). Conclusion: In our study it is clearly evident that psychiatric disorders are associated with significantly higher levels of lipids (constituents of lipid profile) and risk factors for coronary heart disease.

Esquizofrenia después de los 40 y su relación con los estrógenos: una revisión / [Schizophrenia after forty and its relation with estrogens].

There has been a lot of interest in the many aspects of women’s mental health especially after Kraepelin’s description of gender differences in 1896 and the implication of gonad hormones in explaining these differences. Studies on the effects of hormonal changes in mental health have mainly been focused on the various phases of the menstrual cycle, pregnancy and postpartum period; however, there is little research regarding menopause. During this period women are at risk of developing a new schizophrenic illness the so-called ’second peak’. Research has shown that estrogen acts as a protective factor due to its anti-dopaminergic properties, thus providing an explanation for the risk increase of a new psychotic disorder during menopause. This review article highlights the importance of a clear understanding of this phase of life in patients suffering from or who present a risk of developing schizophrenia.

The "selfish brain" hypothesis for metabolic abnormalities in bipolar disorder and schizophrenia / A hipótese do "cérebro egoísta" para alterações metabólicas no transtorno bipolar e na esquizofrenia

Metabolic abnormalities are frequent in patients with schizophrenia and bipolar disorder (BD), leading to a high prevalence of diabetes and metabolic syndrome in this population. Moreover, mortality rates among patients are higher than in the general population, especially due to cardiovascular diseases. Several neurobiological systems involved in energy metabolism have been shown to be altered in both illnesses; however, the cause of metabolic abnormalities and how they relate to schizophrenia and BD pathophysiology are still largely unknown. The "selfish brain" theory is a recent paradigm postulating that, in order to maintain its own energy supply stable, the brain modulates energy metabolism in the periphery by regulation of both allocation and intake of nutrients. We hypothesize that the metabolic alterations observed in these disorders are a result of an inefficient regulation of the brain energy supply and its compensatory mechanisms. The selfish brain theory can also expand our understanding of stress adaptation and neuroprogression in schizophrenia and BD, and, overall, can have important clinical implications for both illnesses (AU)

Alterações metabólicas são frequentes em pacientes com esquizofrenia e transtorno bipolar (TB), levando a uma alta prevalência de diabetes e síndrome metabólica nessa população. Além disso, as taxas de mortalidade entre pacientes são mais altas do que na população geral, especialmente em decorrência de doenças cardiovasculares. Vários sistemas neurobiológicos envolvidos no metabolismo energético têm demonstrado alterações nas duas doenças; no entanto, a causa das alterações metabólicas e a forma como elas se relacionam com a fisiopatologia da esquizofrenia e do TB ainda são arenas em grande parte desconhecidas. A teoria do "cérebro egoísta" é um paradigma recente que postula que, para manter estável seu próprio fornecimento de energia, o cérebro modula o metabolismo da energia na periferia regulando tanto a alocação quanto a ingestão de nutrientes. Apresentamos neste artigo a hipótese de que as alterações metabólicas observadas nesses transtornos são resultado de uma regulação ineficiente do fornecimento de energia do cérebro e seus mecanismos compensatórios. A teoria do cérebro egoísta também pode expandir nosso entendimento sobre a adaptação ao estresse e a neuroprogressão na esquizofrenia e no TB, e, acima de tudo, pode ter implicações clínicas importantes para as duas doenças (AU)

Alfabetización sobre esquizofrenia para estudiantes de medicina / Literacy among medical students on schizophrenia

Introducción: La alfabetización en salud mental (ASM) por parte de estudiantes y profesionales de la salud implica su capacidad para reconocer la enfermedad mental y su adecuado manejo, lo que constituye un elemento esencial para reducir el estigma y la brecha de tratamiento de los pacientes con esquizofrenia. Objetivo: Determinar la asociación entre el reconocimiento, causas atribuibles y tratamiento sugerido de la esquizofrenia, con el género y la percepción de agresividad (PA) en un grupo de estudiantes de medicina. Método: Noventa y ocho estudiantes de una universidad pública de la Ciudad de México completaron el Cuestionario de Concepto Público de Agresividad (CPA) para valorar la ASM y la PA. Resultados: El 94.9% de los estudiantes reconocieron la presencia de una enfermedad mental. Menos de la mitad (44.9%) consideraron las intervenciones psiquiátricas como las más adecuadas para el control de los síntomas. El reconocimiento de la enfermedad mental se asoció con el nivel de restricción del tratamiento sugerido por los hombres. Las etiologías psicológica y biopsicosocial de los síntomas fueron las más frecuentemente referidas. El 82.7% de los estudiantes consideraron que la persona descrita era agresiva. Conclusiones: La atribución biopsicosocial de los síntomas y la PA podrían estar relacionados con la sugerencia de tratamientos coercitivos. Las campañas de ASM para estudiantes de medicina deben abocarse a incrementar el conocimiento de opciones terapéuticas y de la prevalencia real y métodos de prevención de la agresividad de los pacientes con esquizofrenia.

Animal models of prenatal immune challenge and their contribution to the study of schizophrenia: a systematic review

Prenatal immune challenge (PIC) in pregnant rodents produces offspring with abnormalities in behavior, histology, and gene expression that are reminiscent of schizophrenia and autism. Based on this, the goal of this article was to review the main contributions of PIC models, especially the one using the viral-mimetic particle polyriboinosinic-polyribocytidylic acid (poly-I:C), to the understanding of the etiology, biological basis and treatment of schizophrenia. This systematic review consisted of a search of available web databases (PubMed, SciELO, LILACS, PsycINFO, and ISI Web of Knowledge) for original studies published in the last 10 years (May 2001 to October 2011) concerning animal models of PIC, focusing on those using poly-I:C. The results showed that the PIC model with poly-I:C is able to mimic the prodrome and both the positive and negative/cognitive dimensions of schizophrenia, depending on the specific gestation time window of the immune challenge. The model resembles the neurobiology and etiology of schizophrenia and has good predictive value. In conclusion, this model is a robust tool for the identification of novel molecular targets during prenatal life, adolescence and adulthood that might contribute to the development of preventive and/or treatment strategies (targeting specific symptoms, i.e., positive or negative/cognitive) for this devastating mental disorder, also presenting biosafety as compared to viral infection models. One limitation of this model is the incapacity to model the full spectrum of immune responses normally induced by viral exposure.

Farmacología del epigenoma: investigaciones sobre usos de utilidad clínica de drogas estabilizantes del ánimo/anticonvulsivantes / Pharmacology of the epigenome: investigations on the use of clinical utility, of mood stabilizers/anticonvulsants

La epigenética es un promisorio campo de la investigación que probablemente contribuya a la comprensión de un amplio rango de enfermedades como la ansiedad, la depresión, la esquizofrenia, la enfermedad de Alzheimer, la enfermedad de Huntington o el síndrome de Rett. Esta área del conocimiento se refiere a las modificaciones en la expresión genética que resultan en cambios heredables y que son independientes de los cambios de la secuencia genética. Esto incluye la metilación del ácido desoxirribonucleico (ADN), las modificaciones de las histonas y más recientemente a la interferencia del ácido ribonucleico (ARN), especialmente a través de la no traducción a proteínas por microARN (miARN) u otros ARN pequeños de interferencia (SIRNA´s). La farmacología de la epigénetica está avanzando en el desarrollo de drogas o probando las utilizadas para otras indicaciones, para modificar las alteraciones del epigenoma que resultan en enfermedades o vulnerabilidades a diversas patologías.Los inhibidores de la deacetilasa de las histonas son un ejemplo de lo anteriormente expuesto. Demostraron tener eficacia como anticancerosos a través de un amplio rango de enfermedades malignas, especialmente las hematológicas. El valproato, un inhibidor de la deacetilasa de las histonas, es una droga que ha sido utilizada por décadas para tratar la epilepsia, los trastornos del estado de ánimo y la migraña y actualmente se lo investiga para otras indicaciones.El objetivo de este capítulo es mostrar los avances realizados en el conocimiento de los mecanismos de acción de drogas utilizadas como estabilizantes del estado de ánimo/anticonvulsivantes, como también sus probables usos por fuera de su indicación específica.

Epigenetics is a promising field of research, which probably contributes to understanding a wide spectrum of disorders such as anxiety, depression, schizophrenia, Alzheimer's Disease, Huntington's Disease or Rett's Syndrome. This area of knowledge refers to modifications in the gene expression, which result in inheritable changes and which are independent of the changes in the gene sequencing. This includes the methylation of deoxyribonucleic acid (DNA), the changes of histones, and, more recently, the role of ribonucleic acid (RNA), particularly, by means of non-protein-coding RNA (miRNA) or other small interfering RNA's (SIRNA's). The pharmacology of epigenetics is progressing in terms of the development of drugs, or the testing of the already used ones form other indications, in order to modify the alterations in the epigenome that result in diseases or vulnerabilities to different pathologies. Histone decetylase inhibitors are an example of the above. They prove to be effective against cancer through a wide spectrum of malignant diseases, especially hematologic diseases. Valprotate, a histone deacetylase inhibitor, is a drug which has been used for decades to treat epilepsy, mood disorders and migraines, and is currently being researched for other indications as well. The purpose of this chapter is to show the advances achieved with respect to the knowledge of the mechanisms of action of drugs used as mood stabilizers/anticonvulsants, as well as their possible uses beyond their possible uses beyond their specific indication.

pilot study evaluating the stigma and public perception about the causes of depression and schizophrenia

To evaluate public perceptions towards the causes of depression and schizophrenia and identifications of factors resulting stigma towards mental ill. A cross-sectional study was conducted among the inhabitants of Pulau-Pinang, Malaysia in March, 2009. A 24-item questionnaire was used to obtain respondent views. A non-probability [i.e convenient sampling method] was used to approach the potential respondents. Data analysis was conducted using SPSS version 13 [registerd], non-parametric statistics [Chi-square] was applied to determine the association. Alpha value less than 0.05 were considered significant. One hundred respondents showed their willingness to participate in the study; overall response of the study was 40.0%. Majority 69% of the respondents were Malays, followed by Chinese and Indians. Public recognition toward depression was higher than schizophrenia. Lack of social support [X[2]= 4.832, P= 0.049], chemical imbalance in Brian [X[2]=6.132, P= 0.013*] and believes in supernatural factors [X[2]= 6.700, P= 0.050] were the commonly shared reasons for the mental disorders. Evaluation in terms of stigma revealed that majority 61 [55.0%]. Individuals with mental disorders were not friendly [X[2]= 1.008, P= 0.050]. Furthermore, one third of the population believe that they are moody, dangerous and unpredictable, it is better to avoid them. Overall findings revealed that Malaysians believe in supernatural reasons for the prevalence of mental disorders. Similarly the level of stigma towards mentally ill was higher among the respondents