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Progressive supranuclear palsy (PSP) is a severe, debilitating, and often fatal disease resembling other neurodegenerative disorders, namely Alzheimer's (AD) and Parkinson's (PD) diseases, which have been successfully treated with cannabinoids. We herein report the case of a 71-year-old woman diagnosed with PSP, displaying severe impairment of motor and language functions which progressively improved after treatment with medical cannabis. Before treatment, the patient was unable to move her limbs, was fed soft food, and was unable to speak or move her eyes. The patient has regained horizontal eye movement, is able to walk with assistance, has returned to physiotherapy, started to eat solid food, and has had a remarkable improvement in her speech. The possible mechanisms of this improvement are discussed.
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ABSTRACT Anxiety and obsessive-compulsive related disorders are highly prevalent and disabling disorders for which there are still treatment gaps to be explored. Fear is a core symptom of these disorders and its learning is highly dependent on the activity of the neurotrophin brain-derived neurotrophic factor (BDNF). Should BDNF-mediated fear learning be considered a target for the development of novel treatments for anxiety and obsessive-compulsive related disorders? We review the evidence that suggests that BDNF expression is necessary for the acquisition of conditioned fear, as well as for the recall of its extinction. We describe the findings related to fear learning and genetic/epigenetic manipulation of Bdnf expression in animals and BDNF allelic variants in humans. Later, we discuss how manipulation of BDNF levels represents a promising potential treatment target that may increase the benefits of therapies that extinguish previously conditioned fear.
RESUMO Os transtornos da ansiedade e o transtorno obsessivo-compulsivo (TOC) e transtornos relacionados são altamente prevalentes e incapacitantes. Apesar disso, ainda existem lacunas a serem exploradas em relação ao tratamento desses transtornos. O medo é um sintoma central desses transtornos e sua aprendizagem é altamente dependente da atividade do fator neurotrófico derivado do cérebro (BDNF). Porém, será que a aprendizagem de medo mediada pelo BDNF deve ser considerada um alvo para o desenvolvimento de novos tratamentos para transtornos da ansiedade, TOC e transtornos relacionados? Revisamos as evidências que sugerem que a expressão de BDNF é necessária para a aquisição do medo condicionado, bem como para a evocação de sua extinção. Descrevemos os resultados relacionados a aprendizagem de medo, manipulação genética e epigenética da expressão de Bdnf em animais e variantes alélicas de BDNF em seres humanos. Posteriormente, discutimos como a manipulação dos níveis de BDNF representa um alvo em potencial para o tratamento, o que pode aumentar os benefícios das terapias que extinguem o medo previamente condicionado.
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A Brazilian Health Technology Assessment Bulletin (BRATS) article regarding scientific evidence of the efficacy and safety of methylphenidate for treating attention deficit hyperactivity disorder (ADHD) has caused much controversy about its methods. Considering the relevance of BRATS for public health in Brazil, we critically reviewed this article by remaking the BRATS search and discussing its methods and results. Two questions were answered: did BRATS include all references available in the literature? Do the conclusions reflect the reviewed articles? The results indicate that BRATS did not include all the references from the literature on this subject and also that the proposed conclusions are different from the results of the articles chosen by the BRATS authors themselves. The articles selected by the BRATS authors showed that using methylphenidate is safe and effective. However, the BRATS final conclusion does not reflect the aforementioned and should not be used to support decisions on the use of methylphenidate.
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Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Estimulantes del Sistema Nervioso Central/uso terapéutico , Metilfenidato/uso terapéutico , Brasil , Niño , Humanos , Guías de Práctica Clínica como AsuntoRESUMEN
OBJECTIVE: Obsessive-compulsive disorder (OCD) is a common and debilitating psychiatric illness. Although a genetic component contributes to its etiology, no single gene or mechanism has been identified to the OCD susceptibility. The catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAO-A) genes have been investigated in previous OCD studies, but the results are still unclear. More recently, Taylor (2013) in a comprehensive meta-analysis of genetic association studies has identified COMT and MAO-A polymorphisms involved with OCD. In an effort to clarify the role of these two genes in OCD vulnerability, a family-based association investigation was performed as an alternative strategy to the classical case-control design. METHODS: Transmission disequilibrium analyses were performed after genotyping 13 single-nucleotide polymorphisms (eight in COMT and five in MAO-A) in 783 OCD trios (probands and their parents). Four different OCD phenotypes (from narrow to broad OCD definitions) and a SNP x SNP epistasis were also analyzed. RESULTS: OCD, broad and narrow phenotypes,were not associated with any of the investigated COMT and MAO-A polymorphisms. In addition, the analyses of gene-gene interaction did not show significant epistatic influences on phenotype between COMT and MAO-A. CONCLUSIONS: The findings do not support an association between DSM-IV OCD and the variants of COMT or MAO-A. However, results from this study cannot exclude the contribution of these genes in the manifestation of OCD. The evaluation of broader spectrum phenotypes could help to understand the role of these and other genes in the pathophysiology of OCD and its spectrum disorders.
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Catecol O-Metiltransferasa/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Monoaminooxidasa/genética , Trastorno Obsesivo Compulsivo/genética , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Alelos , Niño , Epistasis Genética , Familia , Femenino , Frecuencia de los Genes , Genotipo , Haplotipos , Humanos , Desequilibrio de Ligamiento , Masculino , Trastorno Obsesivo Compulsivo/epidemiología , Fenotipo , Adulto JovenRESUMEN
A Brazilian Health Technology Assessment Bulletin (BRATS) article regarding scientific evidence of the efficacy and safety of methylphenidate for treating attention deficit hyperactivity disorder (ADHD) has caused much controversy about its methods. Considering the relevance of BRATS for public health in Brazil, we critically reviewed this article by remaking the BRATS search and discussing its methods and results. Two questions were answered: did BRATS include all references available in the literature? Do the conclusions reflect the reviewed articles? The results indicate that BRATS did not include all the references from the literature on this subject and also that the proposed conclusions are different from the results of the articles chosen by the BRATS authors themselves. The articles selected by the BRATS authors showed that using methylphenidate is safe and effective. However, the BRATS final conclusion does not reflect the aforementioned and should not be used to support decisions on the use of methylphenidate.
O Boletim Brasileiro de Avaliação de Tecnologias em Saúde (BRATS), em matéria sobre as evidências científicas da eficácia e segurança do metilfenidato para o transtorno de déficit de atenção e hiperatividade (TDAH), gerou controvérsias sobre sua metodologia. Considerando a relevância do BRATS para a saúde pública no Brasil, realizou-se análise crítica dessa matéria ao refazer a busca do BRATS e discutir sua metodologia e achados. Foram respondidas duas perguntas:o BRATS incluiu todas as referências disponíveis na literatura? As conclusões refletiram os textos revisados? Identificou-se que o BRATS não incluiu todas as referências da literatura sobre o tema e que as conclusões propostas estão diferentes dos resultados dos artigos escolhidos pelos próprios autores do BRATS. Os artigos selecionados pelos autores do BRATS apontam para a eficácia e segurança do uso do metilfenidato. Entretanto, a conclusão final dos autores não reflete isso e não deveria ser usada como referência para orientar decisões sobre o uso do metilfenidato.
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Humanos , Niño , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Estimulantes del Sistema Nervioso Central/uso terapéutico , Metilfenidato/uso terapéutico , Brasil , Guías de Práctica Clínica como AsuntoRESUMEN
Copy number variations (CNVs) have been previously associated with several different neurodevelopmental psychiatric disorders, such as autism, schizophrenia, and attention deficit hyperactivity disorder (ADHD). The present study consisted of a pilot genome-wide screen for CNVs in a cohort of 16 patients with early-onset obsessive-compulsive disorder (OCD) and 12 mentally healthy individuals, using array-based comparative genomic hybridization (aCGH) on 44K arrays. A small rare paternal inherited microdeletion (â¼64 kb) was identified in chromosome 15q13.3 of one male patient with very early onset OCD. The father did not have OCD. The deletion encompassed part of the FMN1 gene, which is involved with the glutamatergic system. This finding supports the hypothesis of a complex network of several genes expressed in the brain contributing for the genetic risk of OCD, and also supports the glutamatergic involvement in OCD, which has been previously reported in the literature.
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Deleción Cromosómica , Cromosomas Humanos Par 15 , Trastorno Obsesivo Compulsivo/genética , Adolescente , Edad de Inicio , Estudios de Casos y Controles , Niño , Preescolar , Hibridación Genómica Comparativa , Variaciones en el Número de Copia de ADN , Proteínas Fetales/genética , Forminas , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Proteínas de Microfilamentos/genética , Proteínas Nucleares/genéticaRESUMEN
INTRODUÇÃO: O caráter familial do transtorno obsessivo-compulsivo (TOC) já é bem estabelecido. Ele segue o modelo complexo de transmissão genética que envolve a influência de diversos genes de pequeno efeito em interação com o ambiente. MÉTODOS: Foi realizada uma revisão sistemática de estudos de associação genética com o TOC por meio de busca de artigos publicados até 2012 nas bases de dados: PubMed, Embase e SciELO, usando os termos MeSH, seus associados ou sinônimos para "obsessive-compulsive disorder", "gene" e "genetic association studies". RESULTADOS: Foram selecionados 105 artigos cujos principais resultados foram agrupados em grupos de genes relacionados a serotonina, dopamina, glutamato, GABA, substância branca, hormônios, sistema imune e outros genes (MAO-A, BNDF, COMT). CONCLUSÃO: Há grande variabilidade nos achados de estudos de associação entre os diversos genes candidatos estudados e o TOC. Genes relacionados às vias glutamatérgicas são candidatos promissores, porém não há associação conclusiva entre nenhum dos genes candidatos estudados e o TOC. Estudos de associação com grande tamanho amostral, avaliação de subgrupos mais homogêneos do fenótipo e metanálises ainda são necessários.
BACKGROUND: Obsessive-compulsive disorder (OCD) segregates in families. It follows a complex model of genetic transmission, which involves the influence of several small effect genes interacting with the environment. METHODS: A systematic review of genetic association studies in OCD was performed. Articles published until 2012 were searched in the databases PubMed, Embase and SciELO using the terms of MeSH and its associates or synonyms for "obsessive-compulsive disorder", "gene" and "genetic association studies". RESULTS: We selected 105 papers and described their main results grouped as genes related to: serotonin, dopamine, glutamate, GABA, white matter, immune system, hormones and other genes. CONCLUSION: There is high variability between findings of association studies among the several candidate genes studied in OCD. Glutamate-related genes are promising candidates for OCD, but there is no conclusive association between any of the candidate genes studied and OCD. Association studies with large sample size, evaluation of more homogeneous subgroups of phenotype and meta-analyses are still needed.
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Genes , Trastorno Obsesivo Compulsivo , Dopamina , Serotonina , Ácido GlutámicoRESUMEN
OBJECTIVE: To evaluate the clinical features of obsessive-compulsive disorder (OCD) patients with comorbid tic disorders (TD) in a large, multicenter, clinical sample. METHOD: A cross-sectional study was conducted that included 813 consecutive OCD outpatients from the Brazilian OCD Research Consortium and used several instruments of assessment, including the Yale-Brown Obsessive-Compulsive Scale, the Dimensional Yale-Brown Obsessive-Compulsive Scale, the Yale Global Tic Severity Scale (YGTSS), the USP Sensory Phenomena Scale, and the Structured Clinical Interview for DSM-IV Axis I Disorders. RESULTS: The sample mean current age was 34.9 years old (SE 0.54), and the mean age at obsessive-compulsive symptoms (OCS) onset was 12.8 years old (SE 0.27). Sensory phenomena were reported by 585 individuals (72% of the sample). The general lifetime prevalence of TD was 29.0% (n = 236), with 8.9% (n = 72) presenting Tourette syndrome, 17.3% (n = 141) chronic motor tic disorder, and 2.8% (n = 23) chronic vocal tic disorder. The mean tic severity score, according to the YGTSS, was 27.2 (SE 1.4) in the OCD + TD group. Compared to OCD patients without comorbid TD, those with TD (OCD + TD group, n = 236) were more likely to be males (49.2% vs. 38.5%, p < .005) and to present sensory phenomena and comorbidity with anxiety disorders in general: separation anxiety disorder, social phobia, specific phobia, generalized anxiety disorder, post-traumatic stress disorder, attention-deficit hyperactivity disorder, impulse control disorders in general, and skin picking. Also, the "aggressive," "sexual/religious," and "hoarding" symptom dimensions were more severe in the OCD + TD group. CONCLUSION: Tic-related OCD may constitute a particular subgroup of the disorder with specific phenotypical characteristics, but its neurobiological underpinnings remain to be fully disentangled.
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Trastorno Obsesivo Compulsivo/complicaciones , Trastorno Obsesivo Compulsivo/epidemiología , Tics/complicaciones , Tics/epidemiología , Adulto , Brasil/epidemiología , Comorbilidad , Estudios Transversales , Femenino , Humanos , Masculino , Trastornos de Tic/epidemiologíaRESUMEN
A substantial number of patients with obsessive-compulsive disorder (OCD) report compulsions that are preceded not by obsessions but by subjective experiences known as sensory phenomena. This study aimed to investigate the frequency, severity, and age at onset of sensory phenomena in OCD, as well as to compare OCD patients with and without sensory phenomena in terms of clinical characteristics. We assessed 1,001 consecutive OCD patients, using instruments designed to evaluate the frequency/severity of OC symptoms, tics, anxiety, depression, level of insight and presence/severity of sensory phenomena. All together, 651 (65.0%) subjects reported at least one type of sensory phenomena preceding the repetitive behaviors. Considering the sensory phenomena subtypes, 371 (57.0%) patients had musculoskeletal sensations, 519 (79.7%) had externally triggered "just-right" perceptions, 176 (27.0%) presented internally triggered "just right," 144 (22.1%) had an "energy release," and 240 (36.9%) patients had an "urge only" phenomenon. Sensory phenomena were described as being as more severe than were obsessions by 102(15.7%) patients. Logistic regression analysis showed that the following characteristics were associated with the presence of sensory phenomena: higher frequency and greater severity of the symmetry/ordering/arranging and contamination/washing symptom dimensions; comorbid Tourette syndrome, and a family history of tic disorders. These data suggest that sensory phenomena constitute a poorly understood psychopathological aspect of OCD that merits further investigation.
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Trastorno Obsesivo Compulsivo/psicología , Percepción , Trastornos de Tic/psicología , Síndrome de Tourette/psicología , Adolescente , Adulto , Edad de Inicio , Ansiedad/complicaciones , Ansiedad/tratamiento farmacológico , Ansiedad/psicología , Niño , Depresión/complicaciones , Depresión/tratamiento farmacológico , Depresión/psicología , Femenino , Humanos , Masculino , Trastorno Obsesivo Compulsivo/complicaciones , Trastorno Obsesivo Compulsivo/tratamiento farmacológico , Escalas de Valoración Psiquiátrica , Índice de Severidad de la Enfermedad , Trastornos de Tic/complicaciones , Trastornos de Tic/tratamiento farmacológico , Síndrome de Tourette/complicaciones , Síndrome de Tourette/tratamiento farmacológicoRESUMEN
Obsessive-compulsive disorder (OCD) is a prevalent psychiatric disorder of unknown etiology. However, there is some evidence that the immune system may play an important role in its pathogenesis. In the present study, two polymorphisms (rs1800795 and rs361525) in the promoter region of the cytokine tumor necrosis factor-alpha (TNFA) gene were genotyped in 183 OCD patients and in 249 healthy controls. The statistical tests were performed using the PLINK(®) software. We found that the A allele of the TNFA rs361525 polymorphism was significantly associated with OCD subjects, according to the allelic χ(2) association test (p=0.007). The presence of genetic markers, such as inflammatory cytokines genes linked to OCD, may represent additional evidence supporting the role of the immune system in its pathogenesis.
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Trastorno Obsesivo Compulsivo/genética , Polimorfismo Genético/genética , Factor de Necrosis Tumoral alfa/genética , Estudios de Casos y Controles , Frecuencia de los Genes , Marcadores Genéticos , Predisposición Genética a la Enfermedad , HumanosRESUMEN
Obsessive-compulsive disorder (OCD) is a prevalent psychiatric disorder of unknown etiology. However, there is some evidence that the immune system may play an important role in its pathogenesis. In the present study, two polymorphisms (rs1800795 and rs361525) in the promoter region of the cytokine tumor necrosis factor-alpha (TNFA) gene were genotyped in 183 OCD patients and in 249 healthy controls. The statistical tests were performed using the PLINK® software. We found that the A allele of the TNFA rs361525 polymorphism was significantly associated with OCD subjects, according to the allelic χ² association test (p=0.007). The presence of genetic markers, such as inflammatory cytokines genes linked to OCD, may represent additional evidence supporting the role of the immune system in its pathogenesis.
O transtorno obsessivo-compulsivo (TOC) é um quadro psiquiátrico de prevalência considerável na população e de etiologia desconhecida. No entanto, há evidências de que o sistema imunológico pode desempenhar um papel importante em sua patogênese. No presente estudo, dois polimorfismos (rs1800795 e rs361525), localizados na região promotora do gene que codifica a citocina conhecida como fator de necrose tumoral alfa (TNFA), foram genotipados em 183 pacientes com TOC e 249 controles saudáveis. Os testes estatísticos foram realizados utilizando-se o software PLINK®. Assim, evidenciou-se que o alelo A do polimorfismo rs361525 apresentava associação estatisticamente significante com o TOC (p=0,007). A presença de marcadores genéticos, tais como genes que codificam citocinas inflamatórias, associados com TOC, confere suporte adicional ao papel do sistema imunológico na patogênese desse transtorno.
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Humanos , Trastorno Obsesivo Compulsivo/genética , Polimorfismo Genético/genética , Factor de Necrosis Tumoral alfa/genética , Estudios de Casos y Controles , Frecuencia de los Genes , Marcadores Genéticos , Predisposición Genética a la EnfermedadRESUMEN
INTRODUCTION: Obsessive-compulsive disorder (OCD) is a heterogeneous condition, in which subtypes have been proposed. Previous studies suggested that gender plays a relevant role in OCD phenotypic expression. This study aimed to review the literature on gender differences in clinical, genetic or familial aspects of OCD. METHOD: A conventional review was conducted, including all papers that investigated demographic, clinical, and genetic aspects of OCD according to gender. The search was based on data available in Medline and PsycINFO databases in the last 20 years, using as keywords: obsessive-compulsive disorder; and: gender, sex, male, female, demographic characteristics, clinical features, clinical characteristics, genetic, genes, genetics gender OCD, genes OCD, genes OCD males, genes OCD females. RESULTS: Sixty three of 487 phenotypical and genetics studies were selected. Most studies indicate that male patients are more likely than females to be single, present early onset of symptoms and chronic course of the disorder, greater social impairment, more sexual-religious and aggressive symptoms, and greater comorbidity with tic and substance use disorders. Female patients present more contamination/cleaning symptoms and greater comorbidity with eating and impulse-control disorders. Genetic and family studies are inconclusive, but suggest that gender may play a role in the disease expression. CONCLUSIONS: Gender is a relevant factor that should be taken into account when evaluating OCD patients. More studies are necessary to determine whether in fact it defines a homogeneous and particular group in OCD.
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Trastorno Obsesivo Compulsivo/genética , Factores Sexuales , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Trastorno Obsesivo Compulsivo/psicología , Fenotipo , Factores SocioeconómicosRESUMEN
INTRODUCTION: Obsessive-compulsive disorder (OCD) is a heterogeneous condition, in which subtypes have been proposed. Previous studies suggested that gender plays a relevant role in OCD phenotypic expression. This study aimed to review the literature on gender differences in clinical, genetic or familial aspects of OCD. METHOD: A conventional review was conducted, including all papers that investigated demographic, clinical, and genetic aspects of OCD according to gender. The search was based on data available in Medline and PsycINFO databases in the last 20 years, using as keywords: obsessive-compulsive disorder; and: gender, sex, male, female, demographic characteristics, clinical features, clinical characteristics, genetic, genes, genetics gender OCD, genes OCD, genes OCD males, genes OCD females. RESULTS: Sixty three of 487 phenotypical and genetics studies were selected. Most studies indicate that male patients are more likely than females to be single, present early onset of symptoms and chronic course of the disorder, greater social impairment, more sexual-religious and aggressive symptoms, and greater comorbidity with tic and substance use disorders. Female patients present more contamination/cleaning symptoms and greater comorbidity with eating and impulse-control disorders. Genetic and family studies are inconclusive, but suggest that gender may play a role in the disease expression. CONCLUSIONS: Gender is a relevant factor that should be taken into account when evaluating OCD patients. More studies are necessary to determine whether in fact it defines a homogeneous and particular group in OCD.
INTRODUÇÃO: O transtorno obsessivo-compulsivo (TOC) é um quadro heterogêneo, no qual subtipos têm sido propostos. Estudos anteriores sugerem que gênero desempenha papel relevante na expressão fenotípica. O objetivo foi realizar uma revisão convencional da literatura sobre diferenças de gênero em relação a aspectos clínicos e genéticos ou familiares do TOC. MÉTODO: Realizou-se uma revisão convencional da literatura incluindo todos os artigos que investigaram aspectos sociodemográficos, clínicos e genéticos do TOC, de acordo com o gênero. A pesquisa foi baseada em publicações disponíveis nas bases de dados Medline e PsycInfo nos últimos 20 anos, usando como palavras-chave: obsessive-compulsive disorder (OCD), e: gender, sex, male, female, demographic characteristics, clinical features, clinical characteristics, genetic, genes, genetics gender OCD, genes OCD, genes OCD males, genes OCD females. RESULTADO: Sessenta e três artigos de fenótipo e genética foram selecionados. Na maioria dos estudos, o sexo masculino associou-se mais que o feminino com: ser solteiro, apresentar início mais precoce dos sintomas, maior prejuízo social, mais sintomas sexuais, religiosos e de agressão, e mais comorbidade com transtorno de tiques e abuso de substâncias. Pacientes do sexo feminino apresentam mais sintomas de contaminação/limpeza e mais comorbidade com transtornos alimentares e do controle de impulsos. Estudos genéticos e familiares são controversos, mas indicam que o gênero pode desempenhar um papel na expressão da doença. CONCLUSÃO: Gênero é um fator relevante a ser considerado na avaliação de pacientes com TOC. São necessários mais estudos para determinar se este fator define de fato um grupo homogêneo e particular de TOC.
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Femenino , Humanos , Masculino , Trastorno Obsesivo Compulsivo/genética , Factores Sexuales , Predisposición Genética a la Enfermedad , Trastorno Obsesivo Compulsivo/psicología , Fenotipo , Factores SocioeconómicosRESUMEN
INTRODUÇÃO: Muitos estudos têm investigado a associação do polimorfismo VNTR (número variável de repetições em série) localizado na região promotora do gene da enzima monoamina oxidase A (MAOA) com alterações no comportamento humano e em diversos transtornos psiquiátricos. OBJETIVO: O objetivo do presente trabalho foi revisar a literatura sobre a participação desse polimorfismo funcional na modulação do comportamento humano para o desenvolvimento dos transtornos psiquiátricos. MÉTODO: A pesquisa foi realizada na literatura em inglês, de janeiro de 1998 a junho de 2009, disponível no Medline, Embase, Web of Science e na base de dados PsycInfo, utilizando os seguintes termos: "MAOA e comportamento humano" e "MAOA e psiquiatria". RESULTADOS: Foram encontrados 3.873 estudos. Desses, 109 foram selecionados e incluídos na revisão. Encontrou-se associação de alelos de baixa atividade do VNTR com transtorno de personalidade antissocial, transtorno de conduta, transtorno de déficit de atenção e hiperatividade, jogo patológico e dependência de substâncias. Alelos da alta atividade da MAOA foram associados a depressão, ansiedade, neuroticismo e anorexia nervosa. Não se encontrou associação entre polimorfismos da MAOA e esquizofrenia e transtorno bipolar. CONCLUSÃO: Os principais achados dão suporte ao papel do polimorfismo VNTR da região promotora do gene da MAOA em alguns transtornos psiquiátricos, apesar das divergências encontradas devidas às dificuldades metodológicas de estudos em genética. De modo geral, os estudos associam os alelos de baixa atividade da MAOA com comportamentos impulsivos e agressivos ("comportamentos hiperativos"), enquanto os alelos de alta atividade do gene são mais associados a "comportamentos hipoativos".
INTRODUCTION: A functional variable number of tandem repeats (VNTR) polymorphism of the promoter region of the monoamine oxidase A (MAOA) gene has been described and many studies have investigated the association of this polymorphism with human behaviors, as well as with several psychiatric disorders. OBJECTIVE: This study aimed to review the literature on the role of the VNTR functional polymorphism of the promoter region of the MAOA gene on the modulation of human behavior for the development of psychiatric disorders. METHOD: Searches on the Medline, Embase, Web of Science and PsycInfo databases were performed including works from January 1998 to June 2009. The words used were: "MAOA and human behavior" and "MAOA and psychiatry". RESULTS: Several studies were found (N = 3,873). After the selection process, 109 papers were included in the review. There was found an association of MAOA low activity alleles with antisocial personality disorder, conduct disorder, ADHD, pathological gambling, and substance abuse. High activity alleles were associated with neuroticism, anorexia nervosa and depression and anxiety disorders. There was no association between the MAOA polymorphisms and bipolar disorder and schizophrenia. DISCUSSION: The main findings, summarized in this paper, support a role of MAOA VNTR polymorphism in some psychiatric disorders although some divergences were found due to methodological difficulties in genetic studies. In general, the studies associated the low activity alleles with impulsivity and aggressive behavior ("hyperactive behaviors"), and the high activity alleles of the gene with "hypoactive behaviors", such as depression and anxiety, which demonstrates a modulation of the MAOA enzyme in "hyperactive" and "hypoactive" disorders.
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Conducta , Monoaminas Biogénicas , Polimorfismo Genético , Trastornos Mentales/genéticaRESUMEN
BACKGROUND: An impairing preoccupation with a nonexistent or slight defect in appearance is the core symptom of body dysmorphic disorder (BDD), a psychiatric condition common in dermatology settings. OBJECTIVE: We sought to determine the prevalence of BDD in dermatologic patients, comparing general and cosmetic settings, and describing some demographic and clinical characteristics. METHODS: In all, 300 patients were consecutively assessed. Screening and diagnoses were performed with validated instruments plus a best estimate diagnosis procedure. The final sample comprised 150 patients in the cosmetic group, 150 patients in the general dermatology group, and 50 control subjects. Standard statistical analyses were performed (chi(2), nonparametric tests, logistic regression). RESULTS: The current prevalence was higher in the cosmetic group (14.0%) compared with general (6.7%) and control (2.0%) groups. No patient had a previous diagnosis. Frequently the reason for seeking dermatologic treatment was not the main BDD preoccupation. Patients with BDD from the cosmetic group were in general unsatisfied with the results of dermatologic treatments. LIMITATIONS: Cross-sectional study conducted in a university hospital is a limitation. It is uncertain if the findings can be generalized. Retrospective data regarding previous treatments are not free from bias. CONCLUSIONS: BDD is relatively common in a dermatologic setting, especially among patients seeking cosmetic treatments. These patients have some different features compared with general dermatology patients. Dermatologists should be aware of the clinical characteristics of BDD to identify and refer these patients to mental health professionals.
Asunto(s)
Trastorno Dismórfico Corporal/epidemiología , Trastorno Dismórfico Corporal/psicología , Imagen Corporal , Enfermedades de la Piel/epidemiología , Enfermedades de la Piel/psicología , Adulto , Brasil/epidemiología , Técnicas Cosméticas/psicología , Técnicas Cosméticas/estadística & datos numéricos , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Enfermedades de la Piel/terapia , Cirugía Plástica/psicología , Cirugía Plástica/estadística & datos numéricos , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To describe a protocol that was based on an integrative neurobiological model of scientific investigation to better understand the pathophysiology of obsessive-compulsive disorder and to present the clinical and demographic characteristics of the sample. METHOD: A standardized research protocol that combines different methods of investigation (genetics, neuropsychology, morphometric magnetic resonance imaging and molecular neuroimaging of the dopamine transporter) obtained before and after treatment of drug-naïve adult obsessive-compulsive disorder patients submitted to a sequentially allocated 12-week clinical trial with a selective serotonin reuptake inhibitor (fluoxetine) and group cognitive-behavioral therapy. RESULTS: Fifty-two treatment-naïve obsessive-compulsive disorder patients entered the clinical trial (27 received fluoxetine and 25 received group cognitive-behavioral therapy). At baseline, 47 blood samples for genetic studies, 50 neuropsychological evaluations, 50 morphometrical magnetic resonance images and 48 TRODAT-1 single-photon emission computed tomography (SPECT) exams were obtained. After 12 weeks, 38 patients completed the protocol (fluoxetine = 20 and GCBT = 18). Thirty-eight neuropsychological evaluations, 31 morphometrical magnetic resonance images and 34 TRODAT-1 SPECT exams were obtained post-treatment. Forty-one healthy controls matched for age, gender, socioeconomic status, level of education and laterality were submitted to the same research procedures at baseline. CONCLUSION: The comprehensive treatment response protocol applied in this project allowing integration on genetic, neuropsychological, morphometrical and molecular imaging of the dopamine transporter data in drug-naïve patients has the potential to generate important original information on the neurobiology of obsessive-compulsive disorder, and at the same time be clinically meaningful.
OBJETIVO: Descrever um protocolo integrativo de investigação neurobiológica para melhor compreender as bases patofisiológicas do transtorno obsessivo-compulsivo e apresentar as características clínicas e demográficas da amostra. MÉTODO: Protocolo padronizado que combina diferentes modalidades de investigação (genética, neuropsicologia, ressonância magnética cerebral e imagem molecular do transportador de dopamina) obtidas antes e depois do tratamento em pacientes com transtorno obsessivo-compulsivo nunca expostos à medicação submetidos a um ensaio clínico comparando um inibidor seletivo da recaptação de serotonina (fluoxetina) e terapia cognitivo-comportamental em grupo. RESULTADOS: Cinquenta e dois pacientes com transtorno obsessivo-compulsivo entraram no ensaio clínico (27 no grupo fluoxetina e 25 no grupo de terapia). No início, foram realizadas 47 coletas de sangue para genética, 50 avaliações neuropsicológicas, 50 ressonâncias magnéticas cerebrais e 48 exames de tomografia computadorizada por emissão de fóton único (SPECT) com TRODAT-1. Depois de 12 semanas, 38 pacientes terminaram o protocolo (20 no grupo de fluoxetina e 18 no grupo de terapia). Trinta e oito reavaliações neuropsicológicas, 31 ressonâncias magnéticas de crânio e 34 exames de SPECT foram obtidos após o tratamento. Quarenta e um controles pareados foram submetidos ao mesmo protocolo inicial. CONCLUSÃO: Os dados genéticos, neuropsicológicos, volumétricos e moleculares do transportador de dopamina aliados à resposta a tratamento podem tanto gerar informações importantes a respeito da neurobiologia do transtorno obsessivo-compulsivo quanto ter uma aplicação clínica.
Asunto(s)
Adolescente , Adulto , Anciano , Humanos , Persona de Mediana Edad , Adulto Joven , Terapia Cognitivo-Conductual , Fluoxetina/uso terapéutico , Trastorno Obsesivo Compulsivo/terapia , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Imagen por Resonancia Magnética , Imagen Molecular , Trastorno Obsesivo Compulsivo/fisiopatología , Tomografía Computarizada de Emisión de Fotón Único , Resultado del TratamientoRESUMEN
INTRODUCTION: Although obsessions and compulsions comprise the main features of obsessive-compulsive disorder (OCD), many patients report that their compulsions are preceded by a sense of "incompleteness" or other unpleasant feelings such as premonitory urges or a need perform actions until feeling "just right." These manifestations have been characterized as Sensory Phenomena (SP). The current study presents initial psychometric data for a new scale designed to measure SP. METHODS: Seventy-six adult OCD subjects were probed twice. Patients were assessed with an open clinical interview (considered as the "gold standard") and with the following standardized instruments: Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I Disorders, Yale-Brown Obsessive-Compulsive Scale, Dimensional Yale-Brown Obsessive-Compulsive Scale, Yale Global Tic Severity Scale, Beck Anxiety Inventory, and Beck Depression Inventory. RESULTS: SP were present in 51 OCD patients (67.1%). Tics were present in 16 (21.1%) of the overall sample. The presence of SP was significantly higher in early-onset OCD patients. There were no significant differences in the presence of SP according to comorbidity with tics or gender. The comparison between the results from the open clinical interviews and the University of São Paulo Sensory Phenomena Scale (USP-SPS) showed an excellent concordance between them, with no significant differences between interviewers. The inter-rater reliability between the expert raters for the USP-SPS was high, with K=.92. The Pearson correlation coefficient between the SP severity scores given by the two raters was .89. CONCLUSION: Preliminary results suggest that the USP-SPS is a valid and reliable instrument for assessing the presence and severity of SP in OCD subjects.
Asunto(s)
Emociones/fisiología , Trastorno Obsesivo Compulsivo/psicología , Percepción/fisiología , Psicometría/métodos , Psicometría/normas , Sensación , Adulto , Edad de Inicio , Brasil , Distribución de Chi-Cuadrado , Femenino , Humanos , Masculino , Trastorno Obsesivo Compulsivo/diagnóstico , Escalas de Valoración Psiquiátrica , Estudios Retrospectivos , Universidades , Adulto JovenRESUMEN
OBJECTIVE: Evidence from family and molecular genetic studies support the hypothesis of involvement of immunologic mechanisms in the pathophysiology of obsessive-compulsive disorder. The nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-like 1 (NFKBIL1) has been suggested as a modulator of the immunological system. Given the importance of NFKBIL1 in the immunological response, the present study investigated the -62A/T polymorphism (rs2071592), located in the promoter region of its gene (NFKBIL1), as a genetic risk factor for the development of obsessive-compulsive disorder. METHOD: The -62A/T NFKBIL1 polymorphism was investigated in a sample of 111 patients who met DSM-IV criteria for obsessive-compulsive disorder and 272 healthy age- and gender-matched controls. RESULTS: There were no differences in genotypic distributions between patients and controls (chi2 = 0.98; 2 d.f.; p = 0.61). DISCUSSION: Despite these negative findings, more comprehensive polymorphism coverage within the NFKBIL1 is warranted in larger samples. Populations with different ethnic backgrounds should also be studied. CONCLUSION: The results of the present investigation do not provide evidence for the association between the -62A/T NFKBIL1 polymorphism and obsessive-compulsive disorder in this Brazilian sample.
Asunto(s)
Antígenos de Histocompatibilidad Clase II/genética , Trastorno Obsesivo Compulsivo/genética , Polimorfismo Genético , Proteínas Adaptadoras Transductoras de Señales , Adulto , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , MasculinoRESUMEN
OBJECTIVE: Evidence from family and molecular genetic studies support the hypothesis of involvement of immunologic mechanisms in the pathophysiology of obsessive-compulsive disorder. The nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-like 1 (NFKBIL1) has been suggested as a modulator of the immunological system. Given the importance of NFKBIL1 in the immunological response, the present study investigated the -62A/T polymorphism (rs2071592), located in the promoter region of its gene (NFKBIL1), as a genetic risk factor for the development of obsessive-compulsive disorder. METHOD: The -62A/T NFKBIL1 polymorphism was investigated in a sample of 111 patients who met DSM-IV criteria for obsessive-compulsive disorder and 272 healthy age- and gender-matched controls. RESULTS: There were no differences in genotypic distributions between patients and controls (χ2 = 0.98; 2 d.f.; p = 0.61). DISCUSSION: Despite these negative findings, more comprehensive polymorphism coverage within the NFKBIL1 is warranted in larger samples. Populations with different ethnic backgrounds should also be studied. CONCLUSION: The results of the present investigation do not provide evidence for the association between the -62A/T NFKBIL1 polymorphism and obsessive-compulsive disorder in this Brazilian sample.
OBJETIVO: Evidências advindas de estudos de família e de genética molecular têm dado suporte à hipótese do envolvimento de mecanismos imunológicos na fisiopatologia do transtorno obsessivo-compulsivo. Tem sido sugerido que o potencializador do fator nuclear do polipeptídeo kappa light em células-B inibidoras-like 1 (NFKBIL1) é um modulador do sistema imunológico. Dada a importância do NFKBIL1 na resposta imunológica, o presente estudo investigou o polimorfismo -62A/T (rs2071592), localizado na região promotora de seu gene, como fator de risco genético para o desenvolvimento do transtorno obsessivo-compulsivo. MÉTODO: O polimorfismo -62A/T do gene do NFKBIL1 foi investigado em uma amostra de 111 pacientes com o diagnóstico de transtorno obsessivo-compulsivo, de acordo com os critérios do DSM-IV, e 272 controles saudáveis emparelhados por idade e gênero. RESULTADOS: Não houve diferenças na distribuição genotípica entre pacientes e controles (χ2 = 0,98; 2 d.f.; p = 0,61). DISCUSSÃO: Apesar dos resultados negativos, estudos compreendendo mais polimorfismos no gene do NFKBIL, em amostras maiores, são necessários. Populações com diferentes origens étnicas também precisam ser avaliadas. CONCLUSÃO: Os resultados da presente investigação não evidenciam associação entre o polimorfismo -62A/T do gene do NFKBIL1 e o transtorno obsessivo-compulsivo nesta amostra brasileira.