Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders guidelines for the treatment of adult obsessive-compulsive disorder. Part I: pharmacological treatment

Objectives: To summarize evidence-based pharmacological treatments and provide guidance on clinical interventions for adult patients with obsessive-compulsive disorder (OCD). Methods: The American Psychiatric Association (APA) guidelines for the treatment of OCD (2013) were updated with a systematic review assessing the efficacy of pharmacological treatments for adult OCD, comprising monotherapy with selective serotonin reuptake inhibitors (SSRIs), clomipramine, serotonin and norepinephrine reuptake inhibitors (SNRIs), and augmentation strategies with clomipramine, antipsychotics, and glutamate-modulating agents. We searched for the literature published from 2013-2020 in five databases, considering the design of the study, primary outcome measures, types of publication, and language. Selected articles had their quality assessed with validated tools. Treatment recommendations were classified according to levels of evidence developed by the American College of Cardiology and the American Heart Association (ACC/AHA). Results: We examined 57 new studies to update the 2013 APA guidelines. High-quality evidence supports SSRIs for first-line pharmacological treatment of OCD. Moreover, augmentation of SSRIs with antipsychotics (risperidone, aripiprazole) is the most evidence-based pharmacological intervention for SSRI-resistant OCD. Conclusion: SSRIs, in the highest recommended or tolerable doses for 8-12 weeks, remain the first-line treatment for adult OCD. Optimal augmentation strategies for SSRI-resistant OCD include low doses of risperidone or aripiprazole. Pharmacological treatments considered ineffective or potentially harmful, such as monotherapy with antipsychotics or augmentation with ketamine, lamotrigine, or N-acetylcysteine, have also been detailed.

The impact of the environment on neurodevelopmental disorders in early childhood

Abstract Objectives: To review the literature about the environmental impact on children's mental, behavior, and neurodevelopmental disorders. Sources of data: A nonsystematic review of papers published on MEDLINE-PubMed was carried out using the terms environment and mental health or psychiatric disorders or neurodevelopmental disorders. Summary of findings: Psychopathology emerges at different developmental times as the outcome of complex interactions between nature and nurture and may impact each person in different ways throughout childhood and determine adult outcomes. Mental health is intertwined with physical health and is strongly influenced by cultural, social and economic factors. The worldwide prevalence of psychiatric disorders in children and adolescents is 13.4%, and the most frequent are anxiety, disruptive behavior disorders, attention deficit hyperactivity disorder and depression. Neurodevelopment begins at the embryonic stage and continues through adulthood with genetic differences, environmental exposure, and developmental timing acting synergistically and contingently. Early life experiences have been linked to a dysregulation of the neuroendocrine-immune circuitry which results in alterations of the brain during sensitive periods. Also, the environment may trigger modifications on the epigenome of the differentiating cell, leading to changes in the structure and function of the organs. Over 200 million children under 5 years are not fulfilling their developmental potential due to the exposure to multiple risk factors, including poverty, malnutrition and unsafe home environments. Conclusions: Continued support for the promotion of a protective environment that comprises effective parent-child interactions is key in minimizing the effects of neurodevelopmental disorders throughout the lifetime.

Measuring child maltreatment using multi-informant survey data: a higher-order confirmatory factor analysis / Dados de levantamento com múltiplos informantes para a mensuração de maus-tratos na infância: uma análise fatorial confirmatória de segunda ordem

Objective To investigate the validity and reliability of a multi-informant approach to measuring child maltreatment (CM) comprising seven questions assessing CM administered to children and their parents in a large community sample. Methods Our sample comprised 2,512 children aged 6 to 12 years and their parents. Child maltreatment (CM) was assessed with three questions answered by the children and four answered by their parents, covering physical abuse, physical neglect, emotional abuse and sexual abuse. Confirmatory factor analysis was used to compare the fit indices of different models. Convergent and divergent validity were tested using parent-report and teacher-report scores on the Strengths and Difficulties Questionnaire. Discriminant validity was investigated using the Development and Well-Being Assessment to divide subjects into five diagnostic groups: typically developing controls (n = 1,880), fear disorders (n = 108), distress disorders (n = 76), attention deficit hyperactivity disorder (n = 143) and oppositional defiant disorder/conduct disorder (n = 56). Results A higher-order model with one higher-order factor (child maltreatment) encompassing two lower-order factors (child report and parent report) exhibited the best fit to the data and this model's reliability results were acceptable. As expected, child maltreatment was positively associated with measures of psychopathology and negatively associated with prosocial measures. All diagnostic category groups had higher levels of overall child maltreatment than typically developing children. Conclusions We found evidence for the validity and reliability of this brief measure of child maltreatment using data from a large survey combining information from parents and their children.

Objetivo Investigar a validade e confiabilidade de uma abordagem de múltiplos informantes para a mensuração de maus-tratos na infância, composta por sete questões avaliando maus-tratos na infância respondidas pelas crianças e seus pais em uma ampla amostra comunitária. Métodos A amostra foi composta por 2.512 crianças com idades entre 6 e 12 anos e seus pais. Maus-tratos na infância foram avaliados com três questões respondidas pelas crianças e quatro respondidas pelos seus pais, investigando violência física, negligência física, violência emocional e violência sexual. Análises fatoriais confirmatórias foram utilizadas para comparar os índices de ajuste de diferentes modelos. Validade convergente e divergente foi testada utilizando escores de relato parental e de relato dos professores no Strengths and Difficulties Questionnaire. Validade discriminante foi investigada utilizando a entrevista Development and Well-Being Assessment para dividir os participantes em cinco grupos diagnósticos: controles com desenvolvimento típico (n = 1.880), transtornos do medo (n = 108), transtornos do estresse (n = 76), transtorno de déficit de atenção-hiperatividade (n = 143) e transtorno opositivo-desafiador/conduta (n = 56). Resultados Um modelo de segunda ordem com um fator de segunda ordem (maus-tratos na infância) englobando dois fatores de primeira ordem (relato da criança e relato parental) demonstrou o melhor ajuste aos dados, e os resultados de confiabilidade desse modelo foram aceitáveis. Como esperado, maus-tratos na infância estiveram positivamente associados a medidas de psicopatologia e negativamente associados a medidas pró-sociais. Todos os grupos de categorias diagnósticas tiveram níveis mais altos de maus-tratos na infância do que as crianças com desenvolvimento típico. Conclusões Foram encontradas evidências de validade e confiabilidade dessa medida breve de maus-tratos na infância utilizando dados de um grande levantamento combinando o relato de pais e seus filhos.

Methylphenidate use in children with attention deficit hyperactivity disorder / Uso de metilfenidato em crianças com transtorno de déficit de atenção e hiperatividade

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.

Pediatric anxiety disorders: from neuroscience to evidence-based clinical practice

The objective of this narrative review of the literature is to describe the epidemiology, etiology, pathophysiology, diagnosis, and treatment of pediatric anxiety disorders. We aim to guide clinicians in understanding the biology of anxiety disorders and to provide general guidelines for the proper diagnoses and treatment of these conditions early in life. Anxiety disorders are prevalent, associated with a number of negative life outcomes, and currently under-recognized and under-treated. The etiology involves both genes and environmental influences modifying the neural substrate in a complex interplay. Research on pathophysiology is still in its infancy, but some brain regions, such as the amygdala and the prefrontal cortex, have been implicated in fear and anxiety. Current practice is to establish diagnosis based purely on clinical features, derived from clinical interviews with the child, parents, and teachers. Treatment is effective using medication, cognitive behavioral therapy, or a combination of both. An introduction to the neuroscience behind anxiety disorders combined with an evidence-based approach may help clinicians to understand these disorders and treat them properly in childhood.

Estudos de associação genética no transtorno obsessivo-compulsivo / Genetic association studies in obsessive-compulsive disorder

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.

Performance of a Brazilian sample on the computerized Wisconsin Card Sorting Test

The computerized version of the Wisconsin Card Sorting Test (WCST) is based on the same normative data developed previously for the manual version. However, equivalence of the measures of both versions is controversial. This study investigated the performance of a Brazilian student sample with subjects aged 6-15 years in the computerized version of the WCST. As a result of the analyses, the study pointed out that type of school (public or private) was significant in almost all measures and also that age and gender effects were similar to those previously described in the manual version. These results showed that the computerized WCST may not be free of cultural and socioeconomic influences and that the validation and standardization of this version is warranted.

Influence of specific obsessive-compulsive symptom dimensions on strategic planning in patients with obsessive-compulsive disorder / Avaliação de planejamento estratégico em pacientes com transtorno obsessivo-compulsivo de acordo com as dimensões de sintomas obsessivo-compulsivos

OBJECTIVE: This study investigates obsessive-compulsive disorder patients in terms of strategic planning and its association with specific obsessive-compulsive symptom dimensions. METHOD: We evaluated 32 obsessive-compulsive disorder patients. Strategic planning was assessed by the Rey-Osterrieth Complex Figure Test, and the obsessive-compulsive dimensions were assessed by the Dimensional Yale-Brown Obsessive-Compulsive Scale. In the statistical analyses, the level of significance was set at 5 percent. We employed linear regression, including age, intelligence quotient, number of comorbidities, the Yale-Brown Obsessive-Compulsive Scale score, and the Dimensional Yale-Brown Obsessive-Compulsive Scale. RESULTS: The Dimensional Yale-Brown Obsessive-Compulsive Scale "worst-ever" score correlated significantly with the planning score on the copy portion of the Rey-Osterrieth Complex Figure Test (r = 0.4, p = 0.04) and was the only variable to show a significant association after linear regression (β = 0.55, t = 2.1, p = 0.04). Compulsive hoarding correlated positively with strategic planning (r = 0.44, p = 0.03). None of the remaining symptom dimensions presented any significant correlations with strategic planning. CONCLUSION: We found the severity of obsessive-compulsive symptoms to be associated with strategic planning. In addition, there was a significant positive association between the planning score on the copy portion of the Rey-Osterrieth Complex Figure Test copy score and the hoarding dimension score on the Dimensional Yale-Brown Obsessive-Compulsive Scale. Our results underscore the idea that obsessive-compulsive disorder is a heterogeneous disorder and suggest that the hoarding dimension has a specific neuropsychological profile. Therefore, it is important to assess the peculiarities of each obsessive-compulsive symptom dimension.

OBJETIVO: Este estudo investiga o planejamento estratégico em pacientes com transtorno obsessivo-compulsivo e sua possível associação com dimensões de sintomas obsessivo-compulsivos. MÉTODO: Foram avaliados 32 pacientes com transtorno obsessivo-compulsivo. O planejamento estratégico foi avaliado pelo Teste da Figura Complexa de Rey. Presença e gravidade de sintomas obsessivo-compulsivos foram avaliadas pela Escala Dimensional para Sintomas Obsessivo-Compulsivos e a Yale-Brown Obsessive-Compulsive Scale. Análises estatísticas foram realizadas utilizando nível de significância de 5 por cento. RESULTADOS: Escores globais da Escala Dimensional para Sintomas Obsessivo-Compulsivos na pior fase apresentaram correlação significativa com os escores de cópia do Teste da Figura Complexa de Rey-Osterrieth (r = 0,4, p = 0,04), além de manter significância na análise de regressão, incluindo idade, quociente de inteligência, número de comorbidades e escores no Yale-Brown Obsessive-Compulsive Scale e Escala Dimensional para Sintomas Obsessivo-Compulsivos (β= 0,55, t = 2,1, p = 0,04). A dimensão colecionismo teve uma correlação significativa com o escore de planejamento estratégico (r = 0,44, p = 0,03). As outras dimensões de sintomas obsessivo-compulsivos não apresentaram correlações significativas com os escores de planejamento estratégico. CONCLUSÃO: A gravidade dos sintomas obsessivo-compulsivos e a dimensão colecionismo apresentaram associações significativas com escores de planejamento estratégico na cópia do Teste da Figura Complexa de Rey. Os achados reforçam a ideia de que o transtorno obsessivo-compulsivo é um transtorno heterogêneo, e de que é importante avaliar as especificidades de cada dimensão de sintomas obsessivo-compulsivos, além de sugerir que a dimensão colecionismo apresenta características neuropsicológicas distintas.

O papel do polimorfismo funcional VNTR da região promotora do gene MAOA nos transtornos psiquiátricos / The role of the VNTR functional polymorphism of the promoter region of the MAOA gene on psychiatric disorders

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.

The Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders: recruitment, assessment instruments, methods for the development of multicenter collaborative studies and preliminary results / Consórcio Brasileiro de Pesquisa em Transtornos do Espectro Obsessivo-Compulsivo: recrutamento, instrumentos de avaliação, métodos para o desenvolvimento de estudos colaborativos multicêntricos e resultados preliminares

OBJECTIVE: To describe the recruitment of patients, assessment instruments, implementation, methods and preliminary results of The Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders, which includes seven university sites. METHOD: This cross-sectional study included a comprehensive clinical assessment including semi-structured interviews (sociodemographic data, medical and psychiatric history, disease course and comorbid psychiatric diagnoses), and instruments to assess obsessive-compulsive (Yale-Brown Obsessive-Compulsive Scale and Dimensional Yale-Brown Obsessive-Compulsive Scale), depressive (Beck Depression Inventory) and anxious (Beck Anxiety Inventory) symptoms, sensory phenomena (Universidade de São Paulo Sensory Phenomena Scale), insight (Brown Assessment Beliefs Scale), tics (Yale Global Tics Severity Scale) and quality of life (Medical Outcome Quality of Life Scale Short-form-36 and Social Assessment Scale). The raters' training consisted of watching at least five videotaped interviews and interviewing five patients with an expert researcher before interviewing patients alone. The reliability between all leaders for the most important instruments (Structured Clinical Interview for DSM-IV, Dimensional Yale-Brown Obsessive-Compulsive Scale, Universidade de São Paulo Sensory Phenomena Scale) was measured after six complete interviews. RESULTS: Inter-rater reliability was 96 percent. By March 2008, 630 obsessive-compulsive disorder patients had been systematically evaluated. Mean age (±SE) was 34.7 (±0.51), 56.3 percent were female, and 84.6 percent Caucasian. The most prevalent obsessive compulsive symptom dimensions were symmetry and contamination. The most common comorbidities were major depression, generalized anxiety and social anxiety disorder. The most common DSM-IV impulsive control disorder was skin picking. CONCLUSION: The sample was composed mainly by Caucasian individuals, unmarried, with some kind...

OBJETIVO: Descrever o recrutamento de pacientes, instrumentos de avaliação, métodos para o desenvolvimento de estudos colaborativos multicêntricos e os resultados preliminares do Consórcio Brasileiro de Pesquisa em Transtornos do Espectro Obsessivo-Compulsivo, que inclui sete centros universitários. MÉTODO: Este estudo transversal incluiu entrevistas semi-estruturadas (dados sociodemográficos, histórico médico e psiquiátrico, curso da doença e diagnósticos psiquiátricos comórbidos) e instrumentos que avaliam os sintomas do transtorno obsessivo-compulsivo (Escala para Sintomas Obsessivo-Compulsivos de Yale-Brown e Escala Dimensional para Sintomas Obsessivo-Compulsivos de Yale-Brown), sintomas depressivos (Inventário de Depressão de Beck), sintomas ansiosos (Inventário de Ansiedade de Beck), fenômenos sensoriais (Escala de Fenômenos Sensoriais da Universidade de São Paulo), juízo crítico (Escala de Avaliação de Crenças de Brown), tiques (Escala de Gravidade Global de Tiques de Yale) e qualidade de vida (questionário genérico de avaliação de qualidade de vida, Medical Outcome Quality of Life Scale Short-form-36 e Escala de Avaliação Social). O treinamento dos avaliadores consistiu em assistir cinco entrevistas filmadas e entrevistar cinco pacientes junto com um pesquisador mais experiente, antes de entrevistar pacientes sozinhos. A confiabilidade entre todos os líderes de grupo para os instrumentos mais importantes (Structured Clinical Interview for DSM-IV, Dimensional Yale-Brown Obsessive-Compulsive Scale, Universidade de São Paulo Sensory Phenomena Scale ) foi medida após seis entrevistas completas. RESULTADOS: A confiabilidade entre avaliadores foi de 96 por cento. Até março de 2008, 630 pacientes com transtorno obsessivo-compulsivo tinham sido sistematicamente avaliados. A média de idade (±SE) foi de 34,7 (±0,51), 56,3 por cento eram do sexo feminino e 84,6 por cento caucasianos. Os sintomas obsessivo-compulsivos mais prevalentes foram...

Transtorno obsessivo-compulsivo em paciente com sindrome de Tourette e febre reumatica sem coreia de Sydenham

Os autores descrevem um caso inedito de transtorno obsessivo-compulsivo (TOC) em paciente com sindrome de Tourette (ST) e febre reumatica (FR) sem coreia de Sydenham (CS), com inicio dos tiques no comeco da infancia. Discutem os possiveis mecanismos fisiopatologicos implicados nessa associacao

Obsessive-compulsive disorder and Tourette Syndrome: is there a relationship?

The authors describe the main characteristics of Obsessive-Compulsive Disorder, the fourth most frequent psychiatric disease, and Tourette Syndrome. Considered completely separate disorders, there is growing scientific evidence that there is a connection between them. The authors present clinical, genetic and neuroimaging data reinforcing this idea, and call attention to the importance of research in this area, as they believe that the definition of more homogenous subgroups will facilitate the indentification of biological markers and predictors of treatment response.