Objectives: To summarize evidence-based cognitive-behavioral therapy (CBT) treatment and propose clinical interventions for adult patients with obsessive-compulsive disorder (OCD). Methods: The literature on CBT interventions for adult OCD, including BT and exposure and response prevention, was systematically reviewed to develop updated clinical guidelines for clinicians, providing comprehensive details about the necessary procedures for the CBT protocol. We searched the literature from 2013-2020 in five databases (PubMed, Cochrane, Embase, PsycINFO, and Lilacs) regarding study design, primary outcome measures, publication type, and language. Selected articles were assessed for quality with validated tools. Treatment recommendations were classified according to levels of evidence developed by the American College of Cardiology and the American Heart Association. Results: We examined 44 new studies used to update the 2013 American Psychiatric Association guidelines. High-quality evidence supports CBT with exposure and response prevention techniques as a first-line treatment for OCD. Protocols for Internet-delivered CBT have also proven efficacious for adults with OCD. Conclusion: High-quality scientific evidence supports the use of CBT with exposure and response prevention to treat adults with OCD.

Objectives: To provide practical norms for measuring depressive symptoms with the Patient Health Questionnaire 9 (PHQ-9) in Brazil through a state-of-the-art psychometrics analysis. Methods: We used a large representative dataset from the 2019 Brazilian National Health Survey (Pesquisa Nacional de Saúde – 2019), which included 90,846 Brazilian citizens. To assess scale structure, we assessed a unidimensional model using confirmatory factor analysis. Item response theory was used to characterize the distribution of depressive symptoms. Summed- and mean-based PHQ-9 scores were then linked using item response theory-based scores in generalized additive models. Finally, percentiles, T scores, and a newly developed score, called the decimal score (D score), were generated to describe PHQ-9 norms for the Brazilian population. Results: Confirmatory factor analysis revealed a good fit to the unidimensional model, being invariant to age and sex. Item response theory captured item-level information about the latent trait (reliable from 1 to 3 SDs above the mean). Brazilian norms were presented using summed scores, T scores, and D scores. Conclusion: This is the first study to determine Brazilian norms for the PHQ-9 among a large representative sample using robust psychometric tools. More precise PHQ-9 scores are now available and may be widely used in primary and specialized clinical care settings.

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.

Objectives: To provide practical norms for measuring depressive symptoms with the Patient Health Questionnaire 9 (PHQ-9) in Brazil through a state-of-the-art psychometrics analysis. Methods: We used a large representative dataset from the 2019 Brazilian National Health Survey (Pesquisa Nacional de Saúde – 2019), which included 90,846 Brazilian citizens. To assess scale structure, we assessed a unidimensional model using confirmatory factor analysis. Item response theory was used to characterize the distribution of depressive symptoms. Summed- and mean-based PHQ-9 scores were then linked using item response theory-based scores in generalized additive models. Finally, percentiles, T scores, and a newly developed score, called the decimal score (D score), were generated to describe PHQ-9 norms for the Brazilian population. Results: Confirmatory factor analysis revealed a good fit to the unidimensional model, being invariant to age and sex. Item response theory captured item-level information about the latent trait (reliable from 1 to 3 SDs above the mean). Brazilian norms were presented using summed scores, T scores, and D scores. Conclusion: This is the first study to determine Brazilian norms for the PHQ-9 among a large representative sample using robust psychometric tools. More precise PHQ-9 scores are now available and may be widely used in primary and specialized clinical care settings.

Objective: The Identifying Depression Early in Adolescence Risk Score (IDEA-RS) was recently developed in Brazil using data from the Pelotas 1993 Birth Cohort to estimate the individualized probability of developing depression in adolescence. This model includes 11 sociodemographic variables and has been assessed in longitudinal studies from four other countries. We aimed to test the performance of IDEA-RS in an independent, community-based, school-attending sample within the same country: the Brazilian High-Risk Cohort. Methods: Standard external validation, refitted, and case mix-corrected models were used to predict depression among 1442 youth followed from a mean age of 13.5 years at baseline to 17.7 years at follow-up, using probabilities calculated with IDEA-RS coefficients. Results: The area under the curve was 0.65 for standard external validation, 0.70 for the case mix-corrected model, and 0.69 for the refitted model, with discrimination consistently above chance for predicting depression in the new dataset. There was some degree of miscalibration, corrected by model refitting (calibration-in-the-large reduced from 0.77 to 0). Conclusion: IDEA-RS was able to parse individuals with higher or lower probability of developing depression beyond chance in an independent Brazilian sample. Further steps should include model improvements and additional studies in populations with high levels of subclinical symptoms to improve clinical decision making.

Abstract Introduction Most children/adolescents with disability live in low and middle-income countries and, worldwide, they are more likely to have mental health problems and achieve worse academic performance compared to those with typical development. Objective To assess whether Brazilian children/adolescents with four types of disabilities are more likely to have psychiatric disorders and educational deficits than children/adolescents with typical development. Method A multicenter cross-sectional study involving a school-based probabilistic sample of second to sixth graders (N = 1,674) from public schools in four Brazilian regions. The four types of disabilities (intellectual, visual, hearing, and motor) were assessed using the Ten Questions Questionnaire. Psychiatric disorders were measured with the Schedule for Affective Disorders/Schizophrenia for School-Age Children (K-SADS-PL), and academic performance was evaluated using the Teste de Desempenho Acadêmico – TDE (the academic performance test). Results A logistic regression model with cluster-robust errors identified the following statistically significant associations with three of the four types of disability (the exception was hearing). Intellectual disability was associated with anxiety (p < 0.01), depression (p < 0.01), attention deficit hyperactivity disorder (ADHD) (p < 0.001), school failure (p < 0.01), and poor academic performance (p < 0.01). Visual disability was associated with depression (p < 0.01). Motor disability was marginally associated with ADHD (p = 0.08). Conclusions Presence of disabilities (intellectual, visual, and motor) in children/adolescents was associated with psychiatric disorders, school failure, and academic performance. It is therefore important to identify presence of disabilities and plan and deliver specific interventions and specialized educational care for the needs presented by these children/adolescents. This is particularly important in low and middle-income countries, where these disabilities are frequent among children/adolescents.

Abstract Introduction We assessed the impact of polythetic conceptualizations of mental disorders on the validity and reliability of psychiatric diagnosis, with a specific focus on two levels of heterogeneity: phenomenological and pathophysiological. Objective We investigated this issue using attention deficit hyperactivity disorder (ADHD) as an example. Method We examined individuals from two samples enriched for psychopathology (n = 1 255 children in Porto Alegre and 1 257 children in São Paulo, Brazil). We conducted a series of data analyses to investigate phenomenological heterogeneity, including confirmatory factor analysis. We also investigated pathophysiological heterogeneity using symptom-level regressions between ADHD symptoms and four neurocognitive processes consistently linked to ADHD (working memory, inhibitory control, intra-subject variability in reaction times, and temporal processing). Lastly, we assessed the performance of polythetic systems for reliability testing inter-rater and test-rest reliability of two well-known symptomatic scales. Results Among the 116 200 possible combinations of symptoms to achieve DSM symptomatic threshold for categorical ADHD diagnosis, we found 173 combinations in the two independent samples, and only four were replicated in both samples (2.3%). We also found that the number of ADHD symptoms is a poor indicator of variation in the general ADHD latent trait. Overall, symptoms did not have specific profiles of associations with any of the neurocognitive processes. Reliability analyses revealed that increasing the number of items augments overall reliability of measurements. Discussion and conclusion Our findings illustrate both potential benefits and problems inherent to the polythetic system for ADHD. Implications for the search of mechanisms underlying psychiatric disorders are discussed.

Resumen Antecedentes Evaluamos el impacto de las conceptualizaciones politécnicas de los trastornos mentales en la validez y la fiabilidad del diagnóstico psiquiátrico, con un enfoque específico en dos niveles de heterogeneidad: fenomenológico y fisiopatológico. Objetivos Investigamos este problema utilizando el trastorno por déficit de atención e hiperactividad (TDAH) como ejemplo. Método Examinamos individuos de dos muestras enriquecidas por psicopatología (n = 1 255 niños en Porto Alegre y 1 257 niños en São Paulo, Brasil). Llevamos a cabo una serie de análisis de datos para investigar la heterogeneidad fenomenológica, incluido el análisis factorial confirmatorio. También investigamos la heterogeneidad fisiopatológica utilizando regresiones al nivel de síntomas entre los síntomas del TDAH y cuatro procesos neurocognitivos consistentemente vinculados al TDAH (memoria de trabajo, control inhibitorio, variabilidad intrasujeto en tiempos de reacción y procesamiento temporal). Por último, evaluamos el rendimiento de los sistemas politéticos para la prueba de confiabilidad interevaluador y la confiabilidad test-rest de dos escalas sintomáticas bien conocidas. Resultados Entre las 116 200 posibles combinaciones de síntomas para alcanzar el umbral sintomático del DSM para el diagnóstico categórico de TDAH, encontramos 173 combinaciones en las dos muestras independientes y sólo cuatro se replicaron en ambas muestras (2.3%). También encontramos que la cantidad de síntomas de TDAH no es un buen indicador de la variación en el rasgo latente general del TDAH. En general, los síntomas no tenían perfiles específicos de asociaciones con ninguno de los procesos neurocognitivos. Los análisis de confiabilidad revelaron que aumentar el número de artículos aumenta la confiabilidad general de las mediciones. Discusión y conclusión Nuestros hallazgos ilustran tanto los beneficios potenciales como los problemas inherentes al sistema politécnico para el TDAH. Se discuten las implicaciones para la búsqueda de mecanismos subyacentes a los trastornos psiquiátricos.

RESUMO CONTEXTO E OBJETIVO: Técnicas de neuromodulação para o tratamento do transtorno obsessivo compulsivo (TOC) vêm se expandindo com o melhor entendimento dos circuitos cerebrais envolvidos no transtorno. A estimulação transcraniana por corrente contínua (ETCC), uma técnica não invasiva, vem sendo estudada como alternativa para o TOC resistente aos tratamentos convencionais. Descrevemos o desenho de um ensaio clínico utilizando a ETCC para o TOC e relatamos os desfechos de dois pacientes com TOC primário resistentes à terapia cognitivo-comportamental e aos inibidores seletivos de recaptura da serotonina, que receberam ETCC de modo aberto durante a fase de treino dos procedimentos do estudo. TIPO DE ESTUDO E LOCAL: Descrição metodológica de um ensaio clínico utilizando ETCC para o TOC resistente num hospital universitário e relato de dois casos. MÉTODOS: O estudo proposto é randomizado, controlado por sham e duplo-cego. 44 pacientes serão randomizados para intervenção ativa ou simulada (sham ). A intervenção ativa consiste em aplicar uma corrente elétrica de 2 mA, com cátodo posicionado na região correspondente à área cortical motora suplementar (bilateralmente) e ânodo posicionado no deltoide. Desfecho primário: redução do escore inicial da escala YBOCS (Yale-Brown Obsessive Compulsive Scale) ao final da quarta semana. Desfechos secundários: sintomas depressivos e ansiosos. Marcadores genéticos, excitabilidade cortical e performance em testes neurocognitivos serão investigados. RESULTADOS: O primeiro paciente apresentou melhora significativa, enquanto o segundo permaneceu sintomático ao término das quatro semanas e após seis meses. A ETCC foi bem tolerada. CONCLUSÃO: A ETCC para o tratamento do TOC resistente merece ensaios clínicos randomizados que testem sua efetividade.

ABSTRACT CONTEXT AND OBJECTIVE: Neuromodulation techniques for treating obsessive-compulsive disorder (OCD) have expanded through greater understanding of the brain circuits involved in this disorder. Transcranial direct current stimulation (tDCS), a non-invasive technique, has been studied as an alternative for treatment-resistant OCD. We describe the design of a clinical trial using tDCS for OCD and report on the outcomes from two patients with primary OCD who were resistant to cognitive-behavioral therapy and to selective serotonin reuptake inhibitors, and who received tDCS in an open manner during the training phase for the study procedures. DESIGN AND SETTING: Methodological description of a clinical trial using tDCS for treatment-resistant OCD at a university hospital; and a report on two cases. METHODS: The proposed study is randomized, sham-controlled and double-blind. Forty-four patients will be randomized to either active or sham intervention. The active intervention consists of applying an electric current of 2 mA, with the cathode positioned in the region corresponding to the supplementary motor cortex (bilaterally) and the anode positioned in the deltoid. The primary outcome will be the reduction in baseline YBOCS (Yale-Brown Obsessive Compulsive Scale) score at the end of week 4. The secondary outcomes will be depression and anxiety symptoms. Genetic markers, cortical excitability and neurocognitive performance will be investigated. RESULTS: The first patient showed significant improvement, whereas the second remained symptomatic after four weeks and after six months. tDCS was well tolerated. CONCLUSION: tDCS for treatment-resistant OCD merits randomized controlled trials that test its effectiveness.

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.

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.

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.

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.

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.

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.

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.

OBJECTIVE: This paper aims to describe and discuss a minimization procedure specifically designed for a clinical trial that evaluates treatment efficacy for OCD patients. METHOD: Aitchison's compositional distance was used to calculate vectors for each possibility of allocation in a covariate adaptive method. Two different procedures were designed to allocate patients in small blocks or sequentially one-by-one. RESULTS: We present partial results of this allocation procedure as well as simulated data. In the clinical trial for which this procedure was developed, successful balancing between treatment arms was achieved. Separately, in an exploratory analysis, we found that if the arrival order of patients was altered, most patients were allocated to a different treatment arm than their original assignment. CONCLUSION: Our results show that the random arrival order of patients determine different assignments and therefore maintains the unpredictability of the allocation method. We conclude that our proposed procedure allows for the use of a large number of prognostic factors in a given allocation decision. Our method seems adequate for the design of the psychiatric trials used as models. Trial registrations are available at clinicaltrials.gov NCT00466609 and NCT00680602.