Aline Santos Sampaio

Obsessive-compulsive disorder (OCD) affects ∼1% of children and adults and is partly caused by genetic factors. We conducted a genome-wide association study (GWAS) meta-analysis combining 53,660 OCD cases and 2,044,417 controls and identified 30 independent genome-wide significant loci. Gene-based approaches identified 249 potential effector genes for OCD, with 25 of these classified as the most likely causal candidates, including WDR6, DALRD3, CTNND1 and multiple genes in the MHC region. We estimated that ∼11,500 genetic variants explained 90% of OCD genetic heritability. OCD genetic risk was associated with excitatory neurons in the hippocampus and cortex, along with D1- and D2-type dopamine receptor-containing medium spiny neurons. OCD genetic risk was shared with 65 of 112 additional phenotypes, including all of the psychiatric disorders we examined. In particular, OCD shared genetic risk with anxiety, depression, anorexia nervosa, and Tourette syndrome, and was negatively associated with inflammatory bowel diseases, educational attainment, and body mass index.

Background: Health-related quality of life is frequently used as an outcome measure that improves the quality of care. The SF-36 and RAND-36 were derived from the Medical Outcomes Study. Objective The present study aimed to validate the RAND-36 in Brazil, in healthy individuals and patients with liver disease. Methods: Confirmatory factor analysis (CFA) was conducted by using JASP Software. The parameters of the items were estimated using the Robust Diagonally Weighted Least Squares (RDWLS) approach. Comparative fit index (CFI), Goodness-of-fit index (GFI), Tucker-Lewis Index (TLI) and the root mean square error of approximation (RMSEA) were evaluated. Internal consistency was measured using the Composite reliability index. Convergent validity between RAND-36 domains and Work Ability Index (WAI) was conducted. Results: This validation study included 763 individuals, 400 (52.4%) with chronic liver disease. The most prevalent liver diseases were hepatitis C (13.9%), alcoholic liver disease (11.8%), and steatosis (12.1%). The measurement model tested using the CFA obtained the following adjustment indicators: X2 (df): 599.65 (498); CFI: 0.998; GFI: 0.998; TLI: 0.998; RMSEA: 0.016 (90%CI: 0.011-.021). Convergent validity of RAND-36 and total WAI ranged from medium to large correlation. Conclusion: The RAND-36 is effective in measuring the perception of health-related quality of life in individuals with and without chronic liver disease. The results of our study support the developer’s claims for the reliability of the RAND-36 version 1 as a measure of health-related quality of life. The evidence for the construct validity of the RAND-36 was substantial.

Introduction: First-line treatment for obsessive-compulsive disorder (OCD) includes exposure and response prevention behavioral therapy and serotonin reuptake inhibitors, particularly in combination. New and more effective treatments are needed, give that recent studies suggest that glutamatergic neurotransmission contributes to the pathophysiology of the disorder. In these circumstances, ketamine, as a potent N-methyl-D-aspartate receptor antagonist and glutamate modulator, offers alternative possibilities for OCD treatment. Methods: This systematic review aims to investigate the effects of ketamine in OCD, following the Preferred Reporting Items for Systematic Review and Meta-analyses Protocols (PRISMA-P). Searches were carried out using the PubMed/MEDLINE, Embase, and PsycINFO databases. Results: Nine articles were included, of which three were randomized controlled trials, three case reports, two open-label trials, and one a retrospective chart review. Reported data have shown a potential for fast onset of action and good tolerability of ketamine for OCD, even though the principal studies used only single-session racemic ketamine treatments, administered intravenously, and the results have been erratic. In addition, none of the available evidence demonstrates whether racemic ketamine, S-ketamine, or R-ketamine has the best efficacy in controlling OCD symptoms, and only sparse evidence suggests that a combination of ketamine and psychotherapy could benefit patients with OCD. Conclusion: In order to advance clinical practice regarding the use of ketamine in treating OCD, future randomized, double-blind, placebo-controlled trials are required. These trials need to use larger samples to explore ketamine and its enantiomers, with different methods of administration, multiple sessions, and appropriate washout periods.

Obsessive-compulsive disorder (OCD) is a heritable disorder, but no definitive, replicated OCD susceptibility loci have yet been identified by any genome-wide association study (GWAS). Here, we report results from a GWAS in the largest OCD case-control sample (N = 14,140 OCD cases and N = 562,117 controls) to date. We explored the genetic architecture of OCD, including its genetic relationships to other psychiatric and non-psychiatric phenotypes. In the GWAS analysis, we identified one SNP associated with OCD at a genome-wide significant level. Subsequent gene-based analyses identified additional two genes as potentially implicated in OCD pathogenesis. All SNPs combined explained 16% of the heritability of OCD. We show sub-stantial positive genetic correlations between OCD and a range of psychiatric disorders, including anxiety disorders, anorexia nervosa, and major depression. We thus for the first time provide evidence of a genome-wide locus implicated in OCD and strengthen previous literature suggesting a polygenic nature of this disorder.

Learning objective: After participating in this activity, learners should be better able to: • Analyze the effects of ketamine and esketamine on individuals with treatment-resistant depression Introduction: Cognitive impairment is commonly present in individuals with treatment-resistant depression, especially in attention, memory, and executive functions. These deficits are related to symptom severity, remission rates, and functional impairments during and after the acute phase of the disorder. Ketamine, an N-methyl-D-aspartate antagonist previously used as an anesthetic, brings promising antidepressant results. This study systematically reviews the neurocognitive effects of ketamine and esketamine in patients with treatment-resistant major depressive disorder. Methods: Systematic searches were conducted at Embase, PubMed, and PsycINFO using the terms depression, ketamine, and cognition. Title, abstract, and full-text reading were conducted independently by two of the authors (BSM and CSL). Risk of bias, study design, neuropsychological outcomes, and neuroimaging data were recorded. Results: From a total of 997 hits, 14 articles were included. One study reported cognitive impairment after ketamine treatment for processing speed and verbal memory. Five studies reported improvements in processing speed, verbal memory, visual memory, working memory, or cognitive flexibility. The esketamine study suggested no changes to performance. Lower attention, slower processing speed, and higher working memory are reported as predictors of antidepressant response. Brain areas for emotional and reward processing, including the amygdala, insula, and orbitofrontal cortex, show a normalizing tendency after ketamine. Conclusions: Ketamine and esketamine do not seem to exert significant deleterious neurocognitive effects in the short or long term in individuals with treatment-resistant depression. Results suggest neuropsychological functions and brain areas commonly impaired in treatment-resistant depression may especially benefit from subanesthetic ketamine infusions. Key questions that remain unanswered are discussed.

Introdução: A alimentação é um fator de importância para assegurar a existência, o crescimento e o desenvolvimento adequados de uma criança. Objetivos: identificar o perfil socioeconômico das crianças menores de um ano internadas em hospital público no interior do Maranhão e de suas mães; conhecer a alimentação complementar praticada por elas e o histórico de aleitamento materno das mesmas. Método: Pesquisa descritiva, transversal, quantitativa, realizada entre fevereiro e setembro de 2015. Dados coletados através de formulários aplicados às mães, sendo que a amostra compreendeu 174 sujeitos. Resultados: Eram do sexo masculino 62,7% das crianças, 42,5% tinham de 1 a 4 meses, 55,7% foram internadas com problemas respiratórios, suas mães eram donas de casa com idade entre 15 e 35 anos. Os dados mostram que as crianças receberam líquidos, leite artificial e alimentos precocemente, e apenas 20,1% praticaram ao aleitamento materno exclusivo até o sexto mês. Conclusão: As crianças menores de um ano internadas apresentam padrão alimentar inadequado. Portanto, são necessárias ações que promovam a prática da alimentação saudável. Introducción: La fuente de alimentación es un factor importante para asegurar el correcto crecimiento y desarrollo de un niño. Objetivo: Identificar el perfil socioeconómico de los niños menores de un año ingresados en hospital público en interior de Maranhão y de sus madres; conocer la alimentación complementaria practicada por ellas y el histórico de amamantamiento materno. Método: Investigación descriptiva, transversal de naturaleza cuantitativa, realizada entre febrero y septiembre de 2015. Datos recolectados en formularios aplicados a las madres de los niños, siendo la muestra de 174 sujetos. Resultados: Eran del sexo masculino 62,7% de los niños, 42,5% tenían de 1 a 4 meses, 55,7% fueron ingresados con problemas respiratorios, sus madres eran amas de casa con edad entre 15 y 35 años. Los datos muestran que los niños recibieron líquidos, leche artificial y alimentos precozmente, y sólo 20,1% practicaron al amamantamiento materno exclusivo hasta el sexto mes. Conclusión: Los niños menores de un año ingresados presentaron tipo alimentación inadecuado. Por lo tanto, son necesarias acciones que promuevan la práctica de la alimentación saludable. Introduction: Food is an important factor to ensuring the existence, growth and development of a child. Objectives: to identify the socioeconomic profile of children under one year of age hospitalized in a public hospital in the country side of Maranhão and of their mothers; to know the complementary feeding given tby mothers and their history of breastfeeding. Method: Descriptive, cross-sectional, quantitative research conducted between February and September 2015. Data were collected through forms applied to mothers, and the sample comprised 174 individuals. Results: 62.7% of the children were male, 42.5% were 1 to 4 months old, 55.7% were hospitalized with respiratory problems, their mothers were housewives aged between 15 and 35 years. The data showed that children received liquids, artificial milk and food precociously, and only 20.1% had practiced exclusive breastfeeding until the sixth month. Conclusion: The children under one year of age have an inadequate eating pattern. Therefore, actions that promote the practice of healthy feeding are necessary.

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. 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. 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. 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.

Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1465 cases, 5557 ancestry-matched controls and 400 complete trios remained, with a common set of 469 410 autosomal and 9657 X-chromosome single nucleotide polymorphisms (SNPs). Ancestry-stratified case–control association analyses were conducted for three genetically-defined subpopulations and combined in two meta-analyses, with and without the trio-based analysis. In the case–control analysis, the lowest two P-values were located within DLGAP1 (P=2.49 × 10⁻⁶ and P=3.44 × 10⁻⁶), a member of the neuronal postsynaptic density complex. In the trio analysis, rs6131295, near BTBD3, exceeded the genome-wide significance threshold with a P-value=3.84 × 10⁻⁸. However, when trios were meta-analyzed with the case–control samples, the P-value for this variant was 3.62 × 10⁻⁵, losing genome-wide significance. Although no SNPs were identified to be associated with OCD at a genome-wide significant level in the combined trio–case–control sample, a significant enrichment of methylation QTLs (PP=0.001) was observed within the top-ranked SNPs (P<0.01) from the trio–case–control analysis, suggesting these top signals may have a broad role in gene expression in the brain, and possibly in the etiology of OCD.