Identification of novel common variants associated with chronic pain using conditional false discovery rate analysis with major depressive disorder and assessment of pleiotropic effects of LRFN5

Chronic pain is a complex trait that is moderately heritable and genetically, as well as phenotypically, correlated with major depressive disorder (MDD). Use of the conditional false discovery rate (cFDR) approach, which leverages pleiotropy identified from existing GWAS outputs, has been successful in discovering novel associated variants in related phenotypes. Here, genome-wide association study outputs for both von Korff chronic pain grade and for MDD were used to identify variants meeting a cFDR threshold for each outcome phenotype separately, as well as a conjunctional cFDR (ccFDR) threshold for both phenotypes together. Using a moderately conservative threshold, we identified a total of 11 novel single nucleotide polymorphisms (SNPs), six of which were associated with chronic pain grade and nine of which were associated with MDD. Four SNPs on chromosome 14 were associated with both chronic pain grade and MDD. SNPs associated only with chronic pain grade were located within SLC16A7 on chromosome 12. SNPs associated only with MDD were located either in a gene-dense region on chromosome 1 harbouring LINC01360, LRRIQ3, FPGT and FPGT-TNNI3K, or within/close to LRFN5 on chromosome 14. The SNPs associated with both outcomes were also located within LRFN5. Several of the SNPs on chromosomes 1 and 14 were identified as being associated with expression levels of nearby genes in the brain and central nervous system. Overall, using the cFDR approach, we identified several novel genetic loci associated with chronic pain and we describe likely pleiotropic effects of a recently identified MDD locus on chronic pain

Terapia cognitivo-comportamental com intervenção familiar para crianças e adolescentes com transtorno obsessivo-compulsivo: uma revisão sistemática Cognitive behavioral therapy with family intervention for children and adolescents with obsessive-compulsive disorder: a systematic review

O transtorno obsessivo-compulsivo (TOC) é uma doença mental grave, com graves consequências para a dinâmica familiar. Desta forma, o envolvimento dos pais parece ser determinante na resolução dos sintomas desse transtorno. O objetivo deste estudo foi avaliar a qualidade da evidência para a recomendação de terapia cognitivo-comportamental (TCC) com intervenção familiar para crianças e adolescentes com TOC. A busca sistemática foi realizada nas bases de dados MEDLINE/PubMed, seguida da análise de resumos e artigos na íntegra por dois avaliadores independentes. Posteriormente, foi realizada a análise de evidência através do sistema Grading of Recommendations Assessment, Development and Evaluation (GRADE). O tamanho de efeito da intervenção foi calculado através do d de Cohen. Foram localizados 77 artigos no PubMed e mais 12 artigos após busca cruzada de referências. Destes, sete artigos foram incluídos na revisão, segundo os seguintes critérios: ser estudo de intervenção, envolver apenas crianças e/ou adolescentes e possuir diagnóstico clínico ou estruturado de TOC. A escala Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS) foi utilizada por todos os artigos para a avaliação de desfecho, permitindo avaliar o tamanho de efeito das intervenções não controladas (d = 1,43), que resultou em uma diferença de médias de cerca 13 pontos (IC95% 11,84-14,39; p < 0,001). Por outro lado, uma alta heterogeneidade foi detectada entre os estudos (I² = 67%). A TCC com intervenção familiar parece ter um efeito importante na redução dos sintomas de TOC na infância e adolescência. No entanto, os poucos estudos disponíveis não nos permitem estabelecer um grau de evidência maior do que C para essa recomendação. Novos ensaios clínicos randomizados são necessários para confirmar essa recomendação.<br>Obsessive-compulsive disorder (OCD) is a severe mental disorder with serious consequences to family dynamics. Therefore, parental involvement seems to be a key factor for the successful treatment of this psychiatric disorder. The aim of this study was to evaluate the level of evidence available to allow recommendation of cognitive behavioral therapy (CBT) with family intervention for the treatment of children and adolescents with OCD. The systematic search was performed on MEDLINE/PubMed, followed by analysis of abstracts and full-length articles by two independent evaluators. Subsequently, an analysis of the evidence available was conducted using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The effect size of the intervention was calculated using Cohen’s d. We found 77 articles on PubMed, plus 12 articles via cross-reference search. Of these, seven articles were included in this review, according to the following criteria: intervention study, involving only children and/or adolescents, and a having a structured or clinical diagnosis of OCD. The Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS) was used for outcome evaluation in all articles, thus enabling assessment of the effect size of non-controlled interventions (d = 1.43), resulting in a mean difference of 13.11 points (95%CI 11.84-14.39; p < 0.001). Conversely, a high heterogeneity was detected among the studies (I² = 67%). Family-based CBT seems to have an important effect on the reduction of OCD symptoms in children and adolescents. However, the small number of studies available do not allow us to establish an evidence level higher than C for this recommendation. New randomized clinical trials are needed to confirm this recommendation