Longitudinal associations between adolescents' individualised risk for depression and inflammation in a UK cohort study.

Inflammation is associated with poor physical and mental health including major depressive disorder (MDD). Moreover, there is evidence that childhood adversity - a risk factor for MDD - becomes biologically embedded via elevated inflammation. However, the risk of developing MDD arises from multiple sources and yet there has been little investigation of the links between individuals' constellation of MDD risk and subsequent inflammation. We therefore examined associations between individual risk for MDD calculated in early adolescence and levels of inflammation six years later. We use data from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative UK birth cohort of 2,232 children followed to age 18 with 93% retention. Participants' individual risk for developing future MDD was calculated at age 12 using a recently developed prediction model comprising multiple psychosocial factors. Plasma levels of three inflammation biomarkers were measured at age 18: C-reactive protein (CRP), interleukin-6 (IL-6), and a newer biomarker, soluble urokinase plasminogen activator receptor (suPAR), which is thought to reflect the level of systemic chronic inflammation. MDD risk scores calculated at age 12 were positively associated with levels of suPAR (but not CRP or IL-6) at age 18 after adjusting for key covariates (b = 1.70, 95% CI = 0.46 - 2.95, p = 0.007). Adolescents at high risk of MDD (risk scores ≥ 90th centile) had significantly higher mean levels of suPAR six years later than adolescents who had been identified as low risk (risk scores ≤ 10th centile) (b = 0.41, 95% CI = 0.18 - 0.64, p < 0.001). Findings support the notion that childhood psychosocial risk for MDD leads to increased levels of low-grade inflammation. If replicated in studies with repeated assessments of inflammation biomarkers throughout childhood and adolescence, these findings would support targeted interventions to reduce inflammation, as measured by suPAR, for adolescents at high risk of MDD to potentially prevent development of depression and physical health problems related to chronic inflammation.

Identifying Adolescents at Risk for Depression: A Prediction Score Performance in Cohorts Based in 3 Different Continents.

OBJECTIVE: Prediction models have become frequent in the medical literature, but most published studies are conducted in a single setting. Heterogeneity between development and validation samples has been posited as a major obstacle for the generalization of models. We aimed to develop a multivariable prognostic model using sociodemographic variables easily obtainable from adolescents at age 15 to predict a depressive disorder diagnosis at age 18 and to evaluate its generalizability in 2 samples from diverse socioeconomic and cultural settings. METHOD: Data from the 1993 Pelotas Birth Cohort were used to develop the prediction model, and its generalizability was evaluated in 2 representative cohort studies: the Environmental Risk (E-Risk) Longitudinal Twin Study and the Dunedin Multidisciplinary Health and Development Study. RESULTS: At age 15, 2,192 adolescents with no evidence of current or previous depression were included (44.6% male). The apparent C-statistic of the models derived in Pelotas ranged from 0.76 to 0.79, and the model obtained from a penalized logistic regression was selected for subsequent external evaluation. Major discrepancies between the samples were identified, impacting the external prognostic performance of the model (Dunedin and E-Risk C-statistics of 0.63 and 0.59, respectively). The implementation of recommended strategies to account for this heterogeneity among samples improved the model's calibration in both samples. CONCLUSION: An adolescent depression risk score comprising easily obtainable predictors was developed with good prognostic performance in a Brazilian sample. Heterogeneity among settings was not trivial, but strategies to deal with sample diversity were identified as pivotal for providing better risk stratification across samples. Future efforts should focus on developing better methodological approaches for incorporating heterogeneity in prognostic research.

Predicting the risk of depression among adolescents in Nepal using a model developed in Brazil: the IDEA Project.

The burden of adolescent depression is high in low- and middle-income countries (LMICs), yet research into prevention is lacking. Development and validation of models to predict individualized risk of depression among adolescents in LMICs is rare but crucial to ensure appropriate targeting of preventive interventions. We assessed the ability of a model developed in Brazil, a middle-income country, to predict depression in an existing culturally different adolescent cohort from Nepal, a low-income country with a large youth population with high rates of depression. Data were utilized from the longitudinal study of 258 former child soldiers matched with 258 war-affected civilian adolescents in Nepal. Prediction modelling techniques were employed to predict individualized risk of depression at age 18 or older in the Nepali cohort using a penalized logistic regression model. Following a priori exclusions for prior depression and age, 55 child soldiers and 71 war-affected civilians were included in the final analysis. The model was well calibrated, had good overall performance, and achieved good discrimination between depressed and non-depressed individuals with an area under the curve (AUC) of 0.73 (bootstrap-corrected 95% confidence interval 0.62-0.83). The Brazilian model comprising seven matching sociodemographic predictors, was able to stratify individualized risk of depression in a Nepali adolescent cohort. Further testing of the model's performance in larger socio-culturally diverse samples in other geographical regions should be attempted to test the model's wider generalizability.

Predicting the risk of future depression among school-attending adolescents in Nigeria using a model developed in Brazil.

Depression commonly emerges in adolescence and is a major public health issue in low- and middle-income countries where 90% of the world's adolescents live. Thus efforts to prevent depression onset are crucial in countries like Nigeria, where two-thirds of the population are aged under 24. Therefore, we tested the ability of a prediction model developed in Brazil to predict future depression in a Nigerian adolescent sample. Data were obtained from school students aged 14-16 years in Lagos, who were assessed in 2016 and 2019 for depression using a self-completed version of the Mini International Neuropsychiatric Interview for Children and Adolescents. Only the 1,928 students free of depression at baseline were included. Penalized logistic regression was used to predict individualized risk of developing depression at follow-up for each adolescent based on the 7 matching baseline sociodemographic predictors from the Brazilian model. Discrimination between adolescents who did and did not develop depression was better than chance (area under the curve = 0.62 (bootstrap-corrected 95% CI: 0.58-0.66). However, the model was not well-calibrated even after adjustment of the intercept, indicating poorer overall performance compared to the original Brazilian cohort. Updating the model with context-specific factors may improve prediction of depression in this setting.

Translation and cross-cultural adaptation into Brazilian Portuguese of the Mood and Feelings Questionnaire (MFQ) - Long Version.

Introduction Major depressive disorder (MDD) is prevalent among young people, with a high incidence during adolescence. It is, therefore, important to have reliable instruments to capture the construct of depression in this population. The objective of the present work is to describe the process of translation and cultural adaptation of the Mood and Feelings Questionnaire (MFQ) - Long Version, into Brazilian Portuguese. Method We followed the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines for translation and cultural adaptation, including the steps of preparation, forward translation, reconciliation, back-translation, back-translation review, harmonization, cognitive debriefing, review of cognitive debriefing results and finalization, proofreading and final report. Cognitive debriefing was conducted in a sample of adolescent patients and their respective caregivers at mental health clinics affiliated with the Brazilian public health system. Results Results suggest that the items were well understood and that the MFQ seems to be an appropriate instrument for use with Brazilian adolescents and caregivers. Conclusions The Brazilian Portuguese MFQ - Long Version constitutes an adequate tool for the assessment of depression among adolescents. Future studies are required to evaluate psychometric properties of the instrument.

Translation and cross-cultural adaptation into Brazilian Portuguese of the Mood and Feelings Questionnaire (MFQ) - Long Version / Tradução e adaptação transcultural para o português brasileiro do instrumento Mood and Feelings Questionnaire (MFQ) - Versão Longa

Abstract Introduction Major depressive disorder (MDD) is prevalent among young people, with a high incidence during adolescence. It is, therefore, important to have reliable instruments to capture the construct of depression in this population. The objective of the present work is to describe the process of translation and cultural adaptation of the Mood and Feelings Questionnaire (MFQ) - Long Version, into Brazilian Portuguese. Method We followed the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines for translation and cultural adaptation, including the steps of preparation, forward translation, reconciliation, back-translation, back-translation review, harmonization, cognitive debriefing, review of cognitive debriefing results and finalization, proofreading and final report. Cognitive debriefing was conducted in a sample of adolescent patients and their respective caregivers at mental health clinics affiliated with the Brazilian public health system. Results Results suggest that the items were well understood and that the MFQ seems to be an appropriate instrument for use with Brazilian adolescents and caregivers. Conclusions The Brazilian Portuguese MFQ - Long Version constitutes an adequate tool for the assessment of depression among adolescents. Future studies are required to evaluate psychometric properties of the instrument.

Resumo Introdução O transtorno depressivo maior (TDM) é prevalente em jovens, com alta incidência durante a adolescência. Portanto, é importante que instrumentos confiáveis estejam disponíveis para avaliar o construto da depressão nessa população. O objetivo do presente trabalho é descrever o processo de tradução e adaptação cultural do Mood and Feelings Questionnaire (MFQ) - Versão Longa para o português brasileiro. Método Foram utilizadas as diretrizes da International Society for Pharmacoeconomics and Outcomes Research (ISPOR) para tradução e adaptação cultural, incluindo as etapas de preparação, tradução, reconciliação, retrotradução, revisão da retrotradução, harmonização, estudo piloto, revisão dos resultados do estudo piloto, revisão final e relato final. A etapa de estudo piloto foi conduzida em uma amostra de pacientes adolescentes e seus respectivos cuidadores em clínicas de saúde mental afiliadas ao Sistema Único de Saúde. Resultados Os resultados sugeriram que os itens foram bem compreendidos, e que o MFQ parece ser um instrumento apropriado para uso com adolescentes e cuidadores brasileiros. Conclusões A versão traduzida para o português brasileiro do MFQ - Versão Longa constitui um instrumento adequado para a avaliação da depressão em adolescentes. Futuros estudos são necessários para avaliar as propriedades psicométricas da escala.

Attention-Deficit/Hyperactivity Disorder Trajectories From Childhood to Young Adulthood: Evidence From a Birth Cohort Supporting a Late-Onset Syndrome.

IMPORTANCE: The requirement of a childhood onset has always been a key criterion for the diagnosis of attention-deficit/hyperactivity disorder (ADHD) in adults, but recently this requirement has become surrounded by controversy. OBJECTIVE: To investigate whether impaired young adults with ADHD symptoms always have a childhood-onset disorder in a population-based longitudinal study. DESIGN, SETTING, AND PARTICIPANTS: Participants belonged to the 1993 Pelotas Birth Cohort Study, including 5249 individuals born in Pelotas, Brazil, in 1993. They were followed up to 18 to 19 years of age, with 81.3% retention. The data analysis was performed between August 8, 2015, and February 5, 2016. MAIN OUTCOMES AND MEASURES: The ADHD status was first ascertained at 11 years of age using a screening instrument (hyperactivity subscale of the Strength and Difficulties Questionnaire) calibrated for a DSM-IV ADHD diagnosis based on clinical interviews with parents using the Development and Well-Being Assessment. At 18 to 19 years of age, ADHD diagnosis was derived using DSM-5 criteria, except age at onset. We estimated the overlap between these groups assessed at 11 and 18 to 19 years of age and the rates of markers of impairment in these 2 groups compared with those without ADHD. RESULTS: At 11 years of age, childhood ADHD (C-ADHD) was present in 393 individuals (8.9%). At 18 to 19 years of age, 492 individuals (12.2%) fulfilled all DSM-5 criteria for young adult ADHD (YA-ADHD), except age at onset. After comorbidities were excluded, the prevalence of YA-ADHD without comorbidities decreased to 256 individuals (6.3%). Children with C-ADHD had a male preponderance not observed among children without ADHD (251 [63.9%] vs 1930 [47.9%] male, P < .001), whereas the YA-ADHD group had a female preponderance (192 [39.0%] vs 1786 [50.4%] male, P < .001). Both groups had increased levels of impairment in adulthood, as measured by traffic incidents, criminal behavior, incarceration, suicide attempts, and comorbidities. However, only 60 children (17.2%) with ADHD continued to have ADHD as young adults, and only 60 young adults (12.6%) with ADHD had the disorder in childhood. CONCLUSIONS AND RELEVANCE: The findings of this study do not support the assumption that adulthood ADHD is necessarily a continuation of childhood ADHD. Rather, they suggest the existence of 2 syndromes that have distinct developmental trajectories.

Gene-Environment Interaction in Youth Depression: Replication of the 5-HTTLPR Moderation in a Diverse Setting.

OBJECTIVE: Replication of scientific findings is a major challenge in biomedical research. In psychiatry, the identification of measured gene-environment interactions (G×E) has promoted a heated debate over the past decade, with controversial results about its influence on disorders such as major depression. The authors sought to replicate a 2003 study on G×E in youth depression in a large birth cohort from a diverse setting. METHOD: Using data from the 1993 Pelotas Birth Cohort Study, and adopting a design as similar as possible to that of the original study, the authors tested whether the relationship between childhood maltreatment and a subsequent depressive episode diagnosis was moderated by 5-HTTLPR genotype. Of 5,249 individuals assessed at birth and followed up to age 18, data on the evaluation for depressive episodes in early adulthood, on childhood maltreatment, and on genotype were available for 3,558 participants, of whom 2,392 remained after conservative screening for previous depressive symptoms. Associations were investigated with logistic regression analyses and controlling for potential confounders. RESULTS: The results replicated important findings of the original study, this time in a sample of young adults from a middle-income country: there was a differential dose-response relationship between childhood maltreatment and major depression according to 5-HTTLPR genotype. CONCLUSIONS: After following a research strategy as comparable as possible to that of the original study, the results corroborated the existence of a measured G×E, now in a large sample from a different sociocultural context. These findings provide further evidence that a genetic variant in the 5-HTTLPR moderates the link between childhood maltreatment and youth depression.

Provision of mental healthcare for children and adolescents: a worldwide view.

PURPOSE OF REVIEW: There has been increased attention towards the burden imposed by mental disorders on children and adolescents. The present overview explores the current state of child and adolescent mental healthcare provision around the globe. RECENT FINDINGS: Current research indicates a concerning gap in the provision of care for the child and adolescent population. The disparities between need, demand and access to youth mental healthcare are likely to be even greater in low and- middle-income countries (LAMIC), where the proportion of children and adolescents in the population is higher. The scarcity of available resources for youth mental healthcare, especially in LAMIC, represents a major obstacle to decreasing the impact of mental disorders across the lifespan. SUMMARY: Our review highlights the discrepancy between demands and availability of mental healthcare for youth populations throughout the world. We describe some of the potential contributors to the current state of youth mental healthcare, such as problematic access to services, implementation deficiencies and inadequacy of policies. Recent innovative strategies to reduce these barriers are also presented.

Mood disorders in childhood and adolescence.

The identification and treatment of mood disorders in children and adolescents has grown over the last decades. Major depression is one of the most common and debilitating disorders worldwide, imposing a massive burden to the youth population. Bipolar disorder is being increasingly recognized as having its roots early in life, and its presentation during childhood and adolescence has been submitted to extensive research. This review aims to highlight clinical aspects of the current knowledge on mood disorders in the pediatric population, presenting updated information on epidemiology, diagnostic procedures, and management strategies. Limitations of available evidence and future directions of research in the field are also discussed.

Mood disorders in childhood and adolescence

The identification and treatment of mood disorders in children and adolescents has grown over the last decades. Major depression is one of the most common and debilitating disorders worldwide, imposing a massive burden to the youth population. Bipolar disorder is being increasingly recognized as having its roots early in life, and its presentation during childhood and adolescence has been submitted to extensive research. This review aims to highlight clinical aspects of the current knowledge on mood disorders in the pediatric population, presenting updated information on epidemiology, diagnostic procedures, and management strategies. Limitations of available evidence and future directions of research in the field are also discussed.

Age of Sexual Initiation, Psychiatric Symptoms, and Sexual Risk Behavior among Ecstasy and LSD Users in Porto Alegre, Brazil: A Preliminary Analysis.

Ecstasy and LSD use is widespread in large Brazilian cities, but there is limited information on their use among young, middle-class, club goers in Brazil. We conducted standardized face-to-face interviews with 200 male and female ecstasy and/or LSD users, focusing on drug use and sexual history, current risk behaviors, and psychiatric symptomatology. Participants with early sexual debut (before 14) were more likely to report lifetime use of marijuana and powder and crack cocaine than those with later sexual initiation. Early sexual debut was associated with past year sexual risk behaviors, including having sex while high (Prevalence Ratio (PR)=1.3), having two or more sex partners (PR=1.3), as well as history of sexual abuse (PR=13.6). Depression and anxiety scores were similar by age of sexual initiation. The implications of these findings are discussed.