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BACKGROUND. The Identifying Depression Early in Adolescence Risk Score (IDEA-RS) has been externally assessed in samples from four continents, but North America is lacking. Our aim here was to evaluate the performance of the IDEA-RS in predicting future onset of Major Depressive Disorder (MDD) among adolescents from the United States of America. METHODS. We applied the intercept and weights of the original IDEA-RS model developed in Brazil to the Great Smoky Mountains Study (GSMS) sample to generate individual probabilities for each participant at age 15 (N = 1029). We then evaluated the performance of such predictions against the diagnosis of MDD at age 19 using simple, case-mix corrected and refitted models. Furthermore, we compared how prioritizing the information provided by parents or by adolescents affected performance. RESULTS. The IDEA-RS exhibited a C-statistic of 0.63 (95% CI 0.53–0.74) to predict MDD in the GSMS when applying uncorrected weights. Case-mix corrected and refitted models enhanced performance to 0.69 and 0.67, respectively. No significant difference was found in performance by prioritizing the reports of adolescents or their parents. CONCLUSION. The IDEA-RS was able to parse out adolescents at risk for a later onset of depression in the GSMS cohort with above chance discrimination. The IDEA-RS has now showed above-chance performance in five continents.

Background Trajectories of attention-deficit hyperactivity disorder (ADHD) traits spanning early childhood to mid-life have not been described in general populations across different geographical contexts. Population trajectories are crucial to better understanding typical developmental patterns. Methods We combined repeated assessments of ADHD traits from five population-based cohorts, spanning ages 3 to 45 years. We used two measures: (i) the Strengths and Difficulties Questionnaire (SDQ) hyperactive-inattentive subscale (175 831 observations, 29 519 individuals); and (ii) scores from DSM-referenced scales (118 144 observations, 28 685 individuals). Multilevel linear spline models allowed for non-linear change over time and differences between cohorts and raters (parent/teacher/self). Results Patterns of age-related change differed by measure, cohort and country: overall, SDQ scores decreased with age, most rapidly declining before age 8 years (-0.157, 95% CI: -0.170, -0.144 per year). The pattern was generally consistent using DSM scores, although with greater between-cohort variation. DSM scores decreased most rapidly between ages 14 and 17 years (-1.32%, 95% CI: -1.471, -1.170 per year). Average scores were consistently lower for females than males (SDQ: -0.818, 95% CI: -0.856, -0.780; DSM: -4.934%, 95% CI: -5.378, -4.489). This sex difference decreased over age for both measures, due to an overall steeper decrease for males. Conclusions ADHD trait scores declined from childhood to mid-life, with marked variation between cohorts. Our results highlight the importance of taking a developmental perspective when considering typical population traits. When interpreting changes in clinical cohorts, it is important to consider the pattern of expected change within the general population, which is influenced by cultural context and measurement.

Background Lesbian, Gay, Bisexual, Transgender, Queer, and Asexual (LGBTQA+) youth have a greater chance of experiencing stressful life events when compared to cisgender heterosexual peers, which can lead to mental health problems. We aimed to estimate the prevalence of mental disorders among LGBTQA+ youths from two large cities in Brazil. Methods Participants were 13–22 years old youths from the 3rd wave of the Brazilian High-Risk Cohort for Psychiatric Disorders (n = 1475). Mental disorders were assessed using the Development and Well-Being Behavior Assessment. Sexual orientation and gender identity were assessed using a self-report confidential questionnaire. Data were analyzed through logistic regressions (adjusting for sociodemographic) using sampling weights to account for attrition and our oversampling high-risk design. Results 15.18% of the sample described themselves as LGBTQA+. The LGBTQA+ group presented higher rates of anxiety disorders (30.14% vs. 13.37%; OR = 3.37; 95%CI:2.51–4.50), depressive disorders (27.75% vs. 15.34%; OR = 2.17; 95%CI:1.60–2.93) and post-traumatic stress disorder (4.98% vs. 2.25%; OR = 4.20; 95%CI:2.24–7.82), if compared with the cisgender heterosexual group. No difference was found for conduct disorders (2.97% vs. 5.21%; OR = 0.82; 95%CI:0.35–1.65) or attention deficit hyperactivity disorder (5.92% vs. 3.28%; OR = 1.56; 95%CI:0.83–2.79). Limitations Although recruitment was performed at 57 schools in the two cities, sampling was non-probabilistic and included only urban areas, which might bias prevalence estimates and group comparisons. Conclusions Our results elucidate the mental health disparities between LGBTQA+ people and cisgender heterosexuals in Brazil. It highlights the need to promote the inclusion of this population in policy formulation and support actions to mitigate the suffering related to sexual orientation and gender identity.

The world's population is increasingly urban, with most children and young people growing up and living in cities. Evidence suggests that urbanicity is linked to an increased risk for the development of mental health disorders. Rather than an accumulation of risk factors, urbanization is a complex process that profoundly structures living conditions. In this sense, it is timely to discuss what are the social and structural determinants of mental health of children and young people in such settings.Three domains of determinants of mental health were selected for discussion: economics and living conditions, crime and violence, and urban layouts. For each, we debated realities faced by urban children and young people, providing an overview of recent evidence on implications for mental disorders and well being. We also discuss the potential impacts of the covid-19 pandemic on each domain, as well as recommendations for future action.Structural factors are of major relevance for the mental health of children and young people living in cities. The agenda of mental health promotion and prevention must include whole-of-society interventions aimed at improving living conditions, including economic and social capital, violence prevention and urbanistic planning.

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 two 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 two 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.

Study Objectives Major depressive disorder (MDD) in adolescence is associated with irregularities in circadian rhythms and sleep. The characterization of such impairment may be critical to design effective interventions to prevent development of depression among adolescents. This study aimed to examine self-reported and actimetry-based circadian rhythms and sleep–wake behavior associated with current MDD and high risk (HR) for MDD among adolescents. Methods Ninety-six adolescents who took part in the IDEA-RiSCo study were recruited using an empirically developed depression-risk stratification method: 26 classified as low risk (LR), 31 as HR, and 39 as a current depressive episode (MDD). We collected self-report data on insomnia, chronotype, sleep schedule, sleep hygiene as well as objective data on sleep, rest-activity, and light exposure rhythms using actimetry for 10 days. Results Adolescents with MDD exhibited more severe insomnia, shorter sleep duration, higher social jetlag (SJL), lower relative amplitude (RA) of activity, and higher exposure to artificial light at night (ALAN) compared with the other groups. They also presented poorer sleep hygiene compared with the LR group. The HR group also showed higher insomnia, lower RA, higher exposure to ALAN, and higher SJL compared with the LR group. Conclusions HR adolescents shared sleep and rhythm alterations with the MDD group, which may constitute early signs of depression, suggesting that preventive strategies targeting sleep should be examined in future studies. Furthermore, we highlight that actimetry-based parameters of motor activity (particularly RA) and light exposure are promising constructs to be explored as tools for assessment of depression in adolescence.

Attention-Deficit Hyperactivity Disorder (ADHD) is a prevalent neuropsychiatric disorder associated with significant impairment and distress throughout the lifespan. Recent investigations have shed light on different aspects regarding the trajectory of ADHD, including reports on risk factors in childhood, that are associated with remission or persistence in adulthood. Despite significant advances in our understanding of the pathophysiology of the disorder, the diagnosis of ADHD remains strictly clinical and is based on behavioral symptoms of inattention, impulsivity, and hyperactivity. In this chapter we review the diagnostic process of ADHD, discuss the clinical presentation of the disorder across the lifespan, and examine patterns of comorbidity and longitudinal predictor of outcomes.

Summary Background Better understanding of the heterogeneity of treatment responses could help to improve care for adolescents with depression. We analysed data from a clinical trial to assess whether specific symptom clusters responded differently to various treatments. Methods For this secondary analysis, we used data from the Treatment for Adolescents with Depression Study (TADS), in which 439 US adolescents aged 12–17 with a DSM-IV diagnosis of major depressive disorder and a minimum score of 45 on the Children's Depression Rating Scale-Revised (CDRS-R) were randomly assigned (1:1:1:1) to treatment with fluoxetine, cognitive behavioural therapy (CBT), fluoxetine plus CBT, or pill placebo. Our analysis focuses on the acute phase of the trial (ie, the first 12 weeks). Groups of co-occurring symptoms were established by clustering scores for each CDRS-R item at baseline with Ward's method, with Euclidean distances for hierarchical agglomerative clustering. We then used a linear mixed-effects model to investigate the relationship between symptom clusters and treatment efficacy, with the sum of symptom scores within each cluster as the dependent measure. As fixed effects, we entered cluster, time, and treatment assignment, with all two-way and three-way interactions, into the model. The random effect providing better fit was established to be a by-subject random slope for cluster based on improvement in the Schwarz-Bayesian information criterion. Outcomes We identified two symptom clusters: cluster 1 comprised depressed mood, difficulty having fun, irritability, social withdrawal, sleep disturbance, impaired schoolwork, excessive fatigue, and low self-esteem, and cluster 2 comprised increased appetite, physical complaints, excessive weeping, decreased appetite, excessive guilt, morbid ideation, and suicidal ideation. For cluster 1 symptoms, CDRS-R scores were reduced by 5·8 points (95% CI 2·8–8·9) in adolescents treated with fluoxetine plus CBT, and by 4·1 points (1·1–7·1) in those treated with fluoxetine, compared with those given placebo. For cluster 2 symptoms, no significant differences in improvements in CDRS-R scores were detected between the active treatment and placebo groups. Interpretation Response to fluoxetine and CBT among adolescents with depression is heterogeneous. Clinicians should consider clinical profile when selecting therapeutic modality. The contrast in response patterns between symptom clusters could provide opportunities to improve treatment efficacy by gearing the development of new therapies towards the resolution of specific symptoms. Funding Conselho Nacional de Desenvolvimento Cientifico e Tecnologico.

Very preterm/very low birth weight (VP/VLBW) newborns can have lifelong morbidities, as attention-deficit/hyperactivity disorder (ADHD). Clinicians have no markers to discriminate which among those individuals will develop later ADHD, based only on the clinical presentation at birth. Our aim was to develop an individualized risk calculator for ADHD in VP/VLBW newborns.This retrospective prognostic study included a consecutive sample of all VP/VLBW children (gestational age32 weeks and/or birth weight1.5 kg) born between 2010 and 2012 from a clinical cohort in a Brazilian tertiary care hospital. Children were clinically assessed at 6 years of age for ADHD using the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS). The least absolute shrinkage and selection operator (LASSO) method was used for model-building.Ninety-six VP/VLBW children were assessed at 6 years of age (92% follow-up), of whom 32 (33%) were diagnosed with ADHD. The area under the ROC curve (AUC) for ADHD prediction based on seven parameters (late-onset sepsis confirmed by blood culture, necrotizing enterocolitis, neonatal seizures, periventricular leukomalacia, respiratory distress syndrome, length of hospital stay, and number of maternal ADHD symptoms) was .875 (CI, 0.800-0.942, p .001; AUC corrected for optimism with bootstrapping: .806), a performance that is comparable to other medical risk calculators. Compared to approaches that would offer early intervention to all, or intervention to none, the risk calculator will be more useful in selecting VP/VLBW newborns, with statistically significant net benefits at cost:benefits of around 1:2 to around 10:6 (range of ADHD risk thresholds of 32%-62%, respectively). It also showed specificity for ADHD compared to other prevalent child psychopathologies.The risk calculator showed good performance for early identification of VP/VLBW newborns at high risk of future ADHD diagnosis. External validity in population-based samples is needed to extend clinical usefulness.

To explore associations between self-reported weekly physical activity and depressive symptomatology among adolescents in a school-based sample from Brazil.We surveyed 7,405 adolescents aged 14 to 16 years in 101 public schools in Porto Alegre, Brazil. We assessed physical activity using an adapted version of the Patient-Centered Assessment and Counseling for Exercise Plus Nutrition - Adolescent Physical Activity Measure (PACE+), and depressive symptoms using the Brazilian Portuguese version of the Patient Health Questionnaire - Adolescent Version. We compared the depressive symptom scores among adolescents with varying levels of physical activity.Of the overall sample, 84.4% exercised less than the recommended frequency of 60 minutes/day, at least 5 days/week, of moderate to intense physical activity (PACE+ score ≥ 5). Adolescents whose physical activity levels fell below that threshold had higher median depression scores (8 [IQR = 10] vs. 7 [IQR = 9], W = 4060461, p0.001). A similar pattern was observed for depression scores in those with PACE+1 (median of 10 [IQR = 11]) and ≥ 1 (7 [IQR = 9], W = 7457608, p0.001).In this large sample of Brazilian adolescents, those who exercised less frequently and vigorously than their peers reported more depressive symptoms.

In this issue of the JAACAP, Kuntsi et al.7 reports from the Swedish national registers to analyze the outcomes of almost 300,000 individuals who were relatively young or relatively old in class (ie, born in the 2 months before and after the national cut-off for school entrance in Sweden). Four events were measured between 15 and 23 years of age: low educational achievement, a conviction of any crime, substance use disorder, and depression. As predicted, young relative age was a risk factor for ADHD (with an odds ratio of 1.7), which in turn was a risk factor for all 4 outcomes considered (with odds ratios of 3.5-5.2). The novelty of their analyses, however, was to evaluate the additive effects of relative young age beyond ADHD on negative long-term outcomes. For the first time, Kuntsi et al.7 demonstrated that children with ADHD who are the youngest in their class are at increased risk for lower educational achievement and receiving a diagnosis of substance use disorder when compared to children with ADHD who are the oldest in their class.

BackgroundADHD diagnosis requires the presence of symptoms before the age of twelve. In clinical assessment of adults, the most frequent strategy to check this criterion is investigating self-report recall of symptoms, despite little evidence on the validity of this approach. We aim to evaluate the recall accuracy and factors associated with its reliability in a large population-based sample of adults.MethodsIndividuals from the 1993 Pelotas Birth Cohort were followed-up from childhood to adulthood. At the age of 22, 3810 individuals were assessed through structured interviews by trained psychologists regarding mental health outcomes, including ADHD diagnosis and ADHD symptoms in childhood. The retrospective recall was compared with available information on ADHD childhood symptoms at the age of eleven. We also assessed factors related to recall accuracy through multiple regression analyses.ResultsSelf-reported recall of childhood symptoms at 22 years of age had an accuracy of only 55.4%, with sensitivity of 32.8% and positive predictive value of 40.7%. Current inattention symptoms were associated with lower risk and social phobia with higher risk for false-positive endorsement, while higher levels of schooling correlated with lower risk and male gender with higher risk for false-negative endorsement.ConclusionsClinicians treating male patients with social phobia and ADHD symptoms should assess even more carefully retrospective recall of ADHD childhood symptoms. Moreover, characteristics associated with recall improvement do not impact accuracy robustly. In this context, the recall of childhood ADHD symptoms seems an unreliable method to characterize the neurodevelopmental trajectory in adults with currently-impairing ADHD symptomatology.

Objective: Recent studies suggest attention-deficit/hyperactivity disorder (ADHD) may emerge post-childhood. We integrate qualitative methods to systematically characterize contextual factors that may (a) delay identification of ADHD in childhood and (b) inform why ADHD symptoms emerge post-childhood. Method: Suspected late-onset ADHD cases from the local normative comparison group of the Multimodal Treatment Study of ADHD completed a qualitative interview (14 young adults and 7 caregivers). Interviews were qualitatively analyzed. Results: We identified five themes. Three themes may attenuate or delay identification of childhood ADHD: external factors (e.g., supportive adults), internal factors (e.g., strong intellectual functioning), and other factors (e.g., dismissive attitudes toward ADHD). Two themes may accompany an increase in ADHD symptoms post-childhood: external factors (e.g., increased external demands) and internal factors (e.g., perceived stress). Conclusion: Clinicians should probe these factors in suspected late-onset cases to address (a) whether, how, and to what extent ADHD was attenuated in childhood and (b) why symptoms emerge post-childhood.

We aimed to investigate the influence of media portrayals of suicide on adolescents' mood, focusing on the case of 13 Reasons Why, a webseries that raised concerns for approaching suicide explicitly for an audience mostly composed of adolescents. There is already evidence of an increase in suicide-related Internet searches shortly following its release. Our study included 7004 individuals aged 12-18 years. Participants were recruited through posts on 13 Reasons Why-themed social media groups. Volunteers filled an online questionnaire made available throughout May 2017 (54-71 days after the show was released). The questionnaire collected data on sociodemographic characteristics, mood (sadness and lack of motivation) in the month previous to watching the series, and prevalence of self-harm, suicidal ideation, or suicide attempts. Changes in mood were considered the main outcome; the variable was derived from a question asking about feelings of sadness and lack of motivation after watching the show. Overall, 23.7% reported worsening in mood after watching 13 Reasons Why. This rate was higher among individuals who, before watching the series, experienced more frequent and intense feelings of sadness and lack of motivation (OR 2.73 for frequent or daily feelings; OR 3.61 for intense feelings) or reported suicidal ideation/self-harm/suicide attempt (OR 1.38), even after controlling for sex and age. In times of easy access to digital content and binge-watching, the way mental health issues are portrayed in fiction needs to be carefully debated and thought out.

There is a high comorbidity between attention-deficit/hyperactivity disorder (ADHD) and asthma, and inflammation has been proposed as a potential pathophysiological mechanism behind this association. Most studies conducted so far have used a cross-sectional design, and none has evaluated the prevalence of asthma symptoms in patients with ADHD followed from childhood to adulthood. We relied on data from the 1993 Pelotas birth cohort to evaluate the association between ADHD and asthma in patients with distinct patterns of incidence, persistence and remission, and to explore the potential role of inflammatory markers in the comorbidity. We analyzed data from 3281 individuals from the 1993 Pelotas birth cohort collected at birth (1993), 11 years (2004), 18 years (2011), and 22 years (2015). Subjects were first classified according to their ADHD and asthma status as early-onset (EO) persistent (positive screening for ADHD at 11 years and diagnosis of ADHD according to DSM-5, except criterion E, at either 18 or 22 years), EO-remittent (positive screening for ADHD at 11 years only), late-onset (diagnosis of ADHD according to DSM-5, except criterion E, at 18 or 22 years only), or healthy subjects (negative for both conditions in all evaluation). After controlling for confounders, significant associations were observed between EO-remittent ADHD and EO-remittent asthma (OR 1.68, 95% CI 1.11–2.55), EO-persistent ADHD and EO-persistent asthma (OR 4.33, 95% CI 1.65–11.34), and between late-onset ADHD and late-onset asthma (OR 1.86, 95% CI 1.28–2.70), suggesting a state-dependent association. Serum interleukin-6 (IL-6) and C-reactive protein (CRP) were measured at the 18- and 22-year evaluations and compared between subjects positive for ADHD, asthma, and subjects with both or none conditions, regardless of the previously defined trajectories. Subjects with comorbid ADHD and asthma presented higher levels of IL-6 at the 18- and 22-year evaluations when compared to subjects negative for both conditions. Our results demonstrate a state-dependent association between ADHD and asthma despite underlying trajectories. Higher levels of serum IL-6 in patients with both conditions suggest that a pro-inflammatory environment might have a role in the pathophysiological mechanisms underlying the comorbidity.

BackgroundPopulation studies have suggested that most adults with attention-deficit hyperactivity disorder (ADHD) did not have the disorder in childhood, challenging the neurodevelopmental conceptualisation of ADHD. Arbitrary definitions of age at onset and lack of defined trajectories were accounted for the findings.AimsThe objective of this study was to assess the proportion of individuals presenting with either a neurodevelopmental trajectory or late-onset disorder, and to assess risk factors associated with them.MethodData of 4676 individuals from the 1993 Pelotas birth cohort at 11, 15, 18 and 22 years of age were used. Polythetic and latent class mixed model analyses were performed to define ADHD trajectories from childhood to adulthood, and characterise the neurodevelopmental or late-onset courses. Regression models were applied to assess factors associated with different trajectories.ResultsClassical polythetic analyses showed that 67% of those with ADHD at 22 years of age had a neurodevelopmental course of the disorder. Latent class mixed model analysis indicated that 78% of adults with ADHD had a trajectory of persistent symptoms, more common in males. The remaining adults with ADHD had an ascending symptom trajectory that occurred after puberty, with late-onset ADHD associated with female gender and higher IQ.ConclusionsBoth polythetic and latent trajectories analyses provided empirical evidence supporting that the large majority of adults with ADHD had a neurodevelopmental disorder.

Objective: Significant anxiety often occurs in the presence of ADHD symptoms; however, the reasons are not well understood. We aimed to establish whether the relations between ADHD symptons and anxiety are bidirectional or unidirectional. Method: Weexamined the developmental relations between ADHD and anxiety symptoms across adolescence (ages 13, 15, and 17) in a community-ascertained, normative longitudinal sample of 1,483 youth (52% male). We used an autoregressive latent trajectory model with structured residuals (ALT-SR) to examine within-person developmental relations between ADHD and anxiety symptoms to determine whether it is ADHD symptoms that lead to anxiety symptoms and/or the reverse. Results: Results suggested that there are reciprocal within-person developmental relations between ADHD and anxiety symptoms. Conclusions: Our findings support the recommendation that targeting ADHD symptoms can be fruitful for addressing anxiety symptoms; however, they suggest that targeting anxiety symptoms may also benefit ADHD symptoms. Results also underline the importance of careful assessment for underlying ADHD symptoms among adolescents presenting with anxiety.

Attention-deficit/hyperactivity disorder (ADHD) is a common and impairing disorder affecting children, adolescents, and adults. Several treatment strategies are available that can successfully ameliorate symptoms, ranging from pharmacological to dietary interventions. Due to the increasing range of available options, an informed selection or prioritization of treatments is becoming harder for clinicians. This review aims to provide an evidence-based appraisal of the literature on ADHD treatment, supplemented by expert opinion on plausibility. We outline proposed mechanisms of action of established pharmacologic and non-pharmacologic treatments, and we review targets of novel treatments. The most relevant evidence supporting efficacy and safety of each treatment strategy is discussed. We review the individualized features of the patient that should guide the selection of treatments in a shared decision-making continuum. We provide guidance for optimizing initiation of treatment and follow-up of patients in clinical settings.

Selective serotonin reuptake inhibitors (SSRI) have been claimed to negatively affect the thyroid function, albeit the evidence is controversial. We searched for studies that measured parameters of thyroid function (TSH, T4, Free T4, or T3) before and after a course of SSRI treatment in euthyroid patients with major depressive disorder. Electronic searches were conducted on MEDLINE, Embase and Web of Science databases from inception through April 4th, 2018. We performed random-effects meta-analyses to estimate the effect of SSRIs on each hormone. A total 1791 records were identified in the electronic search, and 14 observational clinical studies were included in the analyses. All studies had at least moderate risk of bias and were considered of low quality. A course of SSRI treatment was associated with a decrease in T4 of –6.58 nmol/L (95% Confidence Interval [CI], –12.17 to –.99, p = .005, I2=97%; Cohen's d = .50), a decrease in Free T4 of –.91 pmol/L (95% CI, –1.65 to –.16, p = .017, I2=96%; Cohen's d = .66), and a decrease in T3 of –.10 nmol/L (95% CI, –.18 to –.03, p = .007, I2=96%; Cohen's d = .45), and no effect on TSH (0.06 microIU/L, 95% CI, –.05 to .17, p = .285, I2=98%; Cohen's d = .17). We did not detect publication bias in any of the four meta-analyses. We conclude that there is preliminary evidence that SSRIs slightly decrease thyroid function, but quality of evidence is low. Clinical magnitude of such effect is yet unclear.

Aim Few personalised medicine investigations have been conducted for mental health. We aimed to generate and validate a risk tool that predicts adult attention-deficit/hyperactivity disorder (ADHD). Methods Using logistic regression models, we generated a risk tool in a representative population cohort (ALSPAC – UK, 5113 participants, followed from birth to age 17) using childhood clinical and sociodemographic data with internal validation. Predictors included sex, socioeconomic status, single-parent family, ADHD symptoms, comorbid disruptive disorders, childhood maltreatment, ADHD symptoms, depressive symptoms, mother's depression and intelligence quotient. The outcome was defined as a categorical diagnosis of ADHD in young adulthood without requiring age at onset criteria. We also tested Machine Learning approaches for developing the risk models: Random Forest, Stochastic Gradient Boosting and Artificial Neural Network. The risk tool was externally validated in the E-Risk cohort (UK, 2040 participants, birth to age 18), the 1993 Pelotas Birth Cohort (Brazil, 3911 participants, birth to age 18) and the MTA clinical sample (USA, 476 children with ADHD and 241 controls followed for 16 years from a minimum of 8 and a maximum of 26 years old). Results The overall prevalence of adult ADHD ranged from 8.1 to 12% in the population-based samples, and was 28.6% in the clinical sample. The internal performance of the model in the generating sample was good, with an area under the curve (AUC) for predicting adult ADHD of 0.82 (95% confidence interval (CI) 0.79–0.83). Calibration plots showed good agreement between predicted and observed event frequencies from 0 to 60% probability. In the UK birth cohort test sample, the AUC was 0.75 (95% CI 0.71–0.78). In the Brazilian birth cohort test sample, the AUC was significantly lower –0.57 (95% CI 0.54–0.60). In the clinical trial test sample, the AUC was 0.76 (95% CI 0.73–0.80). The risk model did not predict adult anxiety or major depressive disorder. Machine Learning approaches did not outperform logistic regression models. An open-source and free risk calculator was generated for clinical use and is available online at https://ufrgs.br/prodah/adhd-calculator/. Conclusions The risk tool based on childhood characteristics specifically predicts adult ADHD in European and North-American population-based and clinical samples with comparable discrimination to commonly used clinical tools in internal medicine and higher than most previous attempts for mental and neurological disorders. However, its use in middle-income settings requires caution.

To investigate the effect of relatively younger age on attention-deficit/hyperactivity disorder (ADHD) symptoms and diagnosis through three population-based cohorts and a meta-analysis.This study included participants of three community-based cohorts in Brazil: 1993 Pelotas Cohort (N = 5,249), 2004 Pelotas Cohort (N = 4,231), and Brazilian High-Risk Study for Psychiatric Disorders (HRC study) (N = 2,511). We analyzed the effect of relatively younger age on ADHD symptoms and diagnosis. For the meta-analysis, we searched MEDLINE, PsycINFO, and Web of Science from inception through December 25, 2018. We selected studies that reported measures of association between relative immaturity and an ADHD diagnosis. We followed the Meta-analysis Of Observational Studies in Epidemiology guidelines. The protocol for meta-analysis is available on PROSPERO (CRD42018099966).In the meta-analysis, we identified 1,799 potentially eligible records, from which 25 studies including 8,076,570 subjects (164,049 ADHD cases) were analyzed with their effect estimates. The summarized relative risk of an ADHD diagnosis was 1.34 (95% CI, 1.26-1.43, p .001) for children born in the first 4 months of the school year (relatively younger). Heterogeneity was high (IChildren and adolescents who are relatively younger compared with their classmates have a higher risk of receiving an ADHD diagnosis. Clinicians should consider the developmental level of young children when evaluating ADHD symptoms.

Attention-deficit/hyperactivity disorder (ADHD) is traditionally conceptualized as a neurodevelopmental disorder that continues into adulthood in up to half of diagnosed cases. In light of current evidence, factors associated with the course of the disorder remain unknown. We performed a systematic review of the literature searching for risk markers from childhood that predicted the persistence of ADHD into adulthood. We reviewed 26,168 abstracts and selected 72 for full-text review. We identified data from 16 studies, comprising 6 population-based retrospective samples and 10 clinical follow-ups. We performed meta-analyses of factors evaluated by at least three studies. Severity of ADHD (OR 2.33, 95 % CI = 1.6–3.39, p < 0.001), treatment for ADHD (OR 2.09, 95 % CI = 1.04–4.18, p = 0.037), comorbid conduct disorder (OR 1.85, 95 % CI = 1.06–3.24, p = 0.030), and comorbid major depressive disorder (OR 1.8, 95 % CI = 1.1–2.95, p = 0.019) emerged as predictors already presented in childhood for ADHD persistence into adulthood. Further, we suggest that cohort studies should be designed to clarify such an important question for research and clinical practice.

The traditional definition of Attention-Deficit/Hyperactivity Disorder (ADHD), assuming onset in childhood, has been challenged by evidence from four recent birth-cohort studies that reported most adults with ADHD lacked a childhood categorical ADHD diagnosis. Late onset of symptoms was evaluated in the long-term follow-up of the Multimodal Treatment study of ADHD (MTA). In most cases, other factors were present that discounted the late onset of ADHD symptoms and excluded the diagnosis of ADHD. We offer two theoretical frameworks for understanding the ADHD trajectory throughout the life cycle: (1) the complex phenotype model, and (2) the restricted phenotype model. We conclude that (a) late onset (after age 12) is a valid trajectory for ADHD symptoms, (b) the percentage of these cases with onset after adolescence is yet uncertain, and (c) the percentage meeting exclusion criteria for diagnosis of ADHD is influenced by the rigor of the methodology used to obtain evidence and whether or not DSM exclusionary criteria are applied.

Adolescents and young adults without childhood attention deficit hyperactivity disorder (ADHD) often present to clinics seeking stimulant medication for late-onset ADHD symptoms. Recent birth-cohort studies support the notion of late-onset ADHD, but these investigations are limited by relying on screening instruments to assess ADHD, not considering alternative causes of symptoms, or failing to obtain complete psychiatric histories. The authors address these limitations by examining psychiatric assessments administered longitudinally to the local normative comparison group of the Multimodal Treatment Study of ADHD.Individuals without childhood ADHD (N=239) were administered eight assessments from comparison baseline (mean age=9.89 years) to young adulthood (mean age=24.40 years). Diagnostic procedures utilized parent, teacher, and self-reports of ADHD symptoms, impairment, substance use, and other mental disorders, with consideration of symptom context and timing.Approximately 95% of individuals who initially screened positive on symptom checklists were excluded from late-onset ADHD diagnosis. Among individuals with impairing late-onset ADHD symptoms, the most common reason for diagnostic exclusion was symptoms or impairment occurring exclusively in the context of heavy substance use. Most late-onset cases displayed onset in adolescence and an adolescence-limited presentation. There was no evidence for adult-onset ADHD independent of a complex psychiatric history.Individuals seeking treatment for late-onset ADHD may be valid cases; however, more commonly, symptoms represent nonimpairing cognitive fluctuations, a comorbid disorder, or the cognitive effects of substance use. False positive late-onset ADHD cases are common without careful assessment. Clinicians should carefully assess impairment, psychiatric history, and substance use before treating potential late-onset cases.

Unlike most leading causes of death in the United States, suicide rates have not declined during the past 50 years.1 Among young people the situation is even more dramatic, because suicide rates are rising,2 and suicide is now the second cause of death in 15- to 29-year-olds globally.3 It has been suggested that descriptions of suicide in the media might affect behavior and that the young might be more vulnerable to this effect.4.

There is a renewed interest in better conceptualizing trajectories of Attention-Deficit/Hyperactivity Disorder (ADHD) from childhood to adulthood, driven by an\ud increased recognition of long-term impairment and potential persistence beyond childhood and adolescence. This review addresses the following major issues relevant to the course of ADHD in light of current evidence from longitudinal studies: 1) conceptual and methodological issues related to measurement of persistence of ADHD; 2) estimates of persistence rate from childhood to adulthood and its predictors; 3) long-term negative outcomes of childhood\ud ADHD and their early predictors, and 4) the recently proposed new adult-onset ADHD. Estimates of persistence vary widely in the literature, and diagnostic criteria, sample characteristics and information source are the most important factors explaining variability among studies. Evidence indicates that ADHD severity, comorbid conduct disorder and major depressive disorder, and treatment for ADHD are the main predictors of ADHD persistence from\ud childhood to adulthood. Comorbid conduct disorder and ADHD severity in childhood are the most important predictors of adverse outcomes in adulthood among children with ADHD. Three recent population studies suggested the existence of a significant proportion of individuals who report onset of ADHD symptoms and impairments after childhood. Finally, we highlight areas for improvement to increase our understanding of ADHD across the life span.

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 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.

Neurofeedback (NF) is a training to enhance self-regulatory capacity over brain activity patterns and consequently over brain mental states. Recent findings suggest that NF is a promising alternative for the treatment of attention-deficit/hyperactivity disorder (ADHD). We comprehensively reviewed literature searching for studies on the effectiveness and specificity of NF for the treatment of ADHD. In addition, clinically informative evidence-based data are discussed. We found 3 systematic review on the use of NF for ADHD and 6 randomized controlled trials that have not been included in these reviews. Most nonrandomized controlled trials found positive results with medium-to-large effect sizes, but the evidence for effectiveness are less robust when only randomized controlled studies are considered. The direct comparison of NF and sham-NF in 3 published studies have found no group differences, nevertheless methodological caveats, such as the quality of the training protocol used, sample size, and sample selection may have contributed to the negative results. Further data on specificity comes from electrophysiological studies reporting that NF effectively changes brain activity patterns. No safety issues have emerged from clinical trials and NF seems to be well tolerated and accepted. Follow-up studies support long-term effects of NF. Currently there is no available data to guide clinicians on the predictors of response to NF and on optimal treatment protocol. In conclusion, NF is a valid option for the treatment for ADHD, but further evidence is required to guide its use.

BackgroundCourse and predictors of persistence of attention deficit hyperactivity disorder (ADHD) in adults are still largely unknown. Neurobiological and clinical differences between child and adult ADHD raise the need for follow-up studies of patients diagnosed during adulthood. This study investigates predictors of ADHD persistence and the possibility of full remission 7 years after baseline assessment.MethodA 7-year follow-up study of adults with ADHD (n = 344, mean age 34.1 years, 49.9% males) was conducted. Variables from different domains (social demographics, co-morbidities, temperament, medication status, ADHD measures) were explored with the aim of finding potential predictors of ADHD persistence.ResultsRetention rate was 66% (n = 227). Approximately a third of the sample (n = 70, 30.2%) did not maintain ADHD criteria and 28 (12.4%) presented full remission (p p = 0.01), oppositional defiant disorder (OR 3.12, 95% CI 1.20–8.11, p = 0.02), and social phobia (OR 3.59, 95% CI 1.12–11.47, p = 0.03).ConclusionsDespite the stage of brain maturation in adults suggests stability, approximately one third of the sample did not keep full DSM-IV diagnosis at follow-up, regardless if at early, middle or older adulthood. Although full remission is less common than in childhood, it should be considered as a possible outcome among adults.

To evaluate the long-term effects of methylphenidate imediate-release (MPH-IR), and to confirm the efficacy established in previous meta-analyses of short-term studies.Published and unpublished studies in which participants were treated with MPH-IR for 12 weeks or more were searched. Pooled effect sizes from these studies were computed with the DerSimonian and Laird random-effect model. Meta-regression analysis was conducted to estimate covariates associated with treatment effects.Seven studies were included. Pooled parents ratings for inattention and hyperactivity/impulsivity resulted in standardized mean difference (SMD) = 0.96 (95% confidence interval [CI] = [0.60, 1.32]) and SMD = 1.12 (95% CI = [0.85, 1.39]), respectively; pooled teachers ratings showed SMD = 0.98 (95% CI = [0.09, 1.86]) for inattention and SMD = 1.25 (95% CI = [0.7, 1.81]) for hyperactivity/impulsivity. No evidence of association of any covariates with treatment effect was detected in the meta-regression.MPH-IR is efficacious for childhood ADHD for periods longer than 12 weeks.

Background The literature on the prevalence of mental disorders affecting children and adolescents has expanded significantly over the last three decades around the world. Despite the field having matured significantly, there has been no meta-analysis to calculate a worldwide-pooled prevalence and to empirically assess the sources of heterogeneity of estimates. Methods We conducted a systematic review of the literature searching in PubMed, PsycINFO, and EMBASE for prevalence studies of mental disorders investigating probabilistic community samples of children and adolescents with standardized assessments methods that derive diagnoses according to the DSM or ICD. Meta-analytical techniques were used to estimate the prevalence rates of any mental disorder and individual diagnostic groups. A meta-regression analysis was performed to estimate the effect of population and sample characteristics, study methods, assessment procedures, and case definition in determining the heterogeneity of estimates. Results We included 41 studies conducted in 27 countries from every world region. The worldwide-pooled prevalence of mental disorders was 13.4% (CI 95% 11.3–15.9). The worldwide prevalence of any anxiety disorder was 6.5% (CI 95% 4.7–9.1), any depressive disorder was 2.6% (CI 95% 1.7–3.9), attention-deficit hyperactivity disorder was 3.4% (CI 95% 2.6–4.5), and any disruptive disorder was 5.7% (CI 95% 4.0–8.1). Significant heterogeneity was detected for all pooled estimates. The multivariate metaregression analyses indicated that sample representativeness, sample frame, and diagnostic interview were significant moderators of prevalence estimates. Estimates did not vary as a function of geographic location of studies and year of data collection. The multivariate model explained 88.89% of prevalence heterogeneity, but residual heterogeneity was still significant. Additional meta-analysis detected significant pooled difference in prevalence rates according to requirement of funcional impairment for the diagnosis of mental disorders. Conclusions Our findings suggest that mental disorders affect a significant number of children and adolescents worldwide. The pooled prevalence estimates and the identification of sources of heterogeneity have important implications to service, training, and research planning around the world.

Objective: Few studies assessed factors associated with the agreement/disagreement between fathers and mothers when rating ADHD symptoms of their offspring. Method: Teachers and both parents assessed a referred sample of 98 children and adolescents aged 6 to 16 years ( M age = 9.79, SD = 2.59) using the Swanson, Nolan, and Pelham (SNAP-IV) rating scale. The agreement was assessed for each of the items of the scale and correlated with variables measuring children’s features, socioeconomic adversity, family functioning, and parental psychopathology. Results: Mean agreement between parents was moderate for the inattentive and good for the hyperactive-impulsive construct. Mothers tended to report more symptoms than fathers. The agreement was lower in those families where parents had discrepant educational levels. Conclusion: Our findings suggest a significant cross-informant disagreement between parents on symptoms of ADHD. Discrepant parental education has a relevant role in explaining parental disagreement in reporting ADHD symptoms.