Individualized prediction models in ADHD: a systematic review and meta-regression.

There have been increasing efforts to develop prediction models supporting personalised detection, prediction, or treatment of ADHD. We overviewed the current status of prediction science in ADHD by: (1) systematically reviewing and appraising available prediction models; (2) quantitatively assessing factors impacting the performance of published models. We did a PRISMA/CHARMS/TRIPOD-compliant systematic review (PROSPERO: CRD42023387502), searching, until 20/12/2023, studies reporting internally and/or externally validated diagnostic/prognostic/treatment-response prediction models in ADHD. Using meta-regressions, we explored the impact of factors affecting the area under the curve (AUC) of the models. We assessed the study risk of bias with the Prediction Model Risk of Bias Assessment Tool (PROBAST). From 7764 identified records, 100 prediction models were included (88% diagnostic, 5% prognostic, and 7% treatment-response). Of these, 96% and 7% were internally and externally validated, respectively. None was implemented in clinical practice. Only 8% of the models were deemed at low risk of bias; 67% were considered at high risk of bias. Clinical, neuroimaging, and cognitive predictors were used in 35%, 31%, and 27% of the studies, respectively. The performance of ADHD prediction models was increased in those models including, compared to those models not including, clinical predictors (ß = 6.54, p = 0.007). Type of validation, age range, type of model, number of predictors, study quality, and other type of predictors did not alter the AUC. Several prediction models have been developed to support the diagnosis of ADHD. However, efforts to predict outcomes or treatment response have been limited, and none of the available models is ready for implementation into clinical practice. The use of clinical predictors, which may be combined with other type of predictors, seems to improve the performance of the models. A new generation of research should address these gaps by conducting high quality, replicable, and externally validated models, followed by implementation research.

Understanding priorities and needs for child and adolescent mental health in Greece from multiple informants: an open resource dataset.

The Child and Adolescent Mental Health Initiative (CAMHI) aims to enhance mental health care capacity for children and adolescents across Greece. Considering the need for evidence-based policy, the program developed an open-resource dataset for researching the field within the country. A comprehensive, mixed-method, community-based research was conducted in 2022/2023 assessing the current state, needs, barriers, and opportunities according to multiple viewpoints. We surveyed geographically distributed samples of 1,756 caregivers, 1,201 children/adolescents, 404 schoolteachers, and 475 health professionals using validated instruments to assess mental health symptoms, mental health needs, literacy and stigma, service use and access, professional practices, training background, and training needs and preferences. Fourteen focus groups were conducted with informants from diverse populations (including underrepresented minorities) to reach an in-depth understanding of those topics. A dataset with quantitative and qualitative findings is now available for researchers, policymakers, and society [ https://osf.io/crz6h/ and https://rpubs.com/camhi/sdashboard ]. This resource offers valuable data for assessing the needs and priorities for child and adolescent mental health care in Greece. It is now freely available to consult, and is expected to inform upcoming research and evidence-based professional training. This initiative may inspire similar ones in other countries, informing methodological strategies for researching mental health needs.

Translation and cross-cultural adaptation of seventeen widely-used assessment instruments for child and adolescent mental health in Greece.

BACKGROUND: In the context of Greece, many instruments measuring constructs pertinent to child and adolescent mental health lacked a locally-validated, freely-available version. As part of a nationwide survey, we translated and cross-culturally adapted a collection of seventeen brief, largely-employed assessment tools that can be used at scale. METHODS: This study is part of the Child and Adolescent Mental Health Initiative in Greece (CAMHI), a capacity-building program focusing on enhancing mental health care for children and adolescents living in Greece. We conducted a nationwide survey assessing mental health symptoms, parenting practices, service availability and quality, mental health literacy and stigma, and professional practices within the country. As part of this process, we selected outcomes and instruments after consulting the International Consortium for Health Outcomes Measurement (ICHOM) and the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). From our selection, we identified 17 instruments that did not have a Greek-validated version available for use. These instruments were translated and cross-culturally adapted following a structured procedure, including independent back-and-forth translations, synthesis of versions, expert revision, and pilot testing. Some instruments were slightly modified to meet CAMHI survey purposes. RESULTS: A cross-culturally adapted version in Greek was made available for the following instruments: Pediatric Symptoms Checklist (PSC); Deliberate Self Harm Inventory (DSH) (modified); Child and Adolescent Trauma Screen-2 (CATS-2); ABCD Screen Use (modified); Swanson, Nolan, and Pelham-IV (SNAP-IV); Parent Behavior Inventory (PBI); Mental Health Literacy Scale (MHLS)-(modified); Australian Mental Health Vignettes; Reported and Intended Behavior Scale (RIBS); Barriers to Access to Care (BACE) (modified); Experience of Service Questionnaire (ESQ) (modified); and Multitheoretical List of Therapeutic Interventions (MULTI-30) (modified). CONCLUSION: A collection of these widely-used assessment tools is now adapted for the local context and freely accessible at [ https://osf.io/crz6h/ ]. Researchers and health professionals in Greece can utilize this resource to screen, evaluate, and monitor various constructs related to mental health in accordance with the most effective practices.

Worldwide Prevalence and Disability From Mental Disorders Across Childhood and Adolescence: Evidence From the Global Burden of Disease Study.

Importance: The period from childhood to early adulthood involves increased susceptibility to the onset of mental disorders, with implications for policy making that may be better appreciated by disaggregated analyses of narrow age groups. Objective: To estimate the global prevalence and years lived with disability (YLDs) associated with mental disorders and substance use disorders (SUDs) across 4 age groups using data from the 2019 Global Burden of Disease (GBD) study. Design, Setting, and Participants: Data from the 2019 GBD study were used for analysis of mental disorders and SUDs. Results were stratified by age group (age 5 to 9, 10 to 14, 15 to 19, and 20 to 24 years) and sex. Data for the 2019 GBD study were collected up to 2018, and data were analyzed for this article from April 2022 to September 2023. Exposure: Age 5 to 9 years, 10 to 14 years, 15 to 19 years, and 20 to 24 years. Main Outcomes and Measures: Prevalence rates with 95% uncertainty intervals (95% UIs) and number of YLDs. Results: Globally in 2019, 293 million of 2516 million individuals aged 5 to 24 years had at least 1 mental disorder, and 31 million had an SUD. The mean prevalence was 11.63% for mental disorders and 1.22% for SUDs. For the narrower age groups, the prevalence of mental disorders was 6.80% (95% UI, 5.58-8.03) for those aged 5 to 9 years, 12.40% (95% UI, 10.62-14.59) for those aged 10 to 14 years, 13.96% (95% UI, 12.36-15.78) for those aged 15 to 19 years, and 13.63% (95% UI, 11.90-15.53) for those aged 20 to 24 years. The prevalence of each individual disorder also varied by age groups; sex-specific patterns varied to some extent by age. Mental disorders accounted for 31.14 million of 153.59 million YLDs (20.27% of YLDs from all causes). SUDs accounted for 4.30 million YLDs (2.80% of YLDs from all causes). Over the entire life course, 24.85% of all YLDs attributable to mental disorders were recorded before age 25 years. Conclusions and Relevance: An analytical framework that relies on stratified age groups should be adopted for examination of mental disorders and SUDs from childhood to early adulthood. Given the implications of the early onset and lifetime burden of mental disorders and SUDs, age-disaggregated data are essential for the understanding of vulnerability and effective prevention and intervention initiatives.

ADHD in Mozambique: An epidemiological investigation in a Primary School Sample.

OBJECTIVE: To evaluate the prevalence of ADHD, comorbidity rates with Disruptive Behavior Disorders (DBD), and main negative outcomes in primary-school students in Nampula, Mozambique. METHODS: We selected a random sample of 748 students for ADHD screening from a population of around 43000 primary school students. The Swanson, Nolan, and Pelham Rating Scale version IV (SNAP-IV scale) was applied to both parents and teachers. All positive screened students (n = 76) and a propensity score-matched random subset of negative screened subjects (n = 76) had a psychiatric evaluation carried out by a child psychiatrist. RESULTS: The prevalence of ADHD was estimated to be 13.4% (CI95%: 11.5%-19.2%) and 30.6% of youths with ADHD presented a comorbid DBD. Students with ADHD (n=36) had significantly higher rates of both substance use (alcohol, marijuana) (p < .001), and school repetitions than controls (n=96; p < .001). Comorbidity between ADHD and DBD increased the chance of substance use (p < .001). Secondary analyses, using more restrictive ADHD diagnostic criteria determined a lower prevalence rate (6.7%; CI95%: 5.2%-12.9%) with similar patterns of associated factors and negative outcomes. CONCLUSION: Our findings demonstrated that ADHD is a prevalent mental disorder in Mozambique, and it is associated with similar comorbid profiles, predisposing factors, and negative outcomes as in other cultures.

Exploring Diagnostic Performance of a Screening Instrument for ADHD and DSM-5 Number of Symptoms Criterion in Primary School Students From Mozambique.

OBJECTIVE: To explore the ADHD diagnostic performance of a screening instrument, and which DSM-5 ADHD number of symptoms (criterion A) was best associated with impairment in a sample of students from 106 primary schools in Nampula, Mozambique. METHODS: A random sample of 748 students were assessed using SNAP-IV and 152 youths (76 positive and 76 negative screeners) were invited for psychiatric diagnostic confirmation. RESULTS: The performance of the screening instrument for predicting ADHD diagnosis was poor (all AUCs < 0.53). No other cut-off worked best in predicting impairment than the six symptoms cutoff suggested by DSM-5 for both inattention (AUC = 0.78; 95% CI [0.69, 0.86]) and hyperactivity/impulsivity (AUC = 0.75; 95% CI [0.67, 0.84]). CONCLUSION: Our findings highlight the adequacy of the DSM-5 ADHD criterion A in an African culture but indicate low diagnostic performance of a screening instruments only based in parent or teacher reports on symptoms to predict ADHD diagnosis.

When should a university student be allowed academic accommodations for attention-deficit/hyperactivity disorder? A position statement for a unified procedure for use in Brazil

In higher education, reasonable accommodations are increasingly made for students with a wide range of disabilities. However, rigorous assessment is paramount to ensure these students are supported while preventing ineligible students from gaining unfair advantages. In this context, we sought to identify under which circumstances a university student should be allowed academic accommodation for attention-deficit/hyperactivity disorder (ADHD) and to outline an evidence-based policy for use in Brazil based on the global experience. We reviewed the literature to acquire information on what documents are commonly required by disability services before accommodations for ADHD are provided (including detection of malingering) and scrutinized the eligibility criteria of leading universities worldwide. Finally, renowned experts in the field and national stakeholders were consulted. Despite an exhaustive search, we found no international standard for the assessment of students with ADHD who request academic accommodation; even renowned institutions worldwide differ in their approaches to granting accommodations on the grounds of ADHD. Therefore, we propose a unified set of nationwide criteria for Brazilian universities, which could be generalized internationally. Higher education institutions in Brazil and beyond may benefit from adoption of such criteria.

When should a university student be allowed academic accommodation For ADHD? A position statement for a unified procedure for use in Brazil.

OBJECTIVE: To identify under what circumstances a university student should be allowed academic accommodation for ADHD. To frame an evidence-based policy for use in Brazil based on a worldwide experience. METHODS: We reviewed the literature to acquire information on what documents are commonly required by disability services before accommodation for ADHD is made (including malingering detection). We scrutinized the eligibility criteria of the best universities worldwide. Renowned experts in the field and national stakeholders were consulted. RESULTS: We found no international standard for the assessment of students with ADHD who request academic accommodation. Even renowned institutions worldwide differ from one another in their approaches to academic accommodation on the grounds of ADHD. We propose a national unified set of criteria for Brazilian universities, which could generalize internationally. DISCUSSION: Rigorous assessment is paramount for aiding students with disabilities while preventing ineligible students gaining an unfair advantage. Higher education institutions nationwide and beyond may benefit from adopting a unified set of criteria for eligibility to ADHD accommodation programs.

The science of child and adolescent mental health in Greece: a nationwide systematic review.

Evidence-based information is essential for effective mental health care, yet the extent and accessibility of the scientific literature are critical barriers for professionals and policymakers. To map the necessities and make validated resources accessible, we undertook a systematic review of scientific evidence on child and adolescent mental health in Greece encompassing three research topics: prevalence estimates, assessment instruments, and interventions. We searched Pubmed, Web of Science, PsycINFO, Google Scholar, and IATPOTEK from inception to December 16th, 2021. We included studies assessing the prevalence of conditions, reporting data on assessment tools, and experimental interventions. For each area, manuals informed data extraction and the methodological quality were ascertained using validated tools. This review was registered in protocols.io [68583]. We included 104 studies reporting 533 prevalence estimates, 223 studies informing data on 261 assessment instruments, and 34 intervention studies. We report the prevalence of conditions according to regions within the country. A repository of locally validated instruments and their psychometrics was compiled. An overview of interventions provided data on their effectiveness. The outcomes are made available in an interactive resource online [ https://rpubs.com/camhi/sysrev_table ]. Scientific evidence on child and adolescent mental health in Greece has now been cataloged and appraised. This timely and accessible compendium of up-to-date evidence offers valuable resources for clinical practice and policymaking in Greece and may encourage similar assessments in other countries.

Identifying Depression Early in Adolescence: assessing the performance of a risk score for future onset of depression in an independent Brazilian sample.

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.

The synergistic effect of genetic and environmental factors in the development of attention-deficit/hyperactivity disorder symptoms in children and adolescents.

Gene-environment interactions (GxE) have been increasingly explored in psychiatry but with low replication rates. Attention-deficit/hyperactivity disorder (ADHD) is a suitable candidate for studying GxE due to its high heritability and well-defined environmental risk factors. Here, we explored GxE using polygenic risk score (PRS) to represent the genetic liability to ADHD (ADHD-PRS) and environmental risk score (ERS) to represent the combined effects of environmental risk factors. We analyzed longitudinal data of 2,046 individuals (6-14 years of age at baseline and 14-23 at the last follow-up) from the Brazilian High-Risk Cohort Study for Psychiatric Disorders. Psychiatric evaluation included the Child Behavior Checklist and the Strength and Difficulties Questionnaire. Statistical analyses were performed using mixed-effects models. We observed statistically significant interactions between ADHD-PRS and ERS, suggesting that environmental and genetic factors act synergistically in the development of ADHD symptoms. These effects were not present for depression or anxiety symptoms. No evidence of GxE correlation was detected. Mechanistically, our findings suggest that environmental stressors modulate the genetic risk for ADHD. Future studies should investigate whether the reduction of environmental risks can prevent the development of symptoms of ADHD, especially in children with a family history of the disorder.

Polygenic risk score for attention-deficit/hyperactivity disorder and brain functional networks segregation in a community-based sample.

Neuroimaging studies suggest that brain development mechanisms might explain at least some behavioural and cognitive attention-deficit/hyperactivity disorder (ADHD) symptoms. However, the putative mechanisms by which genetic susceptibility factors influence clinical features via alterations of brain development remain largely unknown. Here, we set out to integrate genomics and connectomics tools by investigating the associations between an ADHD polygenic risk score (ADHD-PRS) and functional segregation of large-scale brain networks. With this aim, ADHD symptoms score, genetic and rs-fMRI (resting-state functional magnetic resonance image) data obtained in a longitudinal community-based cohort of 227 children and adolescents were analysed. A follow-up was conducted approximately 3 years after the baseline, with rs-fMRI scanning and ADHD likelihood assessment in both stages. We hypothesised a negative correlation between probable ADHD and the segregation of networks involved in executive functions, and a positive correlation with the default-mode network (DMN). Our findings suggest that ADHD-PRS is correlated with ADHD at baseline, but not at follow-up. Despite not surviving for multiple comparison correction, we found significant correlations between ADHD-PRS and segregation of cingulo-opercular networks and DMN at baseline. ADHD-PRS was negatively correlated with the segregation level of cingulo-opercular networks but positively correlated with the DMN segregation. These directions of associations corroborate the proposed counter-balanced role of attentional networks and DMN in attentional processes. However, the association between ADHD-PRS and brain networks functional segregation was not found at follow-up. Our results provide evidence for specific influences of genetic factors on development of attentional networks and DMN. We found significant correlations between polygenic risk score for ADHD (ADHD-PRS) and segregation of cingulo-opercular networks and default-mode network (DMN) at baseline. ADHD-PRS was negatively correlated with the segregation level of cingulo-opercular networks but positively correlated with the DMN segregation.

Association between preterm infant size at 1 year and ADHD later in life: data from 1993 and 2004 Pelotas Birth Cohorts.

The objective of this study is to examine the association between preterm infants' size at 1 year and attention-deficit/hyperactivity disorder (ADHD) assessed categorically and dimensionally in childhood and adolescence. We studied infants born < 37 weeks' gestation from two Brazilian birth cohorts (n = 653). ADHD was evaluated using the Development and Well-Being Assessment (DAWBA) interview at the age of 6 years in one cohort and by a structured interview according to DSM-5 criteria at 18 years in the other one. The presence of child attention difficulties was measured by the Strengths and Difficulties Questionnaire (SDQ) at 6 and 11 years in the 2004 and 1993 cohorts, respectively. We estimated associations of weight, length, head circumference, and BMI z-scores at 1-year chronological age with ADHD using Poisson Regression Model; and with attention difficulties using Linear Regression, adjusting for covariates. Mean birth weight was 2500 g and gestational age was 34.5 weeks. The aggregated ADHD prevalence in the two cohorts was 2.7%, and the median score for attention difficulties was 3.0. We found that increased head circumference at 1 year was associated with a lower risk of ADHD diagnosis (RR = 0.7, 95% CI 0.4, 0.9; p = 0.04 per standard deviation difference) and with fewer dimensional attention symptoms. In sensitivity analysis with other mental disorders, head circumference was associated with depression, but not with anxiety. Our findings emphasize poor head growth in the first year of life as a potential determinant of attentional difficulties in the preterm infant population.

Genetic risk for attention-deficit/hyperactivity disorder predicts cognitive decline and development of Alzheimer's disease pathophysiology in cognitively unimpaired older adults.

Attention-deficit/hyperactivity disorder (ADHD) persists in older age and is postulated as a risk factor for cognitive impairment and Alzheimer's Disease (AD). However, these findings rely primarily on electronic health records and can present biased estimates of disease prevalence. An obstacle to investigating age-related cognitive decline in ADHD is the absence of large-scale studies following patients with ADHD into older age. Alternatively, this study aimed to determine whether genetic liability for ADHD, as measured by a well-validated ADHD polygenic risk score (ADHD-PRS), is associated with cognitive decline and the development of AD pathophysiology in cognitively unimpaired (CU) older adults. We calculated a weighted ADHD-PRS in 212 CU individuals without a clinical diagnosis of ADHD (55-90 years). These individuals had baseline amyloid-ß (Aß) positron emission tomography, longitudinal cerebrospinal fluid (CSF) phosphorylated tau at threonine 181 (p-tau181), magnetic resonance imaging, and cognitive assessments for up to 6 years. Linear mixed-effects models were used to test the association of ADHD-PRS with cognition and AD biomarkers. Higher ADHD-PRS was associated with greater cognitive decline over 6 years. The combined effect between high ADHD-PRS and brain Aß deposition on cognitive deterioration was more significant than each individually. Additionally, higher ADHD-PRS was associated with increased CSF p-tau181 levels and frontoparietal atrophy in CU Aß-positive individuals. Our results suggest that genetic liability for ADHD is associated with cognitive deterioration and the development of AD pathophysiology. Findings were mostly observed in Aß-positive individuals, suggesting that the genetic liability for ADHD increases susceptibility to the harmful effects of Aß pathology.

Replication of a predictive model for youth ADHD in an independent sample from a developing country.

BACKGROUND: Very few predictive models in Psychiatry had their performance validated in independent external samples. A previously developed multivariable demographic model for attention-deficit/hyperactivity disorder (ADHD) accurately predicted young adulthood ADHD using clinical and demographical information collected in childhood in three samples from developed countries, but failed to replicate its performance in a sample from a developing country. Furthermore, consolidated risk factors for ADHD were not included among its predictors. METHODS: Participants were 1905 children and adolescents from a community-based sample and followed from ages 6 to 14 years at baseline to ages 14 to 23 years (mean age 18) at follow-up. We applied the intercept and weights of the original model to the data, calculating the predicted probability of each participant according to the set of predictors collected in childhood, and compared the estimates with the actual outcome (ADHD) collected during adolescence and young adulthood. We explored the performance of the original model, and of models including novel predictors (prematurity, family history of ADHD, and polygenic risk score for ADHD). RESULTS: The observed area under the curve of the original model was .76 (95% Confidence Interval .70 to .82). The multivariable demographical model outperformed single variable models using only prematurity, family history, or the ADHD PRS. Adding either of these variables, or all at once, did not improve the performance of the original demographical model. CONCLUSIONS: Our findings suggest that the originally developed ADHD predictive model is suitable for use in different settings for clinical and research purposes.

Identifying Depression Early in Adolescence: assessing the performance of a risk score for future onset of depression in an independent Brazilian sample

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.

Identifying adolescents at risk for depression: Assessment of a global prediction model in the Great Smoky Mountains Study.

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) in an adolescent population-based sample in the United States of America - the Great Smoky Mountains Study (GSMS). We applied the intercept and weights of the original IDEA-RS model developed in Brazil to generate individual probabilities for each participant of the GSMS 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. 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. 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.

Toward Precision Medicine in ADHD.

Attention-Deficit Hyperactivity Disorder (ADHD) is a complex and heterogeneous neurodevelopmental condition for which curative treatments are lacking. Whilst pharmacological treatments are generally effective and safe, there is considerable inter-individual variability among patients regarding treatment response, required dose, and tolerability. Many of the non-pharmacological treatments, which are preferred to drug-treatment by some patients, either lack efficacy for core symptoms or are associated with small effect sizes. No evidence-based decision tools are currently available to allocate pharmacological or psychosocial treatments based on the patient's clinical, environmental, cognitive, genetic, or biological characteristics. We systematically reviewed potential biomarkers that may help in diagnosing ADHD and/or stratifying ADHD into more homogeneous subgroups and/or predict clinical course, treatment response, and long-term outcome across the lifespan. Most work involved exploratory studies with cognitive, actigraphic and EEG diagnostic markers to predict ADHD, along with relatively few studies exploring markers to subtype ADHD and predict response to treatment. There is a critical need for multisite prospective carefully designed experimentally controlled or observational studies to identify biomarkers that index inter-individual variability and/or predict treatment response.

Physical activity and depressive symptoms among adolescents in a school-based sample

Objective: To explore associations between self-reported weekly physical activity and depressive symptomatology among adolescents in a school-based sample from Brazil. Methods: 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. Results: 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, p < 0.001). 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, p < 0.001). Conclusion: In this large sample of Brazilian adolescents, those who exercised less frequently and vigorously than their peers reported more depressive symptoms.