Does more schooling cause higher lifetime earnings? Social scientists have long sought to determine the economic returns to schooling given its importance to individual life chances and public policy. Prior estimates are limited by unobserved confounding in observational studies and the focus of popular quasi-experimental studies on increases in schooling at only one particular age. Genotyped data offer an opportunity to address unobserved confounding and to estimate the returns to an additional year of schooling at any age by using quasi-randomly assigned genetic variants related to education as instrumental variables [Mendelian randomization (MR)]. We analyze comprehensive Norwegian population registries with career-long earnings data and genotyped data from the Norwegian Mother, Father and Child Cohort Study (MoBa). We employ three identification strategies for triangulation: ordinary least squares (OLS) with covariate-adjustment, sibling and twin fixed-effects models, and MR. Estimated returns to schooling are 8.0% in MR (N = 109,800) and 6.3% in sibling-MR (N = 18,666). Extensive sensitivity analyses suggest that MR results are robust even to large potential violations of MR assumptions, including pleiotropy. MR estimates somewhat higher returns than OLS for the full population (5.9%, N = 1,255,604) and fixed-effects models for siblings (5.3%, N = 966,976) or monozygotic twins (3.2%, N = 2,630). The estimated internal rate of return to schooling exceeds opportunity costs of education as proxied by the market interest rate. The lifetime returns to schooling are positive and substantial across all models.

BACKGROUND:Children and adolescents with attention-deficit hyperactivity disorder (ADHD) have a higher likelihood of contact with child welfare services (CWS). Evidence on whether pharmacological treatment of ADHD reduces such contact is limited. AIMS:To estimate the causal effect of pharmacological treatment of ADHD on CWS contact. METHOD:In this quasi-experimental study, we used nationwide registry data covering all individuals aged 5-14 years and diagnosed with ADHD during 2009-2011 in Norway. We used linear probability models and instrument variable analyses to estimate the associations and causal effects of pharmacological treatment on CWS contact up to 4 years after diagnosis. As instrument variable analysis uses natural variation in treatment decisions between clinics as pseudo-randomisation, estimates inform effects for children and adolescents at the margin of treatment, i.e. patients whose treatment is more influenced by variation in treatment practice, e.g. due to less severe or atypical symptom presentation. RESULTS:A total of 5930 children and adolescents aged 5-14 years were diagnosed with ADHD between 2009 and 2011 (mean (s.d.) age 10.1 (2.4) years; 4380 males (73.9%)). Instrument variable analyses showed a reducing effect of pharmacological treatment on the use of supportive interventions by 11.9 percentage points (95% CI: -20.12, -3.80) and out-of-home-placement by 3.30 percentage points (95% CI: -6.44, -0.15) at 2-year follow-up. This corresponds to the numbers needed to treat estimates of 8 and 30, respectively. CONCLUSIONS:Pharmacological treatment of ADHD reduces CWS contact among children and adolescents at the margin of treatment, lowering the probability of receiving supportive interventions and out-of-home placements. Findings suggest that medication reduces behavioural symptoms, which may improve the family coping mechanism and reduces the need for CWS involvement. TRIAL REGISTRATION:ISRCTN11891971.

Children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and their parents often face challenges that may lead to contact with child welfare services (CWS). However, there is a lack of studies addressing this issue. This study assessed the rate and association between ADHD and different types of CWS contact compared to the general population. We also examined whether individual and parental characteristics were associated with CWS contact among children and adolescents with ADHD. We employed a longitudinal research design and examined an 18-year age trajectory for a cohort of 8,051 children and adolescents aged 5 to 18 years diagnosed with ADHD between 2009 and 2011, linking several Norwegian nationwide registries. Descriptive statistics and logistic regression analysis assessed rate and association between ADHD and CWS contact. Chi-square tests and t-tests examined associations between individual and parental characteristics and CWS contact among those with ADHD. Children and adolescents with ADHD had considerably higher rate of any CWS contacts (32.7%) compared to the general population (6.1%). ADHD was significantly associated with both out-of-home placement (aOR = 7.3, 95% CI: 5.2–10.2) and supportive interventions (aOR = 6.3, 95% CI: 5.1–7.7). Among those with ADHD, comorbid conduct disorder and a criminal record were significantly associated with CWS contact compared to those without CWS contact. Additionally, they were more likely to have unmarried parents and parents with lower income and educational level. These findings provide novel insight into the relationship between ADHD and contact with CWS. Future research should examine the impact of clinical and behavioral treatment of ADHD on contact with CWS.

Background Psychiatric comorbidity is frequent among persons with attention-deficit/hyperactivity disorder (ADHD). Whether pharmacological treatment of ADHD influences the incidence of psychiatric comorbidity is uncertain. Objective To investigate associations and causal relations between pharmacological treatment of ADHD and incidence of subsequent comorbid psychiatric diagnoses. Methods We employed registry data covering all individuals aged 5-18 years in Norway who were diagnosed with ADHD during 2009-2011 (n=8051), followed until 2020. We used linear probability models (LPM) and instrumental variable (IV) analyses to examine associations and causal effects, respectively, between pharmacological treatment and subsequent comorbidity. Findings From time of ADHD diagnosis to 9 years of follow-up, 63% of patients were registered with comorbid psychiatric disorders. For males, LPM showed associations between ADHD medication and several incident comorbidities, but strength and direction of associations and consistency over time varied. For females, no associations were statistically significant. IV analyses for selected categories isolating effects among patients 'on the margin of treatment' showed a protective effect for a category of stress-related disorders in females and for tic disorders in males for the first 2 and 3 years of pharmacological treatment, respectively. Conclusions Overall, LPM and IV analyses did not provide consistent or credible support for long-term effects of pharmacological treatment on later psychiatric comorbidity. However, IV results suggest that for patients on the margin of treatment, pharmacological treatment may initially reduce the incidence of certain categories of comorbid disorders. Clinical implications Clinicians working with persons with ADHD should monitor the effects of ADHD medication on later psychiatric comorbidity. Trial registration number ISRCTN11891971.

Objective: Criminality rates are higher among persons with attention-de fi cit/hyperactivity disorder (ADHD), and evidence that medication reduces crime is limited. Medication rates between clinics vary widely even within universal health care systems, partly because of providers ' treatment preferences. We used this variation to estimate causal effects of pharmacological treatment of ADHD on 4 -year criminal outcomes. Method: We used Norwegian population-level registry data to identify all unique patients aged 10 to 18 years diagnosed with ADHD between 2009 and 2011 (n = 5,624), their use of ADHD medication, and subsequent criminal charges. An instrumental variable design, exploiting variation in provider preference for ADHD medication between clinics, was used to identify causal effects of ADHD medication on crime among patients on the margin of treatment, that is, patients who receive treatment because of their provider ' s preference. Results: Criminality was higher in patients with ADHD relative to the general population. Medication preference varied between clinics and strongly affected patients ' treatment. Instrumental variable analyses supported a protective effect of pharmacological treatment on violence-related and publicorder - related charges with numbers needed to treat of 14 and 8, respectively. There was no evidence for effects on drug-, traff i c-, sexual-, or propertyrelated charges. Conclusion: This is the fi rst study to demonstrate causal effects of pharmacological treatment of ADHD on some types of crimes in a populationbased natural experiment. Pharmacological treatment of ADHD reduced crime related to impulsive-reactive behavior in patients with ADHD on the margin of treatment. No effects were found on crimes requiring criminal intent, conspiracy, and planning. Study preregistration information: The ADHD controversy project: Long-term effects of ADHD medication; https://www.isrctn.com/; 11891971.

Prevalence and medication rates of ADHD vary geographically, both between and within countries. No absolute cutoff exists between ADHD and normal behavior, making clinician attitudes (leading to local practice cultures) a potential explanation for the observed variation in diagnosis and medication rates. The objective of this study was to describe variation in attitudes toward diagnosis and medication of ADHD among clinicians working in child and adolescent mental health services (CAMHS). We hypothesized that attitudes would vary along a spectrum from “restrictive” to “liberal”. We also explored whether differences in attitudes between clinicians were related to professional background and workplace (clinic). A survey in the form of a web-based questionnaire was developed. All CAMHS outpatient clinics in Norway were invited. Potential respondents were all clinicians involved in diagnosing and treating children and adolescents with ADHD. To investigate the existence of attitudes toward diagnosis and medication as latent constructs, we applied confirmatory factor analysis (CFA). We further examined how much of variance in attitudes could be ascribed to profession and clinics by estimating intraclass correlation coefficients. In total, 674 respondents representing 77 (88%) of the clinics participated. We confirmed variation in attitudes with average responses leaning toward the “restrictive” end of the spectrum. CFA supported “attitude toward diagnosis” and “attitude toward medication” as separate, and moderately correlated ( r = 0.4) latent variables, representing a scale from restrictive to liberal. Professional background and workplace explained only a small part of variance in these attitudes.

OBJECTIVE:Criminality rates are higher among persons with attention-deficit/hyperactivity disorder (ADHD), and evidence that medication reduces crime is limited. Medication rates between clinics vary widely even within universal health care systems, partly because of providers' treatment preferences. We used this variation to estimate causal effects of pharmacological treatment of ADHD on 4-year criminal outcomes. METHOD:We used Norwegian population-level registry data to identify all unique patients aged 10 to 18 years diagnosed with ADHD between 2009 and 2011 (n = 5,624), their use of ADHD medication, and subsequent criminal charges. An instrumental variable design, exploiting variation in provider preference for ADHD medication between clinics, was used to identify causal effects of ADHD medication on crime among patients on the margin of treatment, that is, patients who receive treatment because of their provider's preference. RESULTS:Criminality was higher in patients with ADHD relative to the general population. Medication preference varied between clinics and strongly affected patients' treatment. Instrumental variable analyses supported a protective effect of pharmacological treatment on violence-related and public-order-related charges with numbers needed to treat of 14 and 8, respectively. There was no evidence for effects on drug-, traffic-, sexual-, or property-related charges. CONCLUSION:This is the first study to demonstrate causal effects of pharmacological treatment of ADHD on some types of crimes in a population-based natural experiment. Pharmacological treatment of ADHD reduced crime related to impulsive-reactive behavior in patients with ADHD on the margin of treatment. No effects were found on crimes requiring criminal intent, conspiracy, and planning. STUDY PREREGISTRATION INFORMATION:The ADHD controversy project: Long-term effects of ADHD medication; https://www.isrctn.com/; 11891971.

OBJECTIVES:Compulsory mental health care includes compulsory hospitalisation and outpatient commitment with medication treatment without consent. Uncertain evidence of the effects of compulsory care contributes to large geographical variations and a controversy on its use. Some argue that compulsion can rarely be justified and should be reduced to an absolute minimum, while others claim compulsion can more frequently be justified. The limited evidence base has contributed to variations in care that raise issues about the quality/appropriateness of care as well as ethical concerns. To address the question whether compulsory mental health care results in superior, worse or equivalent outcomes for patients, this project will utilise registry-based longitudinal data to examine the effect of compulsory inpatient and outpatient care on multiple outcomes, including suicide and overall mortality; emergency care/injuries; crime and victimisation; and participation in the labour force and welfare dependency. METHODS:By using the natural variation in health providers' preference for compulsory care as a source of quasi-randomisation we will estimate causal effects of compulsory care on short- and long-term trajectories. CONCLUSIONS:This project will provide valuable insights for service providers and policy makers in facilitating high quality clinical care pathways for a high risk population group.

ADHD is associated with an increased risk of injury. Causal evidence for effects of pharmacological treatment on injuries is scarce. We estimated effects of ADHD medication on injuries using variation in provider preference as an instrumental variable (IV). Using Norwegian registry data, we followed 8051 patients who were diagnosed with ADHD aged 5 to 18 between 2009 and 2011 and recorded their ADHD medication and injuries treated in emergency rooms and emergency wards up to 4 years after diagnosis. Persons with ADHD had an increased risk of injuries compared to the general population (RR 1.35; 95% CI: 1.30-1.39), with higher risk in females (RR 1.47; 95% CI: 1.38-1.56) than males (RR 1.23; 95% CI: 1.18-1.28). The between-clinics variation in provider preference for ADHD medication was large and had a considerable impact on patients' treatment status. There was no causal evidence for protective effects of pharmacological treatment on injuries overall for young individuals with ADHD characterized by milder or atypical symptoms. However, there was an apparent effect of pharmacological treatment over time on the risk of injuries treated at emergency wards in this patient group.

BackgroundThere are now hundreds of systematic reviews on attention deficit hyperactivity disorder (ADHD) of variable quality. To help navigate this literature, we have reviewed systematic reviews on any topic on ADHD.MethodsWe searched MEDLINE, PubMed, PsycINFO, Cochrane Library, and Web of Science and performed quality assessment according to the Joanna Briggs Institute Manual for Evidence Synthesis. A total of 231 systematic reviews and meta-analyses met the eligibility criteria.ResultsThe prevalence of ADHD was 7.2% for children and adolescents and 2.5% for adults, though with major uncertainty due to methodological variation in the existing literature. There is evidence for both biological and social risk factors for ADHD, but this evidence is mostly correlational rather than causal due to confounding and reverse causality. There is strong evidence for the efficacy of pharmacological treatment on symptom reduction in the short-term, particularly for stimulants. However, there is limited evidence for the efficacy of pharmacotherapy in mitigating adverse life trajectories such as educational attainment, employment, substance abuse, injuries, suicides, crime, and comorbid mental and somatic conditions. Pharmacotherapy is linked with side effects like disturbed sleep, reduced appetite, and increased blood pressure, but less is known about potential adverse effects after long-term use. Evidence of the efficacy of nonpharmacological treatments is mixed.ConclusionsDespite hundreds of systematic reviews on ADHD, key questions are still unanswered. Evidence gaps remain as to a more accurate prevalence of ADHD, whether documented risk factors are causal, the efficacy of nonpharmacological treatments on any outcomes, and pharmacotherapy in mitigating the adverse outcomes associated with ADHD.

Instrumental variables (IV) is a central strategy for identifying causal effects in absence of randomized experiments. Clinicians and epidemiologists may find the intuition of IV easy to grasp by comparison to randomized experiments. Randomization is an ideal IV because treatment is assigned randomly, and hence unaffected by everything else. IV methods in nonexperimental settings mimic a randomized experiment by using a source of “as good as” random variation in treatment instead. The main challenge with IV designs is to find IVs that are as good as randomization. Discovering potential IVs require substantive knowledge and an understanding of design principles. Moreover, IV methods recover causal effects for a subset of the population who take treatment when induced by the IV. Sometimes these estimates are informative, other times their relevance is questionable. We provide an introduction to IV methods in clinical epidemiology. First, we introduce the main principles and assumptions. Second, we present practical examples based on Mendelian randomization and provider preference and refer to other common IVs in health. Third, practical steps in IV analysis are presented. Fourth, the promise and perils of IV methods are discussed. Finally, we suggest further readings.

Instrumental variables (IV) is a central strategy for identifying causal effects in absence of randomized experiments. Clinicians and ep-idemiologists may find the intuition of IV easy to grasp by comparison to randomized experiments. Randomization is an ideal IV because treatment is assigned randomly, and hence unaffected by everything else. IV methods in nonexperimental settings mimic a randomized experiment by using a source of "as good as "random variation in treatment instead. The main challenge with IV designs is to find IVs that are as good as randomization. Discovering potential IVs require substantive knowledge and an understanding of design principles. Moreover, IV methods recover causal effects for a subset of the population who take treatment when induced by the IV. Sometimes these estimates are informative, other times their relevance is questionable. We provide an introduction to IV methods in clinical epidemiology. First, we introduce the main principles and assumptions. Second, we present practical examples based on Mendelian randomization and provider preference and refer to other common IVs in health. Third, practical steps in IV analysis are presented. Fourth, the promise and perils of IV methods are discussed. Finally, we suggest further readings.(c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Rates of ADHD diagnosis vary across regions in many countries. However, no prior study has investigated how much within-country geographic variation in ADHD diagnoses is explained by variation in ADHD symptom levels. We examine whether ADHD symptom levels explain variation in ADHD diagnoses among children and adolescents using nationwide survey and register data in Norway. Geographical variation in incidence of ADHD diagnosis was measured using Norwegian registry data from the child and adolescent mental health services for 2011–2016. Geographical variation in ADHD symptom levels in clinics’ catchment areas was measured using data from the Norwegian mother, father and child cohort study for 2011–2016 (n = 39,850). Cross-sectional associations between ADHD symptom levels and the incidence of ADHD diagnoses were assessed with fractional response models. Geographical variation in ADHD diagnosis rates is much larger than what can be explained by geographical variation in ADHD symptoms levels. Treatment in the Norwegian child and adolescent mental health services is free, universally available upon referral, and practically without competition from the private sector. Factors beyond health care access and unequal symptom levels seem responsible for the geographical variation in ADHD diagnosis.

Introduction Attention-deficit/hyperactivity disorder (ADHD) is among the most common mental disorders in children and adolescents, and it is a strong risk factor for several adverse psychosocial outcomes over the lifespan. There are large between-country and within-country variations in diagnosis and medication rates. Due to ethical and practical considerations, a few studies have examined the effects of receiving a diagnosis, and there is a lack of research on effects of medication on long-term outcomes.Our project has four aims organised in four work packages: (WP1) To examine the prognosis of ADHD (with and without medication) compared with patients with other psychiatric diagnoses, patients in contact with public sector child and adolescent psychiatric outpatient clinics (without diagnosis) and the general population; (WP2) Examine within-country variation in ADHD diagnoses and medication rates by clinics’ catchment area; and(WP3) Identify causal effects of being diagnosed with ADHD and (WP4) ADHD medication on long-term outcomes.Method and analysis Our project links several nationwide Norwegian registries. The patient sample is all persons aged 5–18 years that were in contact with public sector child and adolescent psychiatric outpatient clinics in 2009–2011. Our comparative analysis of prognosis will be based on survival analysis and mixed-effects models. Our analysis of variation will apply mixed-effects models and generalised linear models. We have two identification strategies for the effect of being diagnosed with ADHD and of receiving medication on long-term outcomes. Both strategies rely on using preference-based instrumental variables, which in our project are based on provider preferences for ADHD diagnosis and medication.Ethics and dissemination The project is approved by the Regional Ethics Committee, Norway (REC number 2017/2150/REC south-east D). All papers will be published in open-access journals and results will be presented in national and international conferences.Trial registration numbers ISRCTN11573246 and ISRCTN11891971.

OBJECTIVE:Preference-based instrumental variables (PP IV) designs can identify causal effects when patients receive treatment due to variation in providers' treatment preference. We offer a systematic review and methodological assessment of PP IV applications in health research.STUDY DESIGN AND SETTING:We included studies that applied PP IV for evaluation of any treatment in any population in health research (PROSPERO: CRD42020165014). We searched within four databases (Medline, Web of Science, ScienceDirect, SpringerLink) and four journals (including full-text and title and abstract sources) between January 1, 1998, and March 5, 2020. We extracted data on areas of applications and methodology, including assumptions using Swanson and Hernan's (2013) guideline.RESULTS:We included 185 of 1087 identified studies. The use of PP IV has increased, being predominantly used for treatment effects in cancer, cardiovascular disease, and mental health. The most common PP IV was treatment variation at the facility-level, followed by physician- and regional-level. Only 12 percent of applications report the four main assumptions for PP IV. Selection on treatment may be a potential issue in 46 percent of studies.CONCLUSION:The assumptions of PP IV are not sufficiently reported in existing work. PP IV-studies should use reporting guidelines.

Childhood economic conditions are important for adult health, and welfare regimes may modify this relationship by altering exposure to social determinants of health. We examine the association between childhood economic stress (CES) and self-rated health (SRH) and cancer (any type), and how welfare regimes may influence these associations. We used data from European Social Survey round 7. Our study is based on 30 024 individuals between 25 to 75 years from 20 European countries grouped into five welfare regimes (Scandinavian, Anglo-Saxon, Bismarckian, Southern and Eastern). Multilevel models were used to assess the association between CES and SRH/cancer, and interactions between CES and welfare regimes. CES increased the risk of poor SRH (RR 1.41, 95% CI 1.29–1.54) and cancer (RR 1.19, 95% CI 1.02–1.37). Controlling for adult socioeconomic status slightly reduced risk for poor SRH, but not cancer. CES increased the probability of poor SRH in the Southern and Eastern regime, and the probability of cancer in the Anglo-Saxon regime, relative to the Scandinavian regime. Childhood economic stress increases the risk of poor self-rated health and cancer. More comprehensive welfare states mitigate these associations, which emphasizes the impact of welfare policies on long-term health outcomes of childhood economic conditions.