Attention-deficit hyperactivity disorder Posner, Jonathan; Polanczyk, Guilherme V; Sonuga-Barke, Edmund
The Lancet,
02/2020, Letnik:
395, Številka:
10222
Journal Article
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Attention-deficit hyperactivity disorder (ADHD), like other psychiatric disorders, represents an evolving construct that has been refined and developed over the past several decades in response to ...research into its clinical nature and structure. The clinical presentation and course of the disorder have been extensively characterised. Efficacious medication-based treatments are available and widely used, often alongside complementary psychosocial approaches. However, their effectiveness has been questioned because they might not address the broader clinical needs of many individuals with ADHD, especially over the longer term. Non-pharmacological approaches to treatment have proven less effective than previously thought, whereas scientific and clinical studies are starting to fundamentally challenge current conceptions of the causes of ADHD in ways that might have the potential to alter clinical approaches in the future. In view of this, we first provide an account of the diagnosis, epidemiology, and treatment of ADHD from the perspective of both the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders and the eleventh edition of the International Classification of Diseases. Second, we review the progress in our understanding of the causes and pathophysiology of ADHD on the basis of science over the past decade or so. Finally, using these discoveries, we explore some of the key challenges to both the current models and the treatment of ADHD, and the ways in which these findings can promote new perspectives.
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.
Read the Commentary on this article at doi 10.1111/jcpp.12402
Attention-deficit/hyperactivity disorder (ADHD) is now recognized to occur in adulthood and is associated with a range of negative outcomes. However, less is known about the prospective course of ...ADHD into adulthood, the risk factors for its persistence, and the possibility of its emergence in young adulthood in nonclinical populations.
To investigate childhood risk factors and young adult functioning of individuals with persistent, remitted, and late-onset young adult ADHD.
The study sample was the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative birth cohort of 2232 twins born in England and Wales from January 1, 1994, to December 4, 1995. Evaluation of childhood ADHD (ages 5, 7, 10, and 12 years) included prenatal and perinatal factors, clinical characteristics, and aspects of the family environment. Among participants aged 18 years, ADHD symptoms and associated impairment, overall functioning, and other mental health disorders were examined. Data analysis was conducted from February 19 to September 10, 2015.
Attention-deficit/hyperactivity disorder according to DSM-IV diagnostic criteria in childhood and DSM-5 diagnostic criteria in young adulthood.
Of 2232 participants in the E-Risk Study, 2040 were included in the present analysis. In total, 247 individuals met diagnostic criteria for childhood ADHD; of these, 54 (21.9%) also met diagnostic criteria for the disorder at age 18 years. Persistence was associated with more symptoms (odds ratio OR, 1.11 95% CI, 1.04-1.19) and lower IQ (OR, 0.98 95% CI, 0.95-1.00). At age 18 years, individuals with persistent ADHD had more functional impairment (school/work: OR, 3.30 95% CI, 2.18-5.00, home/with friends: OR, 6.26 95% CI, 3.07-12.76), generalized anxiety disorder (OR, 5.19 95% CI, 2.01-13.38), conduct disorder (OR, 2.03 95% CI, 1.03-3.99), and marijuana dependence (OR, 2.88 95% CI, 1.07-7.71) compared with those whose ADHD remitted. Among 166 individuals with adult ADHD, 112 (67.5%) did not meet criteria for ADHD at any assessment in childhood. Results from logistic regressions indicated that individuals with late-onset ADHD showed fewer externalizing problems (OR, 0.93 95% CI, 0.91-0.96) and higher IQ (OR, 1.04 95% CI, 1.02-1.07) in childhood compared with the persistent group. However, at age 18 years, those with late-onset ADHD demonstrated comparable ADHD symptoms and impairment as well as similarly elevated rates of mental health disorders.
We identified heterogeneity in the DSM-5 young adult ADHD population such that this group consisted of a large, late-onset ADHD group with no childhood diagnosis, and a smaller group with persistent ADHD. The extent to which childhood-onset and late-onset adult ADHD may reflect different causes has implications for genetic studies and treatment of ADHD.
Background: Previous studies have identified significant variability in attention-deficit / hyperactivity disorder (ADHD) prevalence estimates worldwide, largely explained by methodological ...procedures. However, increasing rates of ADHD diagnosis and treatment throughout the past few decades have fuelled concerns about whether the true prevalence of the disorder has increased over time.
Methods: We updated the two most comprehensive systematic reviews on ADHD prevalence available in the literature. Meta-regression analyses were conducted to test the effect of year of study in the context of both methodological variables that determined variability in ADHD prevalence (diagnostic criteria, impairment criterion and source of information), and the geographical location of studies.
Results: We identified 154 original studies and included 135 in the multivariate analysis. Methodological procedures investigated were significantly associated with heterogeneity of studies. Geographical location and year of study were not associated with variability in ADHD prevalence estimates.
Conclusions: Confirming previous findings, variability in ADHD prevalence estimates is mostly explained by methodological characteristics of the studies. In the past three decades, there has been no evidence to suggest an increase in the number of children in the community who meet criteria for ADHD when standardized diagnostic procedures are followed.
To evaluate which early neurocognitive and behavioral precursors are associated with the development of attention-deficit/hyperactivity disorder (ADHD) and whether these are currently targeted in ...early interventions.
We conducted 2 systematic reviews and meta-analyses of empirical studies to examine the following: (1) early-life (0-5 years) neurocognitive and behavioral precursors associated with familial likelihood for ADHD, an early ADHD diagnosis/elevated ADHD symptoms, and/or the presence of later-childhood ADHD; and (2) interventions delivered to children aged 0 to 5 years targeting the identified precursors or measuring these as outcomes. Standardized mean differences (Hedges' g) and pre-post-treatment change scores (SMD) were computed.
A total of 149 studies (165,095 participants) investigating 8 neurocognitive and behavioral domains met inclusion criteria for part 1. Multi-level random-effects meta-analyses on 136 studies revealed significant associations between ADHD and poorer cognitive (g = -0.46 95% CIs: -0.59, -0.33), motor (g = -0.35 CIs: -0.48, -0.21) and language (g = -0.43 CIs: -0.66, -0.19) development, social (g = 0.23 CIs: 0.03, 0.43) and emotional (g = 0.46 CIs: 0.33, 0.58) difficulties, early regulatory (g = 0.30 CIs: 0.18, 0.43) and sleep (g = 0.29 CIs: 0.14, 0.44) problems, sensory atypicalities (g = 0.52 CIs: 0.16, 0.88), elevated activity levels (g = 0.54 CIs: 0.37, 0.72), and executive function difficulties (g = 0.34 CIs: 0.05, 0.64 to -0.87 CIs: -1.35, -0.40). A total of 32 trials (28 randomized, 4 nonrandomized, 3,848 participants) testing early interventions that targeted the identified precursors met inclusion criteria for part 2. Multi-level random-effects meta-analyses on 22 studies revealed significant intervention-related improvements in ADHD symptoms (SMD = 0.43 CIs: 0.22, 0.64) and working memory (SMD = 0.37 CIs: 0.06, 0.69).
Children aged 0 to 5 years with current or later-emerging ADHD are likely to experience difficulties in multiple neurocognitive/behavioral functions. Early interventions show some effectiveness in reducing ADHD symptoms, but their effects on neurocognitive/behavioral difficulties require further study.
Despite a prevailing assumption that adult ADHD is a childhood-onset neurodevelopmental disorder, no prospective longitudinal study has described the childhoods of the adult ADHD population. The ...authors report follow-back analyses of ADHD cases diagnosed in adulthood, alongside follow-forward analyses of ADHD cases diagnosed in childhood, in one cohort.
Participants belonged to a representative birth cohort of 1,037 individuals born in Dunedin, New Zealand, in 1972 and 1973 and followed to age 38, with 95% retention. Symptoms of ADHD, associated clinical features, comorbid disorders, neuropsychological deficits, genome-wide association study-derived polygenic risk, and life impairment indicators were assessed. Data sources were participants, parents, teachers, informants, neuropsychological test results, and administrative records. Adult ADHD diagnoses used DSM-5 criteria, apart from onset age and cross-setting corroboration, which were study outcome measures.
As expected, childhood ADHD had a prevalence of 6% (predominantly male) and was associated with childhood comorbid disorders, neurocognitive deficits, polygenic risk, and residual adult life impairment. Also as expected, adult ADHD had a prevalence of 3% (gender balanced) and was associated with adult substance dependence, adult life impairment, and treatment contact. Unexpectedly, the childhood ADHD and adult ADHD groups comprised virtually nonoverlapping sets; 90% of adult ADHD cases lacked a history of childhood ADHD. Also unexpectedly, the adult ADHD group did not show tested neuropsychological deficits in childhood or adulthood, nor did they show polygenic risk for childhood ADHD.
The findings raise the possibility that adults presenting with the ADHD symptom picture may not have a childhood-onset neurodevelopmental disorder. If this finding is replicated, then the disorder's place in the classification system must be reconsidered, and research must investigate the etiology of adult ADHD.
Clinical guidelines currently recommend practitioners titrate stimulant medications, i.e., methylphenidate (MPH) and amphetamines (AMP), to the dose that maximizes symptom control without eliciting ...intolerable adverse events (AEs) when treating attention-deficit/hyperactivity disorder (ADHD) in school-aged children/adolescents. However, robust evidence-base regarding the effects of doses and dosing strategies of stimulants on clinical outcomes in the treatment of children/adolescents with ADHD is currently lacking and stimulants are often underdosed in clinical practice. To address this gap and provide rigorous evidence-base in relation to the dose and dosing strategy of stimulants, we conducted the largest systematic review and dose-response meta-analysis examining change in ADHD symptoms (efficacy), and treatment discontinuations due to AEs (tolerability) and any reason (acceptability). We conducted one-stage random-effects dose-response meta-analyses examining MPH and AMP separately, stratifying trials based on fixed-dose and flexible-dose design. Daily doses of stimulants were converted to MPH- and AMP-equivalent doses by adjusting for different pharmacokinetics across formulations. We also conducted pairwise meta-analyses to provide indirect comparisons between flexible-dose versus fixed-dose trials. Our study included 65 RCTs involving 7 877 children/adolescents. Meta-analyses of fixed-dose trials for both MPH and AMP demonstrated increased efficacy and increased likelihood of discontinuation due to AEs with increasing doses of stimulants. The incremental benefits of stimulants in terms of efficacy decreased beyond 30 mg of MPH or 20 mg of AMP in fixed-dosed trials. In contrast, meta-analyses of flexible-dose trials for both MPH and AMP demonstrated increased efficacy and reduced likelihood of discontinuations for any reason with increasing stimulant doses. The incremental benefits of stimulants in terms of efficacy remained constant across the FDA-licensed dose range for MPH and AMP in flexible-dose trials. Our results suggest that flexible titration as needed, i.e., considering the presence of ADHD symptoms, and tolerated, i.e., considering the presence of dose-limiting AEs, to higher doses of stimulants is associated with both improved efficacy and acceptability because practitioners can increase/reduce doses based on control of ADHD symptoms/dose-limiting AEs. Although fixed-dose trials that are required by the FDA are valuable to characterize dose-dependency, they may underestimate the true potential benefit of trialing dose-increases of stimulants in clinical practice by not allowing dose adjustment based on response and tolerability. Additional research is required to investigate potential long-term effects of using high doses of stimulants in clinical practice.
The Swanson, Nolan, and Pelham scale version IV (SNAP-IV) is widely used to assess symptoms of attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) in children and ...adolescents. Nevertheless, there is insufficient data to support its use in preschool children. The study had three goals: First, to test the factorial validity of the three correlated-factors model of ADHD and ODD items of the SNAP-IV. Second, to investigate the measurement invariance of the items over time (6-month longitudinal interval) and by sex. Third, to investigate the convergent validity and method-specific influences on ADHD/ODD assessments with respect to multiple raters (parents/teachers) of children’s symptoms. Participants were 618 preschool children (3.5–6 years) at baseline and 6-month follow-up. For model testing, we used confirmatory factor analysis for categorical observed variables. Method and trait effects were examined using the CT-C(M-1) model. The analyses showed partial measurement invariance over time and according to sex. Moreover, strong rater-specific effects were detected. The implication of the results for construct validation of the instrument and clinical assessment of ADHD and ODD traits are discussed.
To test the efficacy of a nurse home visiting program (HVP) on child development, maternal and environmental outcomes in the first years of life. We conducted a randomized controlled trial to test ...the efficacy of Primeiros Laços, a nurse HVP for adolescent mothers living in a poor urban area of São Paulo, Brazil. Eighty adolescent mothers were included and randomized to receive either Primeiros Laços (intervention group, n = 40) or healthcare as usual (control group, n = 40). Primeiros Laços is a home visiting intervention delivered by trained nurses that starts during the first 16 weeks of pregnancy and continues to the child's age of 24 months. Participants were assessed by blind interviewers at 8-16 weeks of pregnancy (baseline), 30 weeks of pregnancy, and 3, 6, 12, and 24 months of child's age. We assessed oscillatory power in the mid-range alpha frequency via electroencephalography when the children were aged 6 months. Child development was measured by the Bayley Scales of Infant Development Third Edition (BSID-III). Weight and length were measured by trained professionals and anthropometric indexes were calculated. The home environment and maternal interaction with the child was measured by the Home Observation and Measurement of the Environment. Generalized estimating equation models were used to examine intervention effects on the trajectories of outcomes. Standardized effect sizes (Cohen's d) were calculated using marginal means from endpoint assessments of all outcomes. The trial was registered at clinicaltrial.gov: NCT02807818. Our analyses showed significant positive effects of the intervention on child expressive language development (coefficient = 0.89, 95% CI 0.18, 1.61, p = 0.014), maternal emotional/verbal responsivity (coefficient = 0.97, 95% CI 0.37, 1.58, p = 0.002), and opportunities for variety in daily stimulation (coefficient = 0.37, 95% CI 0.09, 0.66, p = 0.009). Standardized effect sizes of the intervention were small to moderate. Primeiros Laços is a promising intervention to promote child development and to improve the home environment of low-income adolescent mothers. However, considering the limitations of our study, future studies should be conducted to assess Primeiros Laços potential to benefit this population.Clinical Trial Registration: The study was registered at clinicaltrial.gov (Registration date: 21/06/2016 and Registration number: NCT02807818).
Attention-deficit hyperactivity disorder (ADHD) is associated with poorer cognitive functioning. We used a developmental, genetically-sensitive approach to examine intelligence quotient (IQ) from ...early childhood to young adulthood among those with different ADHD courses to investigate whether changes in ADHD were reflected in differences in IQ. We also examined executive functioning in childhood and young adulthood among different ADHD courses.
Study participants were part of the Environmental Risk (E-Risk) Longitudinal Twin Study, a population-based birth cohort of 2232 twins. We assessed ADHD in childhood (ages 5, 7, 10 and 12) and young adulthood (age 18). We examined ADHD course as reflected by remission, persistence and late-onset. IQ was evaluated at ages 5, 12 and 18, and executive functioning at ages 5 and 18.
ADHD groups showed deficits in IQ across development compared to controls; those with persistent ADHD showed the greatest deficit, followed by remitted and late-onset. ADHD groups did not differ from controls in developmental trajectory of IQ, suggesting changes in ADHD were not reflected in IQ. All ADHD groups performed more poorly on executive functioning tasks at ages 5 and 18; persisters and remitters differed only on an inhibitory control task at age 18.
Differences in ADHD course - persistence, remission and late-onset - were not directly reflected in changes in IQ. Instead, having ADHD at any point across development was associated with lower average IQ and poorer executive functioning. Our finding that individuals with persistent ADHD have poorer response inhibition than those who remitted requires replication.
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