Christian Kieling

Child and adolescent mental health worldwide: evidence for action

Mental health problems affect 10-20% of children and adolescents worldwide. Despite their relevance as a leading cause of health-related disability in this age group and their longlasting effects throughout life, the mental health needs of children and adolescents are neglected, especially in low-income and middle-income countries. In this report we review the evidence and the gaps in the published work in terms of prevalence, risk and protective factors, and interventions to prevent and treat childhood and adolescent mental health problems. We also discuss barriers to, and approaches for, the implementation of such strategies in low-resource settings. Action is imperative to reduce the burden of mental health problems in future generations and to allow for the full development of vulnerable children and adolescents worldwide.

ADHD prevalence estimates across three decades: an updated systematic review and meta-regression analysis

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.

The Age at Onset of Attention Deficit Hyperactivity Disorder

Whilst the contemporary concept of attention deficit/hyperactivity disorder (ADHD) is relatively recent, the typical pattern of ADHD symptoms has been described in the literature since the nineteenth century, and these early descriptions all emphasised an onset early in life. ADHD symptoms and impairments are often present during the preschool period. However making a diagnosis during this period is challenging due to the greater variability in normal behaviours during this developmental period. The ADHD construct has been refined over time, and with the introduction of the DSM and ICD classification systems, an age of onset (AOO) criterion was introduced making it a requirement that symptoms, and later on impairment, were present before the age of 7 years. This criterion was challenged as arbitrary and lacking empirical support. In DSM-5 the AOO criterion for ADHD was adjusted such that only some symptoms appearing before the age of 12 years are required to make a diagnosis. ADHD was traditionally thought of as a disorder of childhood, and perhaps adolescence. It is now clear that ADHD often persists into adulthood, either as the full disorder or partially remitted but with continuing impairment. Several recent studies have challenged the notion that ADHD always begins in childhood. Four large community studies have identified a group of adults who did not have ADHD as children but who do meet diagnostic criteria for ADHD as adults. These findings have resulted in considerable debate, and several lines of argument have been put forward to explain the findings.

Neurobiology of Attention Deficit Hyperactivity Disorder

This article addresses the current understanding of the neurobiological bases of attention deficit hyperactivity disorder (ADHD), focusing on empiric research findings that connect genetic and environmental factors to structural and functional brain abnormalities, ultimately leading to a set of age-dependent behavioral manifestations. Section one presents evidence for genetic risk factors for ADHD and discusses the role of potential environmental factors in the etiology of the disorder. Section two focuses on brain imaging studies and how they have helped generate different hypotheses regarding the pathophysiology of ADHD. Finally, the article addresses the longitudinal course of symptoms in ADHD from infancy to adulthood in an attempt to place biological findings for this complex brain disorder in the context of maturation and development.

Attention-deficit/hyperactivity disorder and the dopaminergic hypotheses

Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric condition that affects approximately 5.3% of children worldwide. This disorder is defined by a combination of symptoms of inattention and hyperactivity/impulsivity. Diagnosis is based on impairment in these two domains determining several problems in personal and academic life. Although it is known that genetic and environmental factors are important in ADHD etiology, how these factors influence the brain and consequently behavior is still under debate. There seems to be a consensus in the literature that a fronto-subcortical dysfunction is responsible, at least in part, for the ADHD spectrum. Considering that these brain regions are rich in dopamine (DA), the DA hypothesis has an important role to understand ADHD pathophysiology. The main goal of the present review is to show evidence from different areas that support the idea that dysregulation in the DA system underlies ADHD. We discuss here evidences from animal models, pharmacology, brain imaging and genetics studies.

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

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

Improving access to care for children with mental disorders: a global perspective

Developmental disabilities, emotional disorders and disruptive behaviour disorders are the leading mental health-related causes of the global burden of disease in children aged below 10 years. This article aims to address the treatment gap for child mental disorders through synthesising three bodies of evidence: the global evidence base on the treatment of these priority disorders; the barriers to implementation of this knowledge; and the innovative approaches taken to address these barriers and improve access to care. Our focus is on low-resource settings, which are mostly found in low- and middle-income countries (LMIC). Despite the evidence base on the burden of child mental disorders and their long-term consequences, and the recent mental health Gap Action Programme guidelines which testify to the effectiveness of a range of pharmacological and psychosocial interventions for these disorders, the vast majority of children in LMIC do not have access to these interventions. We identify three major barriers for the implementation of efficacious treatments: the lack of evidence on delivery of the treatments, the low levels of detection of child mental disorders and the shortage of skilled child mental health professionals. The evidence based on implementation, although weak, supports the use of screening measures for detection of probable disorders, coupled with a second-stage diagnostic assessment and the use of non-specialist workers in community and school settings for the delivery of psychosocial interventions. The most viable strategy to address the treatment gap is through the empowerment of existing human resources who are most intimately concerned with child care, including parents, through innovative technologies, such as mobile health, with the necessary skills for the detection and treatment of child mental disorders.

Association between DRD4 gene and performance of children with ADHD in a test of sustained attention.

BACKGROUND The adoption of neuropsychological tests as endophenotypic measures can provide an increased sensitivity to specific dimensions of attention-deficit/hyperactivity disorder (ADHD). METHODS The association between a variable number of tandem repeats polymorphism at the dopamine D4 receptor gene (DRD4) and the performance of children and adolescents with ADHD in a continuous performance test (CPT) was evaluated. The sample comprised 90 clinically referred children and adolescents with ADHD. Errors of omission and commission in the CPT were computed and the number of 48-base pairs tandem repeats in the exon III of DRD4 was assessed. RESULTS The presence of a 7-repeat allele was associated with more errors of commission and the homozygosity of the 4-repeat allele was related to fewer errors of commission and omission even after adjusting for age. CONCLUSIONS These findings bring further evidence on the role of DRD4 polymorphisms on the performance in sustained attention tasks among children and adolescents with ADHD diagnosis.

A current update on ADHD pharmacogenomics

Pharmacological treatment for attention deficit hyperactivity disorder, although highly effective, presents a marked variability in clinical response, optimal dosage needed and tolerability. Clinical and neurobiological investigations have juxtaposed findings on both response to medication and etiologic factors, generating the hypothesis that genetic factors may underlie differences in treatment outcome. Over the last decade, research has focused on the catecholaminergic system to investigate a potential role of genotype on pharmacological effect. Despite an increasing number of associations reported (for methylphenidate, nine in 2005, 24 in 2008 and 52 reported in the current article), the identification of clinically relevant genetic predictors of treatment response remains a challenge. At present, additional studies are required to allow for a shift from a trial-and-error approach to a more rational pharmacologic regimen that takes into account the likelihood of treatment effectiveness at the individual level.

The −1021 C/T DBH polymorphism is associated with neuropsychological performance among children and adolescents with ADHD†

Catecholaminergic imbalance has increasingly been implicated in the pathophysiology of attention‐deficit/hyperactivity disorder (ADHD). The enzyme dopamine‐β‐hydroxylase (DβH)—critical to catecholaminergic regulation—is under strong genetic control, with the −1021 C/T polymorphism accounting for up to 50% of the enzymatic activity. This work aimed to investigate association between this functional polymorphism and the performance of children and adolescents with ADHD in neuropsychological measures of executive function (EF). Sixty‐four drug‐naïve patients with ADHD undertook a Continuous Performance Test and the Wisconsin Card Sorting Test. By means of a factorial analysis, a composite measure of EF was extracted. Performance according to genotypic group was analyzed, including age as a confounder. In addition, a family‐based association test was conducted as a confirmatory analysis. Principal components analysis of neuropsychological measures loaded two factors that explained 83.8% of total variance. Cognitive performance, as measured by the composite score, showed significant difference between genotypic groups after adjustment for age (P = 0.002). The CC homozygosity was associated with a diminished global EF performance, a result that was corroborated by the intra‐familial analysis. The present study demonstrated an association between the neuropsychological performance of children with ADHD and a functional polymorphism in the promoter region of the DBH gene. The refinement of the ADHD phenotype by means of composite measures of EF can contribute to uncover the molecular underpinnings of ADHD.