Cigarette smoking is associated with a wide variety of adverse reproductive outcomes, including increased infant mortality and decreased birth weight. Prenatal exposure to tobacco smoke, of which ...nicotine is a major teratogenic component, has also been linked to the acceleration of the risk for different psychiatric disorders, including conduct disorder and attention deficit hyperactivity disorder (ADHD). Whether this increased risk is influenced by the direct effects of gestational nicotine exposure on the developing fetus remains uncertain. In this study we provide experimental evidence for the effects of prenatal nicotine exposure on measures of attention and impulsivity in adult male rats. Offspring of females exposed during pregnancy to 0.06 mg/ml nicotine solution as the only source of water (daily consumption: 69.6±1.4 ml/kg; nicotine blood level: 96.0±31.9 ng/ml) had lower birth weight and delayed sensorimotor development measured by negative geotaxis, righting reflex, and grip strength. In the 5-choice serial reaction time test, adult rats showed increased numbers of anticipatory responses and omissions errors, more variable response times, and lower accuracy with evidence of delayed learning of the task demands when the 1 s stimulus duration was introduced. In contrast, prenatal nicotine exposure had no effect on exploratory locomotion or delay-discounting test. Prenatal nicotine exposure increased expression of the D5 dopamine receptor gene in the striatum, but did not change expression of other dopamine-related genes (DRD4, DAT1, NR4A2, and TH) in either the striatum or the prefrontal cortex. These data suggest a direct effect of prenatal nicotine exposure on important aspects of attention, inhibitory control, or learning later in life.
•ADHD occurs in 5.9 % of youth and 2.5 % of adults.•Most cases of ADHD are caused by the combined effects of many genetic and environmental risks.•There are small differences in the brain between ...people with and without ADHD.•Untreated ADHD can lead to many adverse outcomes.•ADHD costs society hundreds of billions of dollars each year, worldwide.
Misconceptions about ADHD stigmatize affected people, reduce credibility of providers, and prevent/delay treatment. To challenge misconceptions, we curated findings with strong evidence base.
We reviewed studies with more than 2000 participants or meta-analyses from five or more studies or 2000 or more participants. We excluded meta-analyses that did not assess publication bias, except for meta-analyses of prevalence. For network meta-analyses we required comparison adjusted funnel plots. We excluded treatment studies with waiting-list or treatment as usual controls. From this literature, we extracted evidence-based assertions about the disorder.
We generated 208 empirically supported statements about ADHD. The status of the included statements as empirically supported is approved by 80 authors from 27 countries and 6 continents. The contents of the manuscript are endorsed by 366 people who have read this document and agree with its contents.
Many findings in ADHD are supported by meta-analysis. These allow for firm statements about the nature, course, outcome causes, and treatments for disorders that are useful for reducing misconceptions and stigma.
•Excessive, spontaneous mind wandering is associated with attention deficit hyperactivity disorder (ADHD).•Deficient regulation of the default mode network in ADHD might lead to this type of mind ...wandering.•This neural dysregulation might also underpin inattention and deficient cognitive performance.•Converging evidence draws parallels between regulatory processes of mind wandering and deficient regulation in ADHD.
Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder associated with a range of mental health, neurocognitive and functional problems. Although the diagnosis is based on descriptions of behaviour, individuals with ADHD characteristically describe excessive spontaneous mind wandering (MW). MW in individuals with ADHD reflects constant mental activity which lacks topic stability and content consistency. Based on this review of the neural correlates of ADHD and MW, we outline a new perspective on ADHD: the MW hypothesis. We propose that altered deactivation of the default mode network, and dysfunctional interaction with the executive control network, leads to excessive and spontaneous MW, which underpins symptoms and impairments of ADHD. We highlight that processes linked to the normal neural regulation of MW (context regulation, sensory decoupling, salience thresholds) are deficient in ADHD. MW-related measures could serve as markers of the disease process, as MW can be experimentally manipulated, as well as measured using rating scales, and experience sampling during both cognitive tasks and daily life. MW may therefore be a potential endophenotype.
Attention deficit hyperactivity disorder (ADHD) is a common childhood disorder that frequently persists into adulthood, with significant levels of inattentive, hyperactive and impulsive behavior. ...Impairments associated with adult ADHD include distress from the symptoms, impaired ability to function in work and academic settings, and problems sustaining stable relationships. The disorder is commonly associated with volatile moods, antisocial behavior, and drug and alcohol misuse. There is an increased risk of developing comorbid anxiety, depression, personality disorders, and drug and alcohol dependence. Despite the proven effectiveness of drugs such as methylphenidate, dexamphetamine and atomoxetine, few cases of ADHD are recognized and treated in the UK. The reasons for this are unclear, since most psychiatrists working with children and adolescents are aware that ADHD commonly persists into adult life and they also see the disorder affecting parents of children with ADHD. Issues of transition from the care of child to adult psychiatry and the need to refer adult relatives of children with ADHD to suitable psychiatric services are a major concern. Furthermore, many cases of adult ADHD go unrecognized or are seen by mental health teams that are not familiar with the subtleties of the adult presentation. As a result, misdiagnosis and treatment for conditions such as atypical depression, mixed affective disorder, cyclothymia, and borderline and unstable emotional personality disorders is not uncommon. There is therefore a requirement for further training in this area. This review will describe the common clinical presentation and provide guidelines for the diagnosis and treatment of ADHD in adults. Any psychiatrically trained physician using standard psychiatric assessment procedures can perform clinical evaluations for adult ADHD. As with other psychiatric disorders in adulthood, ADHD has its own characteristic onset, course and psychopathology. Symptoms of ADHD are trait-like, being stable characteristics from early childhood, and commonly co-occur with affective instability. Stimulants are the mainstay of treatment and are effective in around 70% of cases. Psychotherapeutic interventions also have an important role. These guidelines will assist psychiatrists and other adult mental health workers in identifying and treating individuals with adult ADHD.
In youth, ADHD is more commonly diagnosed in males than females, but higher male-to-female ratios are found in clinical versus population-based samples, suggesting a sex bias in the process of ...receiving a clinical diagnosis of ADHD. This study investigated sex differences in the severity and presentation of ADHD symptoms, conduct problems, and learning problems in males and females with and without clinically diagnosed ADHD. We then investigated whether the predictive associations of these symptom domains on being diagnosed and treated for ADHD differed in males and females. Parents of 19,804 twins (50.64% male) from the Swedish population completed dimensional assessments of ADHD symptoms and co-occurring traits (conduct and learning problems) when children were aged 9 years. Children from this population sample were linked to Patient Register data on clinical ADHD diagnosis and medication prescriptions. At the population level, males had higher scores for all symptom domains (inattention, hyperactivity/impulsivity, conduct, and learning problems) compared to females, but similar severity was seen in clinically diagnosed males and females. Symptom severity for all domains increased the likelihood of receiving an ADHD diagnosis in both males and females. Prediction analyses revealed significant sex-by-symptom interactions on diagnostic and treatment status for hyperactivity/impulsivity and conduct problems. In females, these behaviours were stronger predictors of clinical diagnosis (hyperactivity/impulsivity: OR 1.08, 95% CI 1.01, 1.15; conduct: OR 1.43, 95% CI 1.09, 1.87), and prescription of pharmacological treatment (hyperactivity/impulsivity: OR 1.24, 95% CI 1.02, 1.50; conduct: OR 2.20, 95% CI 1.05, 4.63). Females with ADHD may be more easily missed in the ADHD diagnostic process and less likely to be prescribed medication unless they have prominent externalising problems.
The genetic and environmental link between attention-deficit/hyperactivity disorder in childhood and the adult manifestation of the disorder is poorly understood because of a lack of longitudinal ...studies with cross-informant data.
To explore the relative contribution of genetic and environmental influences on symptoms of attention problems from childhood to early adulthood.
Analysis was conducted using longitudinal structural equation modeling with multiple informants.
The Swedish Twin Study of Child and Adolescent Development.
One thousand four hundred eighty twin pairs were prospectively followed up from childhood to young adulthood.
Symptoms were obtained using parent and self-ratings of the Attention Problems Scale at ages 8 to 9, 13 to 14, 16 to 17, and 19 to 20 years.
The best-fitting model revealed high heritability of attention problems as indexed by parent and self-ratings from childhood to early adulthood (h² = 0.77-0.82). Genetic effects operating at age 8 to 9 years continued, explaining 41%, 34%, and 24% of the total variance at ages 13 to 14, 16 to 17, and 19 to 20 years. Moreover, new sets of genetic risk factors emerged at ages 13 to 14, 16 to 17, and 19 to 20 years.
The shared view of self- and informant-rated attention problems is highly heritable in childhood, adolescence, and early adulthood, suggesting that the previous reports of low heritability for attention-deficit/hyperactivity disorder in adults are best explained by rater effects. Both genetic stability and genetic innovation were present throughout this developmental stage, suggesting that attention problems are a developmentally complex phenotype characterized by both continuity and change across the life span.
For many years, attention-deficit hyperactivity disorder (ADHD) was thought to be a childhood-onset disorder that has a limited effect on adult psychopathology. However, the symptoms and impairments ...that define ADHD often affect the adult population, with similar responses to drugs such as methylphenidate, dexamphetamine, and atomoxetine, and psychosocial interventions, to those seen in children and adolescents. As a result, awareness of ADHD in adults has rapidly increased and new clinical practice has emerged across the world. Despite this progress, treatment of adult ADHD in Europe and many other regions of the world is not yet common practice, and diagnostic services are often unavailable or restricted to a few specialist centres. This situation is remarkable given the strong evidence base for safe and effective treatments. Here we address some of the key conceptual issues surrounding the diagnosis of ADHD relevant to practising health-care professionals working with adult populations. We conclude that ADHD should be recognised in the same way as other common adult mental health disorders, and that failure to recognise and treat ADHD is detrimental to the wellbeing of many patients seeking help for common mental health problems.
Neuroimaging studies have shown structural alterations in several brain regions in children and adults with attention deficit hyperactivity disorder (ADHD). Through the formation of the international ...ENIGMA ADHD Working Group, we aimed to address weaknesses of previous imaging studies and meta-analyses, namely inadequate sample size and methodological heterogeneity. We aimed to investigate whether there are structural differences in children and adults with ADHD compared with those without this diagnosis.
In this cross-sectional mega-analysis, we used the data from the international ENIGMA Working Group collaboration, which in the present analysis was frozen at Feb 8, 2015. Individual sites analysed structural T1-weighted MRI brain scans with harmonised protocols of individuals with ADHD compared with those who do not have this diagnosis. Our primary outcome was to assess case-control differences in subcortical structures and intracranial volume through pooling of all individual data from all cohorts in this collaboration. For this analysis, p values were significant at the false discovery rate corrected threshold of p=0·0156.
Our sample comprised 1713 participants with ADHD and 1529 controls from 23 sites with a median age of 14 years (range 4-63 years). The volumes of the accumbens (Cohen's d=-0·15), amygdala (d=-0·19), caudate (d=-0·11), hippocampus (d=-0·11), putamen (d=-0·14), and intracranial volume (d=-0·10) were smaller in individuals with ADHD compared with controls in the mega-analysis. There was no difference in volume size in the pallidum (p=0·95) and thalamus (p=0·39) between people with ADHD and controls. Exploratory lifespan modelling suggested a delay of maturation and a delay of degeneration, as effect sizes were highest in most subgroups of children (<15 years) versus adults (>21 years): in the accumbens (Cohen's d=-0·19 vs -0·10), amygdala (d=-0·18 vs -0·14), caudate (d=-0·13 vs -0·07), hippocampus (d=-0·12 vs -0·06), putamen (d=-0·18 vs -0·08), and intracranial volume (d=-0·14 vs 0·01). There was no difference between children and adults for the pallidum (p=0·79) or thalamus (p=0·89). Case-control differences in adults were non-significant (all p>0·03). Psychostimulant medication use (all p>0·15) or symptom scores (all p>0·02) did not influence results, nor did the presence of comorbid psychiatric disorders (all p>0·5).
With the largest dataset to date, we add new knowledge about bilateral amygdala, accumbens, and hippocampus reductions in ADHD. We extend the brain maturation delay theory for ADHD to include subcortical structures and refute medication effects on brain volume suggested by earlier meta-analyses. Lifespan analyses suggest that, in the absence of well powered longitudinal studies, the ENIGMA cross-sectional sample across six decades of ages provides a means to generate hypotheses about lifespan trajectories in brain phenotypes.
National Institutes of Health.
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