Version May 2024
INTRODUCTION — Attention deficit hyperactivity disorder (ADHD) is a disorder that manifests in childhood with symptoms of hyperactivity, impulsivity, and/or inattention. The symptoms affect cognitive, academic, behavioral, emotional, and social functioning [1].
This topic review focuses on the epidemiology and pathogenesis of ADHD. The evaluation, diagnosis, management, and prognosis of ADHD in children and ADHD in adults are discussed separately.
DEFINITION — ADHD is a disorder that manifests in early childhood with symptoms of hyperactivity, impulsivity, and/or inattention. The symptoms affect cognitive, academic, behavioral, emotional, and social functioning [1]. (See "Attention deficit hyperactivity disorder in children and adolescents: Clinical features and diagnosis", section on 'Clinical features' and "Attention deficit hyperactivity disorder in children and adolescents: Clinical features and diagnosis", section on 'Core symptoms'.)
EPIDEMIOLOGY
Prevalence — The reported prevalence of ADHD in children varies from 2 to 18 percent depending upon the diagnostic criteria and the population studied (eg, primary care versus referral) [1-5]. The prevalence in school-age children is estimated to be between 9 and 15 percent, making it one of the most common disorders of childhood [3,5-10]. In a meta-analysis of 175 studies (including 1,023,071 subjects over 36 years), the estimated pooled prevalence of ADHD was 7.2 percent (95% CI 6.7 to 7.8) [11]. The studies were from a broad geographic distribution (eg, Europe, Asia, North America). Most were conducted in school-age children.
In the 2015 to 2016 National Health Interview Survey (NHIS), the weighted prevalence of a caregiver-reported diagnosis of ADHD among children aged 4 to 17 years of age in the United States was 10 percent [12]. This is an increase from 6 percent in 1997 to 1998. The prevalence increased with increasing age (7.7 percent among 4- to 11-year-olds and 13.5 percent among 12- to 17-year-olds).
ADHD is more common in males than females (male to female ratio 4:1 for the predominantly hyperactive presentation and 2:1 for the predominantly inattentive presentation) [13]. In the 2015 to 2016 NHIS, the prevalence was 14 percent in males and 6 percent in females [12].
ADHD is not a reportable disease. The primary sources of information regarding prevalence are parent report and extrapolation from medical records, billing, or pharmacy records – each of which has limitations. Potential explanations for the apparent increase in prevalence of ADHD over time include improved awareness and case-identification by primary care professionals, educators, and parents or more frequent exposure to some of the potential etiologic factors discussed below. (See 'Pathogenesis: Potential environmental influences' below.)
Comorbid disorders — Children and adolescents with ADHD frequently have comorbid psychiatric and neurodevelopmental disorders, including (but not limited to) oppositional defiant disorder (ODD), conduct disorder, depression, anxiety disorder, autism spectrum disorder (ASD), and learning disorders [14-20]. The comorbid conditions can be primary or secondary (eg, exacerbated by the ADHD). In either case, they require treatment independent of, but often in addition to, the treatment for ADHD [5,21,22]. (See "Attention deficit hyperactivity disorder in children and adolescents: Clinical features and diagnosis", section on 'Evaluation for coexisting disorders'.)
●Oppositional defiant disorder – ODD coexists with ADHD in approximately 50 to 80 percent of cases [13,19,23]. It is more common in children with the combined and hyperactive-impulsive presentations [24,25]. Their excessive activity, impulsive response style, and disinhibited emotional expression frequently put them in conflict with caregivers and other adults. The increased conflict may lead to increased discipline and less positive reinforcement for the child. Under these circumstances, a potentially self-perpetuating pattern of oppositional defiant behavior can emerge (the oppositional acts bring parental attention, which is reinforcing for the child who rarely receives parental praise) [26-28]. (See "Oppositional defiant disorder: Epidemiology, clinical manifestations, course, and diagnosis".)
●Conduct disorder – Conduct disorder coexists with ADHD in as many as one-third of cases [13,14,19]. Like ODD, it is more common in the combined and hyperactive-impulsive presentations [24,25].
●Anxiety disorder – Anxiety disorder coexists with ADHD in approximately 20 to 40 percent of cases [13,14,19,23]. It occurs more frequently in the inattentive presentation [13,24,25]. Anxiety may develop as a secondary disorder in children with ADHD; however, in many cases, anxiety appears to be a distinct disorder and may be independent of ADHD [15,29]. (See "Anxiety disorders in children and adolescents: Epidemiology, pathogenesis, clinical manifestations, and course" and "Pharmacotherapy for anxiety disorders in children and adolescents".)
●Depression – Depression coexists with ADHD in as many as one-third of cases [13,14,19,23]. It appears be more common in the inattentive and combined presentations [24,25]. Children with ADHD and comorbid mood disorder may have family members with a history of major depressive disorder [17]. Adolescents with ADHD and mood disorder are at increased risk for attempting suicide [30-32]. (See "Pediatric unipolar depression: Epidemiology, clinical features, assessment, and diagnosis" and "Suicidal behavior in children and adolescents: Epidemiology and risk factors".)
●Learning disorder – Estimates for the coexistence of learning disorders and ADHD range from 20 to 60 percent [13,14,18,26,33]. In a population-based birth cohort, approximately 40 percent of children with ADHD also had reading disability, and approximately 60 percent of children with ADHD also had written-language disorder [33,34]. Learning disorders appear to occur more commonly among children with the inattentive and combined presentations of ADHD [24,25]. (See "Specific learning disorders in children: Clinical features", section on 'Comorbidities'.)
Data regarding the rates of coexistence of specific types of learning disorders and ADHD are lacking. In a study of 445 ninth-grade students, children with reading disabilities were twice as likely to meet diagnostic criteria for the inattentive presentation than the general population (15 versus 7 percent) [35]. Conversely, individuals with ADHD were at higher risk than the general population for reading disability or phonologic awareness deficit (36 versus 17 percent). (See "Reading difficulty in children: Normal reading development and etiology of reading difficulty" and "Reading difficulty in children: Clinical features and evaluation".)
●Developmental coordination disorder – Approximately one-half of children with ADHD meet criteria for developmental coordination disorder (DCD). The association between ADHD and DCD is discussed separately. (See "Developmental coordination disorder: Clinical features and diagnosis", section on 'Evaluation for associated conditions'.)
●Autism spectrum disorder – ASD often coexists with ADHD, though many children with ADHD do not have ASD [36,37]. In children with comorbid ADHD and ASD, initial diagnosis of ADHD may delay diagnosis of ASD [38]. Children with comorbid ADHD and ASD usually have more severe cognitive impairment, behavior problems, and psychopathology than children with isolated ADHD or ASD [39-42]. (See "Autism spectrum disorder in children and adolescents: Clinical features" and "Autism spectrum disorder in children and adolescents: Evaluation and diagnosis".)
●Sleep disorders – Children with ADHD may have comorbid sleep disorders [5]. In addition, sleep disturbances underlie behavioral symptoms. The association between sleep disturbances and ADHD is discussed separately. (See "Evaluation of suspected obstructive sleep apnea in children", section on 'Daytime symptoms' and "Cognitive and behavioral consequences of sleep disorders in children", section on 'Clinical consequences of sleep deficiency' and "Attention deficit hyperactivity disorder in children and adolescents: Clinical features and diagnosis", section on 'Differential diagnosis'.)
PATHOGENESIS: PRIMARY FACTORS — The pathogenesis of ADHD is not definitively known. A genetic imbalance of catecholamine metabolism in the cerebral cortex appears to play a primary role, as illustrated by structural and functional brain imaging, animal studies, and the response to drugs with noradrenergic activity (eg, methylphenidate) [23,43,44]. However, various environmental factors may play a secondary role; the significance of environmental factors is controversial. (See 'Pathogenesis: Potential environmental influences' below.)
Genetic factors — A genetic contribution to the pathogenesis of ADHD is supported by the increased risk of ADHD in first-degree relatives of patients with ADHD and twin studies from different countries that consistently provide heritability estimates of approximately 75 percent [45-48]. Although genetic variants associated with ADHD have been identified (eg, single nucleotide polymorphisms, copy number variants), the identified genetic variants are not specific for ADHD [46,49]. (See "Genomic disorders: An overview", section on 'Copy number variations' and "Basic genetics concepts: DNA regulation and gene expression", section on 'Genetic variation'.)
Neuroanatomy
●Structural and functional differences – Structural brain imaging in groups of children with and without ADHD demonstrates significant differences in many areas [50]. In observational studies, children with ADHD have reversed or absent asymmetry of the caudate nucleus, smaller cerebral and cerebellar volume, smaller posterior corpus callosum regions, and increased gray matter in the posterior temporal and inferior parietal cortices compared with children without ADHD [51-54]. Differences are particularly noted in anterior brain areas, including smaller prefrontal cortical volumes and reduced thickness of the anterior cingulate cortex, as well as cortical thinning in bilateral superior frontal brain regions [55-58].
Functional brain imaging reveals that groups of children with ADHD have reduced global activation and reduced local activation in the areas of the basal ganglia and anterior frontal lobe [59-65]. The administration of methylphenidate affects activation in these and other areas. However, the effect varies depending upon the area, with age, and whether the child has ADHD [66,67]. These findings support the hypothesis that ADHD is characterized by atypical frontal-striatal function and that methylphenidate affects striatal activation differently in ADHD than in healthy children.
●Clinical correlation – Neuropsychologic testing suggests that patients with ADHD have impaired executive functions (processes involved in forward planning, including abstract reasoning, mental flexibility, working memory) and/or difficulties with response inhibition [68,69]. These findings are consistent with neuroimaging studies that demonstrate structural and functional abnormalities in prefrontal structures and basal ganglia regions (which underlie motor response inhibition and executive functions) [70-72].
Catecholamine metabolism — Catecholamines include dopamine and epinephrine. Catecholamine metabolism appears to play a role in ADHD pathogenesis [46,73]. In animal studies, the noradrenergic system is involved in the modulation of higher cortical functions, including attention, alertness, vigilance, and executive function [74]. Rat models suggest that an imbalance between the norepinephrine and dopamine systems in the prefrontal cortex contributes to the pathogenesis of ADHD (decrease in inhibitory dopaminergic activity and increase in norepinephrine activity) [75].
The findings from animal studies are supported by human studies indicating patients with ADHD have an increase in dopamine transporter density (which may clear dopamine from the synapse too quickly) compared with healthy controls [76] and that methylphenidate increases extracellular dopamine in the brain [77].
PATHOGENESIS: POTENTIAL ENVIRONMENTAL INFLUENCES — Various environmental factors may play a secondary role in the pathogenesis of ADHD [43,44,78]. The significance of environmental factors is controversial.
When considering the contribution of environmental factors, it is important to distinguish between the behavioral symptoms of ADHD and the clinical syndrome of ADHD. Inattentiveness, impulsivity, and hyperactivity occur to some extent in all children. It is the persistence, pervasiveness, developmental inappropriateness, and functional complications of the behavioral symptoms that lead to a diagnosis of ADHD. To meet criteria for ADHD, symptoms must [1]:
●Be present in more than one setting (eg, school and home)
●Persist for at least six months
●Be present before the age of 12 years
●Impair function in academic, social, or occupational activities
●Be excessive for the developmental level of the child
●Not be caused by other mental disorders
The clinical features and diagnosis of ADHD are discussed separately. (See "Attention deficit hyperactivity disorder in children and adolescents: Clinical features and diagnosis", section on 'Diagnostic criteria' and "Attention deficit hyperactivity disorder in children and adolescents: Clinical features and diagnosis".)
Dietary influences — The influence of diet on attention, hyperactivity, and behavior is controversial. The evidence relating diet to ADHD symptoms is limited; it consists predominantly of observational studies based on caregiver reports.
Areas of investigation include:
●Food additives (artificial colors, artificial flavors, preservatives)
●Refined sugar intake
●Food sensitivity (allergy or intolerance)
●Various fatty acid deficiencies
●Iron and zinc deficiency
These dietary factors generally do not impact behavior to a clinically significant level and do not account for the majority of cases of ADHD [43,79]. However, a small subset of children may demonstrate mild adverse behavior or inattention on diets containing food additives, artificial colors, excess sugar, or reduced intake of essential fatty acids and minerals. Similarly, food sensitivity may be associated with behavioral abnormalities, but only infrequently with the clinical syndrome of ADHD. (See "Attention deficit hyperactivity disorder in children and adolescents: Clinical features and diagnosis", section on 'Diagnostic criteria'.)
The implications of these findings on the management of children with ADHD are discussed separately. (See "Attention deficit hyperactivity disorder in children and adolescents: Overview of treatment and prognosis", section on 'Dietary interventions'.)
●Food additives – The effect of food additives (artificial colors and flavors, preservatives) on the behavior of children is an active area of investigation. Although some studies support a relationship between food additives and ADHD symptoms in some children, they do not prove that food additives cause ADHD. Major practice guidelines for the treatment of ADHD and for food allergy management do not routinely recommend elimination of food additives in the management of children with ADHD [5,23,44,80,81]. (See "Attention deficit hyperactivity disorder in children and adolescents: Overview of treatment and prognosis", section on 'Elimination diets'.)
The body of literature focusing on the behavioral effects of food additives suggests that some children (both with and without ADHD) may have identifiable sensitivity to specific additives [82-87]. However, this conclusion is not universally accepted, and the issue remains controversial. In March 2011, the Food Advisory Committee of the US Food and Drug Administration determined that existing data do not support a causal link between consumption of color additives and hyperactivity or other problematic behaviors in children [88].
Food additives were first suggested as a potential cause of hyperactive behavior in the 1970s [89]. Studies that followed yielded mixed results. In a 2012 meta-analysis of five randomized crossover studies, restriction diets reduced ADHD symptoms in children (effect size 0.29, 95% CI 0.16-0.52) [85]. Masked challenge with specific food colors had a small effect on caregiver-reported ADHD symptoms (20 studies, 794 participants, effect size 0.18, 95% CI 0.08-0.29), and a non-significant effect on teacher-reported symptoms (10 studies, 323 participants effect size 0.07, 95% CI -0.03-0.18). This discrepancy between parent and health professional/teacher report of symptoms has been noted in other studies [82,90].
●Refined sugar – Adverse behavior effects, including hyperactivity, are commonly attributed to excess sugar intake by parents and teachers [91,92]. There are two proposed mechanisms: sensitivity to refined sugar and functional reactive hypoglycemia (which triggers release of stress hormones such as adrenaline) after ingesting sugar [83,93].
A meta-analysis of 23 studies in which sugar was eliminated from the diet and/or children were challenged with sugar failed to support an association between sugar intake and hyperactivity, attention span, or cognitive functioning [94]. However, a small effect of sugar on subsets of children could not be excluded. A 2005 systematic review that included a slightly different set of trials supported the conclusion of the earlier meta-analysis but points out that most of the trials used relatively low-sugar challenges (equivalent to roughly one 16 ounce bottle of soda) [83].
●Unhealthy eating patterns – Unhealthy eating patterns include consumption of food additives, refined sugars, saturated fat, and processed/ultraprocessed foods, combining several independent dietary influences. A meta-analyses of observational studies found weak evidence that unhealthy eating patterns were associated with increased risk of ADHD [95]. In contrast, healthy eating patterns (eg, plant-based with little consumption of food additives, refined sugars, saturated fat, and processed/ultraprocessed foods) were associated with decreased risk of ADHD.
●Food sensitivity – For most children, food sensitivity does not appear to contribute to the pathogenesis of ADHD. There are few well-designed trials evaluating the potential association between food sensitivity (allergy or intolerance) and behavior. Demonstration of such an association requires removal of the suspect food(s) from the child's diet (elimination diet) followed by challenge with the suspect food(s) versus placebo [83].
The oligoallergenic diet (OAD) is an example of an elimination diet that may be used to assess the relationship between food sensitivity and behavior. The OAD restricts intake to a few foods that are unlikely to cause allergy (eg, turkey, lamb, rice, potato, banana, apple, pear, a few vegetables, water, salt and pepper) [83]. Although parents and teachers must supervise the elimination diet, which precludes blinding during this stage, they can be blinded when the child is challenged with the suspect food(s).
A review of double-blind placebo-controlled trials of the OAD in children with ADHD [96-99] found that behavior improved during the elimination phase [83]. However, behavior also improved during the placebo phases of the food challenge [96-98], or when the OAD diet was compared with a placebo diet (common foods with similar appearance to foods included in the OAD) [99]. The authors of the review concluded that some children may have identifiable sensitivities to certain foods. Nonetheless, food sensitivity plays no role in the majority of cases of ADHD.
A subsequent randomized trial determined that the identification of foods that may be associated with ADHD symptoms cannot be achieved by measuring immunoglobulin G levels, a common practice in complementary medicine [100,101].
●Fatty acid deficiency – Long-chain polyunsaturated fatty acids (LCPUFA) include the n-3 (or omega-3) fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) and the n-6 (or omega-6) fatty acid, arachidonic acid. LCPUFA are necessary for the development and functioning of neuronal membranes.
Some studies have noted decreased concentrations of various fatty acids (eg, free fatty acids, n-3 LCPUFA) in the serum of children with ADHD and/or lower ratios of n-3 LCPUFA to n-6 LCPUFA, suggesting that deficiency of certain fatty acids may play a role in the pathogenesis of ADHD [102-106]. However, evidence that fatty acid supplementation improves ADHD symptoms is limited, and the role of fatty acid supplementation in the pathogenesis of ADHD remains unclear [87,107-110]. (See "Attention deficit hyperactivity disorder in children and adolescents: Overview of treatment and prognosis", section on 'Essential fatty acid supplementation'.)
●Iron deficiency – The role of iron deficiency in ADHD has not been clearly defined. However, low serum ferritin has been associated with cognitive and learning disorders, and iron deficiency has been associated with abnormal dopaminergic neurotransmission (iron is a co-enzyme of dopamine synthesis) [111,112]. In addition, there appears to be an overlap between restless leg syndrome (which is associated with iron deficiency) and ADHD symptoms in children [113,114]. (See "Restless legs syndrome and periodic limb movement disorder in children", section on 'Iron deficiency'.)
Case-control studies of ferritin levels in children with ADHD have had inconsistent results [112,115-118]. Additional studies are necessary to confirm or refute an association between iron deficiency and ADHD [43].
●Zinc deficiency – Several controlled studies demonstrating zinc deficiency or a beneficial response to zinc supplementation in children with ADHD suggest that zinc deficiency may play a role in the pathogenesis of ADHD [119,120]. However, a systematic review of three randomized trials did not find a beneficial effect of zinc on ADHD symptoms [121]. Additional studies are necessary to confirm this hypothesis [43,120].
Sleep deficiency — Insufficient sleep may exacerbate symptoms of ADHD. Behavioral consequences of sleep deficiency are discussed separately. (See "Cognitive and behavioral consequences of sleep disorders in children", section on 'Clinical consequences of sleep deficiency'.)
Prenatal medications — The unproven associations between ADHD and prenatal exposure to antidepressants and acetaminophen are discussed separately. (See "Antenatal exposure to selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs): Risk of psychopathology in the offspring", section on 'Attention deficit hyperactivity disorder' and "Prenatal care: Patient education, health promotion, and safety of commonly used drugs", section on 'Acetaminophen'.)
Prenatal exposure to tobacco smoke — Prenatal exposure to tobacco smoke is consistently associated with development of ADHD in case-control and cohort studies [122,123]. It is uncertain whether this association is causal or mediated by unmeasured environmental or genetic confounders [124-126]. (See "Cigarette and tobacco products in pregnancy: Impact on pregnancy and the neonate", section on 'Long-term effects'.)
Prematurity — Observational studies and meta-analysis of observational studies also suggest that prematurity and low birth weight are associated with ADHD, although it uncertain whether this association is causal. (See "Long-term neurodevelopmental impairment in infants born preterm: Epidemiology and risk factors".)
Other factors — Other factors that have been associated with the development of ADHD, but in which the association is inconsistent, include [43,78]:
●Prenatal exposure to alcohol [127-131] (see "Fetal alcohol spectrum disorder: Clinical features and diagnosis", section on 'Central nervous system involvement')
●Head trauma in young children [132] (see "Minor head trauma in infants and children: Management", section on 'Complications')
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Attention deficit hyperactivity disorder".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword[s] of interest.)
●Basics topics (see "Patient education: Attention deficit hyperactivity disorder (ADHD) in children (The Basics)")
●Beyond the Basics topics (see "Patient education: Symptoms and diagnosis of attention deficit hyperactivity disorder in children (Beyond the Basics)")
SUMMARY
●Definition – Attention deficit hyperactivity disorder (ADHD) is a disorder that manifests in early childhood with symptoms of hyperactivity, impulsivity, and/or inattention. (See 'Definition' above.)
●Prevalence – The prevalence of ADHD is estimated to be between 8 and 10 percent in school-age children; it is more common in males than females. (See 'Prevalence' above.)
●Comorbid disorders – Children and adolescents with ADHD frequently have comorbid disorders, including oppositional defiant disorder, conduct disorder, depression, anxiety disorder, learning disorders, developmental coordination disorder, autism spectrum disorder, and sleep disorders. Sleep deficiency may be an exacerbating factor. (See 'Comorbid disorders' above and 'Sleep deficiency' above.)
●Pathogenesis – The pathogenesis of ADHD is not definitively known. A genetic imbalance of catecholamine metabolism in the cerebral cortex appears to play a primary role. (See 'Pathogenesis: Primary factors' above.)
Various environmental factors may play a secondary role in the pathogenesis of ADHD; the significance of environmental factors is controversial. (See 'Pathogenesis: Potential environmental influences' above.)
Dietary factors (food additives, sugar, food sensitivity, essential fatty acid deficiency, mineral deficiency) generally do not impact behavior to a clinically significant level and do not account for the majority of cases of ADHD. However, a small subset of children may demonstrate mild adverse behavioral effects in response to dietary influences. (See 'Dietary influences' above.)
Prenatal exposure to tobacco and prematurity/low birth weight are associated with development of ADHD. Other factors that have been associated with the development of ADHD, but in which the association is inconsistent, include prenatal exposure to alcohol and head trauma. (See 'Other factors' above.)
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