research studies for adhd

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

• Advanced Search
• Journal List
• Thieme Open Access

ADHD: Current Concepts and Treatments in Children and Adolescents

Renate drechsler.

1 Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry, University of Zurich, Zurich, Switzerland

Silvia Brem

2 Neuroscience Center Zurich, Swiss Federal Institute of Technology and University of Zurich, Zurich, Switzerland

Daniel Brandeis

3 Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany

4 Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland

Edna Grünblatt

Gregor berger, susanne walitza.

Attention deficit hyperactivity disorder (ADHD) is among the most frequent disorders within child and adolescent psychiatry, with a prevalence of over 5%. Nosological systems, such as the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) and the International Classification of Diseases, editions 10 and 11 (ICD-10/11) continue to define ADHD according to behavioral criteria, based on observation and on informant reports. Despite an overwhelming body of research on ADHD over the last 10 to 20 years, valid neurobiological markers or other objective criteria that may lead to unequivocal diagnostic classification are still lacking. On the contrary, the concept of ADHD seems to have become broader and more heterogeneous. Thus, the diagnosis and treatment of ADHD are still challenging for clinicians, necessitating increased reliance on their expertise and experience. The first part of this review presents an overview of the current definitions of the disorder (DSM-5, ICD-10/11). Furthermore, it discusses more controversial aspects of the construct of ADHD, including the dimensional versus categorical approach, alternative ADHD constructs, and aspects pertaining to epidemiology and prevalence. The second part focuses on comorbidities, on the difficulty of distinguishing between “primary” and “secondary” ADHD for purposes of differential diagnosis, and on clinical diagnostic procedures. In the third and most prominent part, an overview of current neurobiological concepts of ADHD is given, including neuropsychological and neurophysiological researches and summaries of current neuroimaging and genetic studies. Finally, treatment options are reviewed, including a discussion of multimodal, pharmacological, and nonpharmacological interventions and their evidence base.

Introduction

With a prevalence of over 5%, attention deficit hyperactivity disorder (ADHD) is one of the most frequent disorders within child and adolescent psychiatry. Despite an overwhelming body of research, approximately 20,000 publications have been referenced in PubMed during the past 10 years, assessment and treatment continue to present a challenge for clinicians. ADHD is characterized by the heterogeneity of presentations, which may take opposite forms, by frequent and variable comorbidities and an overlap with other disorders, and by the context-dependency of symptoms, which may or may not become apparent during clinical examination. While the neurobiological and genetic underpinnings of the disorder are beyond dispute, biomarkers or other objective criteria, which could lead to an automatic algorithm for the reliable identification of ADHD in an individual within clinical practice, are still lacking. In contrast to what one might expect after years of intense research, ADHD criteria defined by nosological systems, such as the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) and the International Classification of Diseases, editions 10 and 11 (ICD-10/11) have not become narrower and more specific. Rather, they have become broader, for example, encompassing wider age ranges, thus placing more emphasis on the specialist's expertise and experience. 1 2 3

Definitions and Phenomenology

Adhd according to the dsm-5 and icd-10/11.

ADHD is defined as a neurodevelopmental disorder. Its diagnostic classification is based on the observation of behavioral symptoms. ADHD according to the DSM-5 continues to be a diagnosis of exclusion and should not be diagnosed if the behavioral symptoms can be better explained by other mental disorders (e.g., psychotic disorder, mood or anxiety disorder, personality disorder, substance intoxication, or withdrawal). 1 However, comorbidity with other mental disorders is common.

In the DSM-5, the defining symptoms of ADHD are divided into symptoms of inattention (11 symptoms) and hyperactivity/impulsivity (9 symptoms). 1 The former differentiation between subtypes in the DSM-IV proved to be unstable and to depend on the situational context, on informants, or on maturation, and was therefore replaced by “presentations.” 4 Thus, the DSM-5 distinguishes between different presentations of ADHD: predominantly inattentive (6 or more out of 11 symptoms present), predominantly hyperactive/impulsive (6 or more out of 9 symptoms present), and combined presentation (both criteria fulfilled), as well as a partial remission category. Symptoms have to be present in two or more settings before the age of 12 years for at least 6 months and have to reduce or impair social, academic, or occupational functioning. In adolescents over 17 years and in adults, five symptoms per dimension need to be present for diagnosis. 1 In adults, the use of validated instruments like the Wender Utah rating scale is recommended. 5

In contrast, the ICD-10 classification distinguishes between hyperkinetic disorder of childhood (with at least six symptoms of inattention and six symptoms of hyperactivity/impulsivity, present before the age of 6 years) and hyperkinetic conduct disorder, a combination of ADHD symptoms and symptoms of oppositional defiant and conduct disorders (CD). 3 In the ICD-11 (online release from June 2018, printed release expected 2022), the latter category has been dropped, as has the precise age limit (“onset during the developmental period, typically early to mid-childhood”). Moreover, the ICD-11 distinguishes five ADHD subcategories, which match those of the DSM-5: ADHD combined presentation, ADHD predominantly inattentive presentation, ADHD predominantly hyperactive/impulsive presentation and two residual categories, ADHD other specified and ADHD nonspecified presentation. For diagnosis, behavioral symptoms need to be outside the limits of normal variation expected for the individual's age and level of intellectual functioning. 2

Overlapping Constructs: Sluggish Cognitive Tempo and Emotional Dysregulation

Sluggish cognitive tempo (SCT) is a clinical construct characterized by low energy, sleepiness, and absent-mindedness, and is estimated to occur in 39 to 59% of (adult) individuals with ADHD. 6 7 The question of whether SCT might constitute a feature of ADHD or a separate construct that overlaps with ADHD inattention symptoms is unresolved. 8 While current studies indicate that SCT might be distinct and independent from hyperactivity/impulsivity, as well as from inattention dimensions, it remains uncertain whether it should be considered as a separate disorder. 8 9 Twin studies have revealed a certain overlap between SCT and ADHD, especially with regard to inattention symptoms, but SCT seems to be more strongly related to nonshared environmental factors. 10

Emotion dysregulation is another associated feature that has been discussed as a possible core component of childhood ADHD, although it is not included in the DSM-5 criteria. Deficient emotion regulation is more typically part of the symptom definition of other psychopathological disorders, such as oppositional defiant disorder (ODD), CD, or disruptive mood dysregulation disorder (DSM-5; for children up to 8 years). 11 However, an estimated 50 to 75% of children with ADHD also present symptoms of emotion dysregulation, for example, anger, irritability, low tolerance for frustration, and outbursts, or sometimes express inappropriate positive emotions. The presence of these symptoms increases the risk for further comorbidities, such as ODD and also for anxiety disorders. 12 13 For adult ADHD, emotional irritability is a defining symptom according to the Wender Utah criteria, and has been confirmed as a primary ADHD symptom by several studies (e.g., Hirsch et al). 5 14 15

Whether emotion dysregulation is inherent to ADHD, applies to a subgroup with combined symptoms and a singular neurobiological pathway, or is comorbid with but independent of ADHD, is still a matter of debate (for a description of these three models; Shaw et al 13 ). Faraone et al 12 distinguished three ADHD prototypes with regard to deficient emotion regulation: ADHD prototype 1 with high-emotional impulsivity and deficient self-regulation, prototype 2 with low-emotional impulsivity and deficient self-regulation, and prototype 3 with high-emotional impulsivity and effective self-regulation. All three prototypes are characterized by an inappropriate intensity of emotional response. While prototypes 1 and 3 build up their responses very quickly, prototype 2 is slower to respond but experiences higher subjective emotional upheaval than is overtly shown in the behavior. Prototypes 1 and 2 both need more time to calm down compared with prototype 3 in which emotional self-regulation capacities are intact.

Dimensional versus Categorical Nature of ADHD

Recent research on subthreshold ADHD argues in favor of a dimensional rather than categorical understanding of the ADHD construct, as its core symptoms and comorbid features are dimensionally distributed in the population. 16 17 18 Subthreshold ADHD is common in the population, with an estimated prevalence of approximately 10%. 19 According to Biederman and colleagues, clinically referred children with subthreshold ADHD symptoms show a similar amount of functional deficits and comorbid symptoms to those with full ADHD, but tend to come from higher social-class families with fewer family conflicts, to have fewer perinatal complications, and to be older and female (for the latter two, a confound with DSM-IV criteria cannot be excluded). 20

Temperament and Personality Approaches to ADHD

Another approach which is in accordance with a dimensional concept is to analyze ADHD and categorize subtypes according to temperament/personality traits (for a review and the different concepts of temperament see Gomez and Corr 21 ). Temperament/personality traits are usually defined as neurobiologically based constitutional tendencies, which determine how the individual searches for or reacts to external stimulation and regulates emotion and activity. While temperament traits per se are not pathological, extreme variations or specific combinations of traits may lead to pathological behavior. This approach has been investigated in several studies by Martel and colleagues and Nigg, 22 23 24 who employed a temperament model comprising three empirically derived domains 25 26 : (1) negative affect, such as tendencies to react with anger, frustration, or fear; (2) positive affect or surgency which includes overall activity, expression of happiness, and interest in novelty; and (3) effortful control which is related to self-regulation and the control of action. The latter domain shows a strong overlap with the concept of executive function. 27 In a community sample, early temperamental traits, especially effortful control and activity level, were found to potentially predict later ADHD. 28 Karalunas et al 29 30 distinguished three temperament profiles in a sample of children with ADHD: one with normal emotional functioning; one with high surgency, characterized by high levels of positive approach-motivated behaviors and a high–activity level; and one with high negative (“irritable”) affect, with the latter showing the strongest, albeit only moderate stability over 2 years. Irritability was not reducible to comorbidity with ODD or CD and was interpreted as an ADHD subgroup characteristic with predictive validity for an unfavorable outcome. These ADHD temperament types were distinguished by resting-state and peripheral physiological characteristics as measured by functional magnetic resonance imaging (fMRI). 29

Epidemiology and Prevalence

While ADHD seems to be a phenomenon that is encountered worldwide, 31 prevalence rates and reported changes in prevalence are highly variable, depending on country and regions, method, and sample. 32 A meta-analysis by Polanczyk et al 32 yielded a worldwide prevalence rate of 5.8% in children and adolescents. 33 In an update published 6 years later, the authors did not find evidence for an increase in prevalence over a time span of 30 years. Other meta-analyses reported slightly higher (e.g., 7.2%) 34 or lower prevalence rates, which seems to be attributable to the different criteria adopted for defining ADHD. Prevalence rates in children and adolescents represent averaged values across the full age range, but peak prevalence may be much higher in certain age groups, for example, 13% in 9-year-old boys. 35 Universal ADHD prevalence in adults is estimated to lie at 2.8%, with higher rates in high-income (3.6%) than in low-income (1.4%) countries. 36 True prevalence rates (also called community prevalence, e.g., Sayal et al 37 ) should be based on population-based representative health surveys, that is, the actual base rate of ADHD in the population, in contrast to the administrative base rate, which is related to clinical data collection (Taylor 38 ). Recent reports on the increase in ADHD rates usually refer to administrative rates, drawn from health insurance companies, from the number of clinical referrals for ADHD, 39 clinical case identification estimates, or from the percentage of children taking stimulant medication (prescription data). Changes in these rates may be influenced by increased awareness, destigmatization, modifications in the defining criteria of ADHD, or altered medical practice. According to a recent U.S. health survey on children and adolescents (4–17 years), in which parents had to indicate whether their child had ever been diagnosed with ADHD, the percentage of diagnoses increased from 6.1% in 1997 to 10.2% in 2016. 40 A representative Danish survey based on health registry, data collected from 1995 to 2010 reported that ADHD incidence rates increased by a factor of approximately 12 (for individuals aged 4–65 years) during this period. Moreover, the gender ratio decreased from 7.5:1 to 3:1 at early school age and from 8.1:1 to 1.6:1 in adolescents in the same time frame, 41 42 probably indicating an improved awareness of ADHD symptoms in girls. In other countries, it is assumed that girls are still underdiagnosed. 38

Population register data show that the use of stimulants for ADHD has increased considerably worldwide. 43 In most countries, an increase in stimulant medication use has been observed in children since the 1990s (e.g., United Kingdom from 0.15% in 1992 to 5.1% in 2012/2013), 44 45 but in some European countries, stimulant prescription rates for children and adolescents have remained stable or decreased over the last 5 to 10 years (e.g., Germany). 35 In the United States, the prescription of methylphenidate peaked in 2012 and has since been slightly decreasing, while the use of amphetamines continues to rise. 46

Comorbidity, Differential Diagnosis, and Clinical Assessment

Comorbidity.

ADHD is characterized by frequent comorbidity and overlap with other neurodevelopmental and mental disorders of childhood and adolescence. The most frequent comorbidities are learning disorders (reading disorders: 15–50%, 4 dyscalculia: 5–30%, 47 autism spectrum disorder, which since the DSM-5 is no longer viewed as an exclusion criterion for ADHD diagnosis: 70–85%, 48 49 tic/Tourette's disorder and obsessive compulsive disorder: 20%, and 5%, 50 developmental coordination disorder: 30–50%, 51 depression and anxiety disorders: 0–45%, 52 53 and ODD and CD: 27–55% 54 ). ADHD increases the risk of substance misuse disorders 1.5-fold (2.4-fold for smoking) and problematic media use 9.3-fold in adolescence 55 56 and increases the risk of becoming obese 1.23-fold for adolescent girls. 57 58 59 It is also associated with different forms of dysregulated eating in children and adolescents. Enuresis occurs in approximately 17% of children with ADHD, 60 and sleep disorders in 25 to 70%. 61 Frequent neurological comorbidities of ADHD include migraine (about thrice more frequent in ADHD than in typically developing [TD] children) 62 63 64 and epilepsy (2.3 to thrice more frequent in ADHD than in TD children). 65 66 The risk of coexisting ADHD being seen as a comorbid condition and not the primary diagnosis is considerably enhanced in many childhood disorders of different origins. For example, the rate of comorbid ADHD is estimated at 15 to 40% 67 68 in children with reading disorders and at 26 to 41% 69 70 in children with mild intellectual dysfunction. While comorbidity in neurodevelopmental disorders may arise from a certain genetic overlap (see details under genetic associations), ADHD symptoms are also present in several disorders with well-known and circumscribed genetic defects, normally not related to ADHD (e.g., neurofibromatosis, Turner's syndrome, and Noonan's syndrome) 71 or disorders with nongenetic causes, such as traumatic brain injuries, pre-, peri- or postnatal stroke, or syndromes due to toxic agents, such as fetal alcohol syndrome. Comorbid ADHD is estimated in 20 to 50% of children with epilepsy, 72 73 in 43% of children with fetal alcohol syndrome, 74 and in 40% of children with neurofibromatosis I. 75 ADHD is three times more frequent in preterm-born children than in children born at term and four times more frequent in extremely preterm-born children. 76

Differential Diagnosis, Primary and Secondary ADHD

A range of medical and psychiatric conditions show symptoms that are also present in primary ADHD. The most important medical conditions which are known to “mimic” ADHD and need to be excluded during the diagnostic process are epilepsy (especially absence epilepsy and rolandic epilepsy), thyroid disorders, sleep disorder, drug interaction, anemia, and leukodystrophy. 77 78 The most important psychiatric conditions to be excluded are learning disorder, anxiety disorders, and affective disorders, while an adverse home environment also needs to be excluded.

However, the picture is complex, as many differential diagnoses may also occur as comorbidities. For instance, bipolar disorder, which is frequently diagnosed in children and adolescents in the United States but not in Europe, is considered as a differential diagnosis to ADHD, but ADHD has also been found to be a comorbidity of bipolar disorder in 21 to 98% of cases. 79 Similarly, absence epilepsy is a differential diagnosis of ADHD but is also considered to be a frequent comorbidity, occurring in 30 to 60% of children with absence epilepsy. 80 The prevalence of the ADHD phenotype in benign childhood epilepsy with centrotemporal spikes (rolandic epilepsy) lies at 64 to 65%, 81 and is possibly related to the occurrence of febrile convulsions. 82 The literature often does not draw a clear distinction between an ADHD phenotype, which includes all types of etiologies and causes, and a yet to be specified developmental ADHD “genotype.” Some authors use terms, such as “idiopathic” ADHD, 83 “primary,” or “genotypic” ADHD, 84 in contrast to ADHD of circumscribed origin other than developmental, the latter being referred to as ADHD “phenotype,” or “phenocopy,” 85 or “ADHD-like.” 86 “Secondary ADHD” usually refers to newly acquired ADHD symptoms arising after a known event or incident, for example, a head trauma or stroke. After early childhood stroke, the ADHD phenotype occurs in 13 to 20% of cases, and after pediatric traumatic brain injury, ADHD symptoms are observed in 15 to 20% of children. 87 Having ADHD considerably increases the risk of suffering a traumatic brain injury, 88 89 90 and most studies on secondary ADHD after traumatic brain injury control for or compare with premorbid ADHD (e.g., Ornstein et al 91 ). Whether and to what extent “phenotypic” and “genotypic” ADHD need to be distinguished on a phenomenological level is not clear. It is possible that shared neurobiological mechanisms will prevail and that genetic vulnerability and epigenetic factors may play a role in both types. For example, James et al 86 compared neurophysiological markers in two groups of adolescents with ADHD, one born very preterm and the other born at term. While the authors found very similar ADHD-specific markers in the two groups, some additional deficits only emerged in the preterm group, indicating more severe impairment. Other examples are rare genetic diseases with known genetic defects, which are often comorbid with ADHD. One may ask whether, for example, ADHD in Turner's syndrome should be considered as a rare genetic ADHD variant and count as genotypic ADHD, or whether it results from a different genetic etiology, with the status of an ADHD phenotype.

Clinical Diagnostic Procedure

Clinical assessment in children should mainly be based on a clinical interview with parents, including an exploration of the problems, the detailed developmental history of the child including medical or psychiatric antecedents, information on family functioning, peer relationships, and school history. According to the guidelines of the National Institute for Health and Care Excellence (NICE) in the United Kingdom, this may also include information on the mental health of the parents and the family's economic situation. The child's mental state should be assessed, possibly using a standardized semistructured clinical interview containing ADHD assessments (e.g., Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime version, DSM-5) 92 93 and by observer reports. The exploration should cover behavioral difficulties and strengths in several life contexts, for example, school, peer relationships, and leisure time. The use of informant rating scales, such as Conners' Rating Scales, 3rd edition, 94 or the Strengths and Difficulties Questionnaire 95 may be useful, but diagnosis should not be solely based on rating scales (NICE, AWFM ADHD). 96 97 A further interview should be conducted with the child or adolescent to gain a picture of the patient's perspective on current problems, needs, and goals, even though self-reports are considered less reliable for diagnosis. Information should also be obtained from the school, for example, by face-to-face or telephone contact with the teacher and, if possible, by direct school-based observation. A medical examination should be performed to exclude somatic causes for the behavioral symptoms and to gain an impression of the general physical condition of the patient. Current guidelines do not recommend including objective test procedures (intelligence and neuropsychological tests), neuroimaging, or neurophysiological measures in routine ADHD assessment but do suggest their use as additional tools when questions about cognitive functions, academic problems, coexisting abnormalities in electroencephalography (EEG), or unrecognized neurological conditions arise. After completion of the information gathering, the NICE guidelines recommend a period of “watchful waiting” for up to 10 weeks before delivering a formal diagnosis of ADHD. A younger age of the diagnosed child relative to his/her classmates has to be mentioned as one of the many pitfalls in the assessment of ADHD. It has been shown that the youngest children in a class have the highest probability of being diagnosed with ADHD and of being medicated with stimulants. 98

There is consensus that the diagnosis of ADHD requires a specialist, that is, a child psychiatrist, a pediatrician, or other appropriately qualified health care professionals with training and expertise in diagnosing ADHD. 97

Current Neurobiological and Neuropsychological Concepts

Neuropsychology, neuropsychological pathways and subgroups.

ADHD is related to multiple underlying neurobiological pathways and heterogeneous neuropsychological (NP) profiles. Twenty-five years ago, ADHD was characterized as a disorder of inhibitory self-control, 54 and an early dual pathway model distinguished between an inhibitory/executive function pathway and a motivational/delay aversion pathway (also called “cool” and “hot” executive function pathways in later publications), which are related to distinct neurobiological networks. 99 100 101 Still, the two systems may also interact. 102

Since then, other pathways have been added, such as time processing, 103 but a definitive number of possible pathways is difficult to define. For example, Coghill and colleagues 104 differentiated six cognitive factors in children with ADHD (working memory, inhibition, delay aversion, decision-making, timing, and response time variability) derived from seven subtests of the Cambridge neuropsychological test automated battery. Attempts to empirically classify patients into subgroups with selective performance profiles departing from comprehensive NP data collection were inconclusive. For example, using delay aversion, working memory, and response-time tasks, Lambek and colleagues 105 expected to differentiate corresponding performance profile subgroups in children with ADHD. However, their analysis resulted in subgroups differentiated by the severity of impairments, and not by selective profiles. Other empirical studies using latent profile or cluster analysis of NP tasks in large ADHD samples have differentiated three 106 107 or four 108 NP profile groups, which all included children with ADHD, as well as TD children, differing in severity but not in the type of profile. This might indicate that the identified NP deficit profiles were not ADHD-specific, but rather reflected characteristic distributions of NP performances, which are also present in the general population, with extreme values in children with ADHD. Some other empirical studies in the search for subgroups, however, identified ADHD-specific performance profiles (“poor cognitive control,” 109 “with attentional lapses and fast processing speed” 110 ), among other profiles being shared with TD controls. Obviously, divergent results regarding subgrouping may also be related to differing compilations of tested domains, consequently leading to a limited comparability of these studies.

Which Neuropsychological Functions are Impaired in ADHD and When?

A meta-analysis conducted in 2005 identified consistent executive function deficits with moderate effect sizes in children with ADHD in terms of response inhibition, vigilance, working memory, and planning. 67 Since then, a vast number of studies on NP deficits in children with ADHD compared with TD controls have been published. A recent meta-analysis included 34 meta-analyses on neurocognitive profiles in ADHD (all ages) published until 2016, referring to 12 neurocognitive domains. 111 The authors found that 96% of all standardized mean differences were positive in favor of the control group. Unweighted effect sizes ranged from 0.35 (set shifting) to 0.66 (reaction time variability). Weighted mean effect sizes above 0.50 were found for working memory (0.54), reaction time variability (0.53), response inhibition (0.52), intelligence/achievement (0.51), and planning/organization (0.51). Effects were larger in children and adolescents than in adults. The other domains comprised vigilance, set shifting, selective attention, reaction time, fluency, decision making, and memory.

Nearly every neuropsychological domain has been found to be significantly impaired in ADHD compared with TD controls, though effect sizes are often small. This includes, for example, altered perception (e.g., increased odor sensitivity 112 ; altered sensory profile 113 ; impaired yellow/blue color perception, e.g., Banaschewski et al, 114 for review, see Fuermaier et al 115 ), emotional tasks (e.g., facial affect discrimination), 116 social tasks (e.g., Marton et al 117 ), communication, 118 and memory. 119 Several of the described impairments may be related to deficient top-down cognitive control and strategic deficits, 120 121 122 but there is also evidence for basic processing deficits. 123

Neuropsychological Deficits as Mediators of Gene-Behavior Relations

A vast amount of research has been devoted to the search for neuropsychological endophenotypes (or intermediate phenotypes) for ADHD, that is, neurobiologically based impairments of NP performance characteristic of the disorder that may also be found in nonaffected close relatives. ADHD neuropsychological endophenotypes are assumed to mediate genetic risk from common genetic variants. 124 So far, deficits in working memory, reaction-time variability, inhibition, time processing, response preparation, arousal regulation, and others have been identified as probable endophenotypes for ADHD. 124 125 126 127 Genetic studies indicate an association of an ADHD-specific polygenetic general risk score (i.e., the total number of genetic variants that may be associated with ADHD, mostly related to dopaminergic transmission) with working memory deficits and arousal/alertness, 124 or with a lower intelligence quotient (IQ) and working memory deficits, 128 respectively. More specifically, a link of ADHD-specific variants of DAT1 genes with inattention and hyperactivity symptoms seems to be mediated by inhibitory control deficits. 129

Individual Cognitive Profiles and the Relevance of Cognitive Testing for the Clinical Assessment

Heterogeneity is found with regard to profiles, as well as with regard to the severity of cognitive impairment in individuals with ADHD, as measured by standardized tests. ADHD does not necessarily come with impaired neuropsychological test performance: about one-third of children with ADHD will not present any clinically relevant impairment, while another one-third shows unstable or partial clinical impairment, and about another one-third performs below average in NP tests. The classic concept of NP impairment, which assumes relative stability over time, possibly does not apply to NP deficits observed in ADHD, or only to a lesser extent. For the larger part, the manifestation of performance deficits may depend on contextual factors, 130 such as reward, or specifically its timing, amount, and nature, or on energetic factors, 131 for example, the rate of stimulus presentation or the activation provided by the task.

Many studies have shown that behavioral ratings of ADHD symptoms or questionnaires on executive function deficits are not, or at best weakly, correlated with NP test performance, even when both target the same NP domain. 132 133 In consequence, questionnaires on executive functioning are not an appropriate replacement for neuropsychological testing. Likewise, ADHD symptom rating scales do not predict results of objective attention or executive function tests and vice versa. Although mild intellectual disability and low IQ are more typically associated with the disorder, ADHD can be encountered across the entire IQ spectrum, including highly gifted children. 134 Therefore, an intelligence test should be part of the diagnostic procedure, but is not mandatory according to ADHD guidelines. In some children, intellectual difficulties and not ADHD may be the underlying cause for ADHD-like behaviors, while in other children with ADHD, academic underachievement despite a high IQ may be present.

It has been argued that symptoms defining ADHD may be understood as dimensional markers of several disorders belonging to an ADHD spectrum and, in consequence, the diagnosis of these behavioral symptoms should be the starting point for a more in-depth diagnosis rather than the endpoint. 135 This should include the cognitive performance profile. The ADHD behavioral phenotype predicts neither NP impairment nor intellectual achievement in the individual case, and objective testing is the only way to obtain an accurate picture of the child's cognitive performance under standardized conditions. Its goal is not ADHD classification, but rather to obtain the best possible understanding of the relation between cognitive functioning and behavioral symptoms for a given patient, to establish an individually tailored treatment plan.

Neurophysiology

Neurophysiological methods like EEG, magnetoencephalography, and event-related potentials (ERPs) as task-locked EEG averages capture brain functions in ADHD at high (ms) temporal resolution. The approach covers both fast and slow neural processes and oscillations, and clarifies the type and timing of brain activity altered in ADHD at rest and in tasks. It reveals neural precursors, as well as correlates, and consequences of ADHD behavior. 136 Neurophysiological and particularly EEG measures also have a long and controversial history as potential biomarkers of ADHD. Current evidence clarifies how multiple pathways and deficits are involved in ADHD at the group level, but recent attempts toward individual clinical translation have also revealed considerable heterogeneity, which does not yet support a clinical application for diagnostic uses or treatment personalization, as explained below.

Resting Electroencephalography

The EEG is dominated by oscillations in frequency bands ranging from slow δ (<4 Hz) and θ (4–7 Hz) via α (8–12 Hz) to faster β (13–30 Hz) and γ (30–100 Hz) band activity. The spectral profile reflects maturation and arousal, with slow frequencies dominating during early childhood and slow-wave sleep. Source models can link scalp topography to brain sources and distributed networks.

Initial studies suggested a robust link between ADHD diagnosis and resting EEG markers of reduced attention, hypoarousal, or immaturity, such as increased θ and an increased θ/β ratio (TBR). However, more recent studies, 137 138 some with large samples, 139 140 failed to replicate a consistent TBR increase in ADHD. Instead, the results indicated heterogeneous θ and β power deviations in ADHD not explained by ADHD subtype and psychiatric comorbidity. 141 A cluster analysis of EEG in children with ADHD also revealed considerable heterogeneity regarding θ excess and β attenuation in ADHD. While several clusters with EEG patterns linked to underarousal and immaturity could be identified, only three of the five EEG clusters (60% of the cases with ADHD) had increased θ. 139 Several recent θ and TBR studies that no longer found TBR association with ADHD diagnosis still replicated the reliable age effects, 137 138 142 confirming the high quality of these studies. Increasing sleepiness in adolescents, 143 or shorter EEG recordings, may have reduced the sensitivity to time effects and state regulation deficits in ADHD, 136 144 potentially contributing to these replication failures. Also, conceptualizing TBR as a marker of inattention or maturational lag may be too simple, since θ activity can also reflect concentration, cognitive effort, and activation. 145 146

During sleep, stage profiles reveal no consistent deviations in ADHD, but the slow-wave sleep topography is altered. In particular, frontal slow waves are reduced, leading to a more posterior topography as observed also in younger children. 147 This delayed frontalization can be interpreted as a maturational delay in ADHD, in line with a cluster of resting EEG, changes in task related ERPs during response inhibition, 148 and structural magnetic resonance imaging (MRI) findings. 149

Task Related Event-Related Potentials

Task-related processing measures, particularly ERPs, have critically advanced our understanding of ADHD through their high-time resolution, which can separate intact and compromised brain functions. ERPs have revealed impairments during preparation, attention, inhibition, action control, as well as error, and reward processing, with partly distinct networks but often present during different phases of the same task. In youth and adults with ADHD, the attentional and inhibitory P3 components and the preparatory contingent negative variation (CNV) component are most consistently affected, but state regulation and error or reward processing are also compromised. 136 150 Activity during preparation, attention, or inhibition is typically weaker and more variable but not delayed. This often occurs in task phases without visible behavior and precedes the compromised performance. Familial and genetic factors also modulate these markers of attention and control. Some impairment is also observed in nonaffected siblings or in parents without ADHD, 151 152 and genetic correlates often implicate the dopamine system. 125 Some ERP changes, like the attenuated CNV during preparation, remain stable throughout maturation, and are also markers of persistent ADHD, while other markers, such as the inhibition related P3, remain attenuated despite clinical remission. 148 153

Overall, the ERP results confirm attentional, cognitive, and motivational, rather than sensory or motor impairments in ADHD, in line with current psychological and neurobiological models. However, different ERP studies hardly used the same tests and measures, so valid statements regarding classification accuracy and effect size are particularly difficult, 154 and there is an urgent need for meta-analyses regarding the different ERPs.

Clinical Translation

Despite published failures to replicate robust TBR based classification of ADHD, a TBR-based EEG test was recently approved by the U.S. Food and Drug Administration to assist ADHD diagnosis. 155 Although not promoted as a stand-alone test, children with suspected ADHD, and increased TBR were claimed to likely meet full diagnostic criteria for ADHD; while children with suspected ADHD but no TBR increase should undergo further testing, as they were likely to have other disorders better explaining ADHD symptoms (see also DSM-5 exclusionary criterion E).

This multistage diagnostic approach could possibly identify a homogeneous neurophysiological subgroup, but it omits critical elements of careful, guideline-based ADHD diagnostics. Reliability and predictive value of the TBR remain untested, and the increasing evidence for poor validity of TBR renders it unsuitable for stand-alone ADHD diagnosis. Accordingly, the use of TBR as a diagnostic aid was broadly criticized. 156 157

In sum, the recent literature suggests that neither TBR nor other single EEG or ERP markers are sufficient to diagnose ADHD and are not recommended for clinical routine use, in line with the increasing evidence for heterogeneity in ADHD.

Combining measures across time, frequency, and tasks or states into multivariate patterns may better characterize ADHD. The potential of such approaches is evident in improved classification using machine-learning algorithms based on combinations of EEG measures 142 or EEG and ERP measures. 138 158 However, claims of high-classification accuracies up to 95% (e.g., Mueller et al 158 ) require further independent replication and validation with larger samples, and plausible mapping to neural systems and mechanisms. Modern pattern classification is particularly sensitive to uncontrolled sample characteristics and needs validation through independent large samples. 159

Focusing on EEG-based prediction rather than diagnosis may hold more promise for clinical translation, and may utilize the EEG heterogeneity in clinical ADHD samples. For example, early studies on predicting stimulant response suggested that children with altered wave activity, in particular increased TBR, θ or α slowing, respond well to stimulant medication. However, in recent prospective work with a large sample, TBR was not predictive, and α slowing allowed only limited prediction in a male adolescent subgroup. 160

Predicting response to intense nonpharmacological treatment is of particular interest given the high costs and time requirements. Promising findings have been reported for one neurofeedback study, where α EEG activity and stronger CNV activity together predicted nearly 30% of the treatment response. 161 Still, the lack of independent validation currently allows no clinical application.

In conclusion, neurophysiological measures have clarified a rich set of distinct impairments but also preserved functions which can also serve as markers of persistence or risk. These markers may also contribute in the classification of psychiatric disorders based on neuromarkers (research domain criteria approach). As potential predictors of treatment outcome they may support precision medicine, and proof-of-concept studies also highlight the potential of multivariate profiling. The findings also demonstrate the challenge with this approach, including notable replication failures, and generalizability of most findings remains to be tested. Neurophysiological markers are not ready to serve as tools or aids to reliably diagnose ADHD, or to personalize ADHD treatment in individual patients.

Neuroimaging

Modern brain imaging techniques have critically contributed to elucidating the etiology of ADHD. While MRI provides detailed insights into the brain microstructure, such as for example gray matter volume, density, cortical thickness, or white matter integrity, fMRI allows insights into brain functions through activation and connectivity measures with high–spatial resolution.

Delayed Maturation and Persistent Alterations in the Brain Microstructure in ADHD

The brain undergoes pronounced developmental alterations in childhood and adolescence. Gray matter volume and cortical thickness show nonlinear inverted U -shaped trajectories of maturation with a prepubertal increase followed by a subsequent decrease until adulthood while white matter volume progressively increases throughout adolescence and early adulthood in a rather linear way. 162 163 164 165 Large variations of the maturational curves in different brain regions and subregions suggest that phylogenetically older cortical areas mature earlier than the newer cortical regions. Moreover, brain areas associated with more basic motor or sensory functions mature earlier than areas associated with more complex functions including cognitive control or attention. 163 164 Altered maturation of the cortex for ADHD has been reported for multiple areas and cortical dimensions, 166 167 mainly in the form of delayed developmental trajectories in ADHD but recently also as persistent reductions, particularly in the frontal cortex. 168 Such findings speak for delayed maturation in specific areas rather than a global developmental delay of cortical maturation in ADHD. Microstructural alterations in ADHD have been associated with a decreased intracranial volume 169 and total brain size reduction of around 3 to 5%. 100 168 170 In accordance, increasing ADHD symptoms in the general population correlated negatively with the total brain size. 171 A meta-analysis (Frodl et al) and a recent cross-sectional mega- and meta-analysis (Hoogman et al) indicate that such reductions in brain volume may be due to decreased gray matter volumes in several subcortical structures, such as the accumbens, amygdala, caudate, hippocampus, and putamen but also cortical areas (prefrontal, the parietotemporal cortex) and the cerebellum. 170 172 173 174 175 176 177 Effects sizes of subcortical alterations were highest in children with ADHD and the subcortical structures showed a delayed maturation. 169 Moreover, higher levels of hyperactivity/impulsivity in children were associated with a slower rate of cortical thinning in prefrontal and cingulate regions. 167 178 Differences in brain microstructure have also been reported in a meta-analysis for white matter integrity as measured with diffusion tensor imaging in tracts subserving the frontostriatal-cerebellar circuits. 179 To summarize, diverse neuroanatomical alterations in total brain volume and multiple cortical and subcortical dimensions characterize ADHD. These alterations are most pronounced in childhood and suggest a delayed maturation of specific cortical and subcortical areas along with some persistent reductions in frontal areas in a subgroup of ADHD patients with enduring symptoms into adulthood.

Alterations in the Brain Function of Specific Networks in ADHD

Specific functional networks, mainly those involved in inhibition, attention processes, cognitive control, reward processing, working memory, or during rest have been intensively studied in ADHD using fMRI in the past. Alterations have been reported in the corresponding brain networks and the main findings are summarized below.

Atypical Resting State Connectivity in Children with ADHD

Resting state examines spontaneous, low frequency fluctuations in the fMRI signal during rest, that is , in absence of any explicit task. 180 Resting state networks describe multiple brain regions for which the fMRI signal is correlated (functionally connected) at rest, but the same networks may coactivate also during task-based fMRI. 181 One important resting state network, the so-called default mode network (DMN), comprises brain areas that show higher activation during wakeful rest and deactivations with increasing attentional demands. 182 183 While the DMN usually shows decreasing activation with increasing attentional demands, the cognitive control network shows an opposite pattern and increases its activation. This inverse correlation of DMN and the cognitive control networks is diminished or absent in children and adults with ADHD and may explain impaired sustained attention through attentional lapses that are mediated by the DMN. 181 184 185 186 In addition, a more diffuse pattern of resting state networks connectivity and a delayed functional network development in children with ADHD have been reported. 187 Finally, atypical connectivity in cognitive and limbic cortico-striato-thalamo-cortical loops of patients with ADHD suggest that the neural substrates may either reside in impaired cognitive network and/or affective, motivational systems. 181

Altered Processing of Attention and Inhibition in Fronto-basal Ganglia Circuits in ADHD

Meta-analyses summarizing the findings of functional activation studies report most consistent alterations in brain activation patterns as hypoactivation of the frontoparietal network for executive functions and the ventral attention system for attentional processes in children with ADHD. 188 189 190 More specifically, motor or interference inhibition tasks yielded consistent decreases in a (right lateralized) fronto-basal ganglia network comprising supplementary motor area, anterior cingulate gyrus, left putamen, and right caudate in children with ADHD. 189 190 For tasks targeting attentional processes, decreased activation in a mainly right lateralized dorsolateral fronto-basal ganglia-thalamoparietal network characterized children with ADHD. Depending on the task, hyperactivation can cooccur in partly or distinct cerebellar, cortical, and subcortical regions. 188 189 190

Altered Reward Processing and Motivation

Emotion regulation and motivation is mediated by extended orbitomedial and ventromedial frontolimbic networks in the brain. 191 Abnormal sensitivity to reward seems to be an important factor in the etiology of ADHD as suggested by several models of ADHD, 192 193 194 mainly due to a hypofunctioning dopaminergic system. 195 In accordance, impairments in specific signals that indicate violations of expectations, the so called reward prediction errors (RPE), were shown in the medial prefrontal cortex of adolescents with ADHD during a learning task. 196 RPE signals are known to be encoded by the dopaminergic system of the brain, and deficient learning and decision making in ADHD may thus be a consequence of impaired RPE processing. 196 Abnormal activation has also been reported for the ventral striatum during reward anticipation and in other cortical and subcortical structures of the reward circuitry. 197

Normalization of Atypical Activation and Brain Structural Measures after Treatment

Stimulant medication and neurofeedback studies have pointed to a certain normalization of dysfunctional activation patterns in critical dorsolateral frontostriatal and orbitofrontostriatal regions along with improvements in ADHD symptoms. 198 199 200 201 Also, brain microstructure, especially the right caudate, has shown some gradual normalization with long-term stimulant treatment. 176 190

To conclude, a wide range of neuroimaging studies reveal relatively consistent functional deficits in ADHD during executive functions, including inhibitory control, working memory, reward processes, and attention regulation but also during rest. Some of these alterations are more persistent, others are specific to children and may thus represent a developmental delay. Specific treatments showed trends toward a normalization of alterations in brain microstructure and functional networks.

Genetic Associations with ADHD and ADHD Related Traits

From family studies, as well as twin studies, the heritability for ADHD has been estimated to be between 75 upto 90%. 202 Moreover, the heritability was found to be similar in males and females and for inattentive and hyperactive-impulsive components of ADHD. 202 Interestingly, a strong genetic component was also found when the extreme and subthreshold continuous ADHD trait symptoms were assessed in the Swedish twins. 19 Even over the lifespan, adult ADHD was found to demonstrate high heritability that was not affected by shared environmental effects. 203 Recently, structural and functional brain connectivity assessed in families affected by ADHD has been shown to have heritable components associated with ADHD. 204 Similarly, the heritability of ERPs elicited in a Go/No-Go-task measuring response inhibition known to be altered in ADHD, was found to be significantly heritable. 205

In several studies, ADHD-related traits have also shown significant heritability. For example, in two independent, population based studies, significant single nucleotide polymorphism heritability estimates were found for attention-deficit hyperactivity symptoms, externalizing problems, and total problems. 206 In another study, investigating the two opposite ends of ADHD symptoms, low-extreme ADHD traits were significantly associated with shared environmental factors without significant heritability. 207 While on the other hand, high-extreme ADHD traits showed significant heritability without shared environmental influences. 207 A crossdisorder study including 25 brain disorders from genome wide association studies (GWAS) of 265,218 patients and 784,643 controls, including their relationship to 17 phenotypes from 1,191,588 individuals, could demonstrate significant shared heritability. 208 In particular, ADHD shared common risk variants with bipolar disorder, major depressive disorder, schizophrenia, and with migraine. 208 Indeed, in general, population-based twin studies suggest that genetic factors are associated with related-population traits for several psychiatric disorders including ADHD. 209 This suggests that many psychiatric disorders are likely to be a continuous rather than a categorical phenotype.

Though ADHD was found to be highly heritable, the underlying genetic risk factors are still not fully revealed. The current consensus suggests, as in many other psychiatric disorders, a multifactorial polygenic nature of the common disorder. Both common genetic variants studied by hypothesis-driven candidate gene association or by the hypothesis-free GWAS could only reveal the tip of the iceberg. Through the candidate gene approach, only very few findings could show replicable significant association with ADHD, as reported by meta-analysis studies for the dopaminergic, noradrenergic, and serotonergic genes. 210 211 Several GWAS have been conducted followed by meta-analysis, which again failed reaching genome-wide significant results. 212 213 214 215 216 217 218 219 220 221 222 223 224 However, recently, the first genome-wide significance has been reached in a GWAS meta-analysis consisting of over 20,000 ADHD patients and 35,000 controls. 225 Twelve independent loci were found to significantly associate with ADHD, including genes involved in neurodevelopmental processes, such as FOX2 and DUSP6 . 225 But even in these findings the effect sizes are rather small to be used for diagnostic tools. Therefore, polygenic risk score approaches have emerged as a possible tool to predict ADHD. 202 Yet this approach needs further investigation now that genome-wide significance has been reached by Demontis et al. 225 However, at this point, it is not yet possible to exclude that rare SNPs of strong effect may also be responsible (similar to breast cancer) for a small proportion of ADHD cases due to the heterogeneity of symptomatology, illness course, as well as biological marker distribution, as outlined above.

Multimodal Treatment of ADHD

A variety of national and international guidelines on the assessment and management of ADHD have been published over the last 10 years, not only for clinicians but also for patients and caregivers. 96 97 226 227 228 All guidelines recommend a multimodal treatment approach in which psychoeducation forms a cornerstone of the treatment and should be offered to all of those receiving an ADHD diagnosis, as well as to their families and caregivers.

According to the NICE Guidelines, the first step is always a planning process for the multimodal treatment with respect to the psychological, behavioral, and occupational or educational needs of the child and his/her family. 97 This planning phase could be organized as a “round table” with the child, parents, and other caregivers. The following aspects should be taken into account: the severity of ADHD symptoms and impairment, the relative impact of other neurodevelopmental or mental health conditions and how these affect or may affect everyday life (including sleep). In addition, resilience and protective factors, as well as the goals of the child and family, should be considered in the intervention process. The participation of child and parents in the planning and treatment process is more centrally outlined in recent guidelines and is emphasized in detail for the different treatment steps (e.g., NICE and S3 Guidelines). 96 97 The participation process is not just a one-time dialogue but should rather continue throughout all steps of the treatment process. Benefits and harms of nonpharmacological and pharmacological treatments should be discussed carefully and on the basis of the latest evidence. Preferences and concerns, and the importance of adherence to treatment, should be discussed and taken into account within the treatment process. Patients and their families or caregivers should be reassured, as appropriate that they can revisit decisions about treatments.

Multimodal treatment approaches also advocate a systematic adaptive procedure that combines different treatment modules according to the needs and situation of the patient and family. This may, for instance, include a first stage in which parent counseling is initiated, a second-stage encompassing, for example, individual behavioral therapy for the child, while the parents participate in a parent training program in parallel, followed by a third stage in which stimulant medication is started, etc. 229 230 Environment-centered interventions aim at the counseling or training of parents or the instruction of teachers at school or preschool. Parent training programs may be administered individually or in groups and have shown positive effects on parenting skills, ADHD behavior, and comorbid conduct problems. 231 232 233 Family therapy for ADHD focuses on the ADHD family, with the ADHD patient being a part of the family system with dysfunctional interactional patterns. 234 School-based interventions may target (1) the conditions in the classroom, for example, by minimizing distractions; (2) the instruction of the teacher, for example, by suggesting more appropriate teaching methods or by promoting peer tutoring; or (3) the student, for example, by improving self-management and social skills, or by helping to cope with stigma. 235 236 237

Pharmacological Approaches

Starting medication.

All medication for ADHD should only be initiated by a health care professional with training and expertise in diagnosing and managing ADHD. The expert should be familiar with the pharmacokinetic profiles and bioavailability of all the short- and long-acting preparations available for ADHD. The following parameters should be considered before first medication: medical history of the child but possibly also of the parents, current medication, height and weight, baseline pulse and blood pressure, a cardiovascular assessment, and an electrocardiogram if the treatment may affect the QT interval. A cardiology expert opinion should be sought before starting medication for ADHD if there is a history of congenital heart disease, previous cardiac surgery, or a history of sudden death in a first-degree relative under the age of 40 years, or if the blood pressure is consistently above the 95th centile for age and height for children and young people.

Age-Specific Needs

Treatment recommendations are often based on the specific needs of children, youth, or adults. 97 226 According to the NICE guidelines 97 and also pharmacological recommendations (e.g., Walitza and colleagues 238 239 ), a distinction should also be made between children under 5 years of age or preschool children, and school children. For the younger children (under 5 years of age), parent or career training programs and parent group training programs are always first-line treatments. Medication for children under 5 years with ADHD should only be given following a second specialist opinion from an ADHD service with expertise in managing ADHD in young children (ideally from a tertiary service). For children over 5 years of age, education and information about the causes and impact of ADHD and advice on parenting strategies should be offered, as well as liaison with school, college, or university if consent to do so is provided. 97 Children aged 5 years and over and young people should only receive medication if the ADHD symptoms are still causing a persistent significant impairment in at least one life domain after environmental modifications have been implemented and evaluated.

Selection of Pharmacotherapy

In Europe, methylphenidate either as short- or long-acting preparation is the first-line medication for ADHD across the life span. Second-line medications are lisdexamfetamine, atomoxetine, and guanfacine. A switch to lisdexamfetamine is only recommended if children have first undergone at least a 6-week trial of methylphenidate at an adequate dose and have not derived sufficient benefit in terms of reduced ADHD symptoms and associated impairment, or if patients experience adverse side effects. 238 The Canadian Guidelines (2018) recommend an individual treatment approach, which can start with different options, and if medication is to be used, long-acting formulations of psychostimulants or atomoxetine are always the first choice. 226 Comorbid disorders may necessitate adjustments to the treatment plan or alternative treatments.

According to the NICE guidelines, atomoxetine and guanfacine should only be offered if patients cannot tolerate methylphenidate or lisdexamfetamine or if their symptoms have not responded to separate 6-week trials of methylphenidate and lisdexamfetamine, having considered alternative preparations and adequate doses. 97

Evidence for ADHD Medications

In the first “gold standard” study comparing the different treatment approaches for ADHD alone and in combination (National Institute of Mental Health Collaborative Multimodal Treatment Study of Children with ADHD [MTA study]), the effects of both pharmacological therapy (methylphenidate and intensive counseling) and of multimodal therapy (methylphenidate and intensive behavioral therapy) were significantly more effective after 14 months than behavioral therapy alone or than the “standard” therapy (treatment as usual in the community) of the control group. The multimodal therapy was not significantly superior to pharmacological therapy alone, but did result in significant improvements in ADHD symptoms at a lower dosage of methylphenidate. 240 241 242 Since the MTA study, numerous studies have investigated methylphenidate, amphetamine, and nonstimulants like atomoxetine or α 2 -adrenoceptor agonists, such as clonidine and guanfacine, regarding different aspects of effectiveness and tolerability.

The psychostimulants methylphenidate and amphetamine are the most effective agents for the treatment of core ADHD symptoms, with a favorable efficacy and adverse event profile. 243 244 245 Compared with methylphenidate and amphetamine, which both show immediate symptom reduction, the full effects of atomoxetine and guanfacine on reducing ADHD symptoms usually only unfold after some weeks of administration. Atomoxetine and guanfacine are not controlled substances, and are licensed in various European countries and in the United States for treatment of ADHD in children above the age of 6 years. Both have been shown to be effective in decreasing ADHD core symptoms with an effect size of around 0.7, which is somewhat lower than the effect size for methylphenidate, depending on the underlying studies (e.g., Sallee et al 246 ).

Management Strategies and Duration of Pharmacological Treatment

Following an adequate dosage of medication ( Table 1 ) and treatment response, medication for ADHD should be titrated to an optimized dosage with regard to the clinical efficacy, safety, and side effects, which should be continued for as long as it remains clinically necessary and effective. This should be reviewed at least annually, also with a planned “medication break” to decide whether there is a continuing need for care. 238 239 However, there is little available empirical evidence to guide clinicians on questions, such as the optimum duration of treatment and when it is appropriate to consider drug discontinuation. As ADHD can persist into adulthood, decisions on treatment discontinuation need to be taken on a case-by-case basis. 226

Abbreviations: ADHD, attention deficit hyperactivity disorder; max. maximum.

Adapted from (1) Walitza S, Romanos M, Greenhill LL, Banaschewski T. Attention-Deficit/Hyperactivity Disorders. In: Gerlach M, Warnke A, Greenhill LL, eds. Psychiatric Drugs in Children and Adolescents. Wien: Springer; 2014:369–381 238 and (2) Walitza S, Gerlach M, Romanos M, Renner T. Psychostimulanzien und andere Arzneistoffe, die zur Behandlung der Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) angewendet werden. In: Gerlach M, Mehler-Wex C, Walitza S, Warnke A, Wewetzer C, eds. Neuro-/Psychopharmaka im Kindes- und Jugendalter: Grundlagen und Therapie. Berlin, Heidelberg: Springer Berlin Heidelberg; 2016:289–331. 239

Among the most frequent side effects of psychostimulant therapy ( Table 2 ) are reduced appetite and sleep disturbances. 247 Appetite reduction following treatment initiation with an ADHD drug often attenuates with time. Reduced appetite at mealtimes can be avoided by taking the medication after meals rather than before. Should a clinically significant lack of appetite persist, dosage reduction (by one-fourth or half tablet of methylphenidate), discontinuation (rarely necessary), or switching to a different formulation or medication should be considered.

Adapted from (1) Walitza S, Romanos M, Greenhill LL, Banaschewski T. Attention-Deficit/Hyperactivity Disorders. In: Gerlach M, Warnke A, Greenhill LL, eds. Psychiatric Drugs in Children and Adolescents. Wien: Springer; 2014:369–381 238 ; (2) Walitza S, Gerlach M, Romanos M, Renner T. Psychostimulanzien und andere Arzneistoffe, die zur Behandlung der Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) angewendet werden. In: Gerlach M, Mehler-Wex C, Walitza S, Warnke A, Wewetzer C, eds. Neuro-/Psychopharmaka im Kindes- und Jugendalter: Grundlagen und Therapie. Berlin, Heidelberg: Springer Berlin Heidelberg; 2016:289–331 239 ; (3) Huang YS, Tsai MH. Long-term outcomes with medications for attention-deficit hyperactivity disorder: current status of knowledge. CNS Drugs 2011;25:539–554; (4) Storebo OJ, Pedersen N, Ramstad E et al. Methylphenidate for attention deficit hyperactivity disorder (ADHD) in children and adolescents - assessment of adverse events in non-randomized studies. Cochrane Database Syst Rev 2018;5:CD012069284; and (5) Wigal T, Greenhill L, Chuang S et al. Safety and tolerability of methylphenidate in preschool children with ADHD. J Am Acad Child Adolesc Psychiatry 2006;45:1294–1303.

Nonpharmacological Treatments

Cognitive behavioral therapy.

Cognitive behavioral therapy (CBT) is a form of behavioral intervention which aims at reducing ADHD behaviors or associated problems by enhancing positive behaviors and creating situations in which desired behaviors may occur. In the case of preschool and young school children, CBT focuses on parents and educators, who are instructed and trained to act according to CBT principles, while older children and adolescents may be trained directly to use more appropriate behavioral strategies. 248 CBT and its more specific forms (e.g., social skills training, training of planning and organizational skills, and self-management techniques) have positive effects on behavior, parenting skills, child–parent relationships, and certain daily living skills, 232 249 although effects on ADHD core symptoms are inconsistent and relatively low when only blinded assessments are considered. 250 A recent meta-analysis suggested that the combined treatment of medication with CBT is more efficacious than stimulant medication alone (with an estimated standardized mean difference of 0.5). 251

Neuropsychological Treatments

In cognitive training interventions, either PC-supported or in a manualized format, cognitive exercises that tap into cognitive domains, such as working memory or inhibitory control, are performed in a repetitive manner and with increasing difficulty. The evidence base for this type of intervention is poor according to recent studies (e.g., Bikic et al 252 ) and metastudies (e.g., Cortese et al 253 ). While some “near-transfer” improvements in neuropsychological tests tapping into the trained domain are probable, the evidence for “far transfer” to academic achievements or to the ADHD symptom level is weak. Most studies, however, used the same kind of cognitive training with all participants, irrespective of their actual individual cognitive difficulties. Moreover, they did not adhere to theoretically based training principles, which recommend domain-specific training for the functional improvement of a selective neuropsychological deficit. Possibly, future approaches that combine repetitive exercise and top-down strategy application may provide larger benefits for children with ADHD.

In neurofeedback training (NF), EEG activity measured by one or more electrodes applied to the head is transformed into a visual or acoustic signal and fed back online, for example, by a stimulus moving up and down. By steering the stimulus on the screen, the participant may gain control over his/her EEG activity. Many different training protocols have been applied to ADHD. Those which have received the best evaluation are the NF training of the θ/β frequency bands ratio (the goal is generally to decrease θ and to increase β frequencies) and the training of slow cortical potentials (learning to intentionally increase and decrease cortical excitability over short periods of time). However, “normalizing” an ADHD-specific deviant EEG pattern can no longer qualify as a meaningful goal, as no characteristic ADHD pattern seems to exist (Loo et al, 254 see neurophysiology section), although gaining control over one's brain activity and over attentional states continues to be a valid treatment goal. According to parent ratings, clinical improvements after NF are stronger and longer-lasting compared with other behavioral treatment methods, but teacher ratings usually fail to yield significant effects. 255 Recent research has focused on the specificity of treatment effects, defined as the association between the learned regulation of EEG activity and the behavioral outcome. 256 To date, there is no convincing evidence that the learned control over brain activity is responsible for the observed behavioral improvements. Instead, nonspecific treatment effects, such as improved self-efficacy, positive reinforcement, and learning to sit still, seem to contribute in large part to the positive clinical outcome.

Methodologically more sophisticated NF approaches, such as tomographic NF, 257 fMRI-NF, 258 or near-infrared spectroscopy feedback (feedback of hemoglobin oxygenation) 259 are still in the experimental stage.

Noninvasive Brain Stimulation

Repetitive transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) represent other potential means to modulate cortical activity. Therefore, these approaches may also be promising in terms of improving clinical and cognitive ADHD symptoms such as inattention and impulsiveness. 258 260 261 262 Based on a meta-analysis, Westwood et al 263 suggested that left and/or right prefrontal stimulation may improve performance in attention, inhibition and/or working memory tasks. However, these approaches are not yet recommended by therapy guidelines.

Alternative Nonpharmacological Treatment Methods

Mindfulness training, physical activity, and yoga seem to have positive effects on ADHD behavior, but for the time being, the scientific evidence is weak and these treatments are seen at best as complementary to other interventions. 264 265 266 267 268 Digital home treatment programs or support apps are currently being developed for ADHD patients or their parents 269 270 ; their usefulness or clinical validity still needs to be tested. Children and adolescents with ADHD often show a great affinity with digital media, which may improve compliance, but one has to take into account that the rate of problematic internet use and gaming is enhanced in youth with ADHD (estimated at 37% in ADHD vs. 12% in TD). 271 Free fatty acid supplementation has been described to bring about small but significant reductions in ADHD symptoms even with probably blinded assessments (standardized mean difference = 0.16). 250

Long-Term Outcome

Follow-up studies have reported divergent results, with some reporting high rates of persistence until adulthood (up to 79%), 153 and others showing much higher rates of remission from childhood to adolescence (e.g., 45–55% of syndromal remissions). 272 273 274 Recent population-based studies from Brazil, the United Kingdom, and New Zealand have claimed that a large portion of de novo ADHD cases emerge at adult age, 275 276 277 but these results can probably be explained by methodological artifacts and missed subthreshold cases. 76 278 279 However, meta-analytic findings by Bonvicini et al 280 indicate that in part, different genes and polymorphisms seem to contribute to childhood ADHD and adulthood ADHD, lending some genetic plausibility to findings of a late manifestation of the disorder. According to the MTA study, the contribution of interventions administered during childhood to outcome in adulthood is negligible, but controlled intervention was limited to a relatively short period of time (14 months). 281 Neurobiologically, the course of ADHD may be explained by different models. 274 According to the first model, remission at adult age may be reduced to the normalization of brain functions through maturation. A second model explains remission through the recruitment of compensatory brain functions. The third model claims that brain function anomalies show life-long persistence, even though behavioral dysfunction may have remitted. 274 Possibly, all of these models, and probably additional ones too (see e.g., Doehnert et al 148 ), apply to different subgroups of patients or functions and may account for the divergent results in the literature.

Conflict of Interest D.B. reports having served as an unpaid scientific advisor for an EU-funded neurofeedback trial unrelated to the present work.

S.W. reports grants from Gertrud Thalmann Fonds of the UPK Basel, Collaborative Project, grants from Ebnet Foundation, grants from Mensia Technologies SA & EU H2020 SME Instrument, grants from University Medical Center Utrecht & Stanley Medical Research Institute, Collaborative Project, grants from Swiss National Foundation, Investigator Initiated Clinical Trial, other from Thieme Neuropychopharmakologie des Kindes und Jugendalters, outside the submitted work; and S.W. has received in the last 5 years royalities from Thieme Hogrefe, Kohlhammer, Springer, Beltz. S.W. has received lecture honoraria from Opopharma in the last 5 years. Her work was supported in the last 5 years by the Swiss National Science Foundation (SNF), diff. EU FP7s, HSM Hochspezialisierte Medizin of the Kanton Zurich, Switzerland, Bfarm Germany, ZInEP, Hartmann Müller Stiftung, Olga Mayenfisch, Gertrud Thalmann Fonds. Outside professional activities and interests are declared under the link of the University of Zurich www.uzh.ch/prof/ssl-dir/interessenbindungen/client/web/ .

Research on ADHD

Current research, research agenda.

Attention-deficit/hyperactivity disorder (ADHD) is a serious public health problem affecting a large number of children and adults. CDC conducts research to expand on what is known about ADHD. The information learned will improve knowledge about the factors that increase the risk for ADHD, as well as the causes, and best treatments, and will aid the development of resources to help people living with ADHD . Learn more about CDC’s research on ADHD on this overview page.

ADHD can cause problems in how well children do in school, in their ability to make and keep friends, and in how they function in society. Although there are treatments to improve ADHD symptoms, more information is needed about managing ADHD so that children can learn and grow into adulthood without being impaired by their symptoms.

The criteria used to diagnose ADHD have changed over time. Researchers who study ADHD have used different definitions to diagnose ADHD. This has led to different estimates for the number, characteristics, and outcomes of children with the disorder. Although the exact causes of ADHD are not known, research shows that genes play a role, but other factors may contribute or make symptoms worse. There are many unanswered questions about ADHD, and there is more we need to learn about how ADHD affects people throughout their life.

The treatment costs of ADHD and the personal and societal costs can be significant. Researchers estimate that in the United States, $31.6 billion is the combined annual cost for

• Health care for persons with ADHD specifically related to the diagnosis;
• Health care for family members of persons with ADHD specifically related to their family member’s diagnosis; and
• Work absences among adults with ADHD and adult family members of persons with ADHD. 1

Improving the health of individuals with ADHD could result in substantial financial savings to families and society, potentially reducing this financial burden.

National Surveys

CDC uses data from national surveys to understand the number of children with ADHD, other concerns and conditions they might experience, and the kind of treatment they might receive. Surveys that have data on children and on ADHD include

• National Survey of Children’s Health since 2016 ,
• National Survey of Children’s Health 2003-2012 ,
• National Survey of the Diagnosis and Treatment of ADHD and Tourette Syndrome (NS-DATA) ,
• National Health Interview Survey ,
• National Survey on Children with Special Health Care Needs

Read about key findings from the national surveys .

Learn more about the data from the national surveys .

Policy Research

In order to fully appreciate how children with ADHD are treated, one must understand the policies that affect how treatments are authorized and reimbursed by health plans. One policy that may affect medication treatment is for health plans or state programs to require pre-authorization before specific medications can be prescribed. Prescription prior-authorization policy means that the health plan or state program is required to review a physician’s prescription request before coverage for the medication is granted.

Over the past decades, the number of children being prescribed ADHD medications has increased substantially. In response to this trend, many state Medicaid programs have implemented prior-authorization policies for pediatric use of ADHD medications. These policies vary from state to state, and no comprehensive information on these policies was previously available.

To learn more about prior-authorization policies related to pediatric use of ADHD medications, CDC collaborated with Temple University to conduct a cross-sectional mapping study . Information was gathered on state Medicaid prior-authorization policies (as of April 2023) for prescribing ADHD medication to children. The study team collected

New Research: Medicaid policies to manage the use of ADHD medications: Information by state

• Prior-authorization forms,
• Memoranda from state Medicaid directors to prescribers,
• Drug utilization review board meeting notes, and
• State prescription drug lists.

The study team developed a coding scheme to capture and catalogue the key features of the prior-authorization policies. You can access a fact sheet with a summary of the results of this mapping study and also a database of state policies.

Healthcare Claims Data

CDC uses healthcare insurance claims data to understand treatment patterns for children in clinical care for ADHD, such as claims for psychological services and ADHD medication in patients covered by employer-sponsored insurance or by Medicaid.

Read more about the data from healthcare claims datasets.

Community-based Research

CDC’s National Center on Birth Defects and Developmental Disabilities (NCBDDD) supported large community-based, epidemiologic studies of ADHD in the United States. These studies

• Enhance what is known about ADHD and the co-occurring conditions in children and
• Increase the opportunity to make the most informed decisions and recommendations about potential public health prevention and intervention strategies for children with ADHD.

Project to Learn About ADHD in Youth (PLAY)

The Project to Learn About ADHD in Youth (PLAY) was a population-based research project with the University of South Carolina and the University of Oklahoma Health Sciences Center. It was conducted to shed more light on how many school-age children have ADHD, how the condition develops over time, what other conditions and risks children may experience, and about treatments they may receive. Data were collected to learn more about ADHD in diverse population groups, the quality and patterns of treatment, and the factors that affect short- and long-term outcomes for children.

Project to Learn About Youth – Mental Health

The Project to Learn About Youth – Mental Health (PLAY-MH) expanded the focus to study a range of mental, behavioral, or emotional disorders including ADHD and tic disorders (such as Tourette syndrome)  in four communities. The project provides information that can be used for public health prevention and intervention strategies to support children’s health and development.

Study questions include

• What percentage of children in the community has one or more mental, behavioral, or emotional disorders ?
• How frequently do these disorders appear together?
• What types of treatment are children receiving?

  Top of Page

Understanding Risk

It is not known what causes ADHD. ADHD is often seen in families, and genes appear to play a role, but other factors may contribute or make symptoms worse. For example, some environmental exposures have been linked to increased ADHD symptoms , but the evidence has been inconsistent. Knowing more about those factors would help with planning how to decrease the risk for ADHD. NCBDDD funded a comprehensive literature review of studies that investigate a large range of factors that might increase the risk for ADHD. The results will increase the ability of public health professionals to make the most informed decisions and recommendations about potential public health prevention strategies.

Public health issues in ADHD can be divided into three areas:

• Understanding how many children have ADHD and whether they are properly diagnosed.
• Understanding and addressing the impact of ADHD in the population.
• Understanding which treatments are effective and which are best for children of different ages and in different communities.

Key public health questions yet to be answered include

• What are the causes, and the factors that increase the risk or severity of ADHD?
• How many children have ADHD? Is the rate increasing?
• How many children have ADHD and other conditions at the same time?
• What social and economic impacts does ADHD have on families, schools, the workforce, and the judicial and health systems?
• Are ADHD and other co-occurring conditions  being appropriately diagnosed and treated?
• Are people with ADHD able to access appropriate and timely treatment?
• How effective are the treatments and what are their long-term effects?

Previous Workshop Summaries

• Epidemiologic Issues in ADHD Workshop (April 14, 1999)
• Public Health Issues in ADHD: Individual, System, and Cost Burden of the Disorder (May, 17, 1999)
• ADHD Long-term Outcomes: Comorbidity, Secondary Conditions, and Health Risk Behaviors (June 9, 1999)
• Public Health Issues in the Treatment of ADHD Workshop (June 15, 1999)

Birnbaum HG, Kessler RC, Lowe SW, Secnik K, Greenberg PE, Leong SA, et al. Costs of attention deficit-hyperactivity disorder (ADHD) in the US: excess costs of persons with ADHD and their family members in 2000. Current medical research and opinion 2005;21(2):195-206 .

To receive email updates about this topic, enter your email address:

Exit Notification / Disclaimer Policy

• The Centers for Disease Control and Prevention (CDC) cannot attest to the accuracy of a non-federal website.
• Linking to a non-federal website does not constitute an endorsement by CDC or any of its employees of the sponsors or the information and products presented on the website.
• You will be subject to the destination website's privacy policy when you follow the link.
• CDC is not responsible for Section 508 compliance (accessibility) on other federal or private website.

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

• View all journals

ADHD articles from across Nature Portfolio

ADHD – attention deficit hyperactivity disorder – is a neurodevelopmental disorder that involves problems with attention, concentration and/or increased activity levels, resulting in problems with school, work and social situations. Individuals with ADHD also often experience trouble with impulse control.

Latest Research and Reviews

Cortico-striatal differences in the epigenome in attention-deficit/ hyperactivity disorder

• Gauri G. Shastri
• Gustavo Sudre
• Philip Shaw

Maternal diabetes and risk of attention-deficit/hyperactivity disorder in offspring in a multinational cohort of 3.6 million mother–child pairs

In a large multinational cohort study, maternal, gestational or pregestational diabetes was associated with only a small-to-moderate risk of ADHD in offspring, contrary to previous estimates that showed stronger effect sizes, attributing the differences in findings to confounding by shared genetic and familial factors.

• Adrienne Y. L. Chan
• Ian C. K. Wong

Tau pathology is associated with synaptic density and longitudinal synaptic loss in Alzheimer’s disease

Transcranial random noise stimulation (tRNS) improves hot and cold executive functions in children with attention deficit-hyperactivity disorder (ADHD)

• Vahid Nejati
• Mahshid Dehghan
• Michael A. Nitsche

Discontinuation of psychotropic medication: a synthesis of evidence across medication classes

• Christiaan H. Vinkers
• Ralph W. Kupka
• Jurjen J. Luykx

Individualized atomoxetine response and tolerability in children with ADHD receiving different dosage regimens: the need for CYP2D6 genotyping and therapeutic drug monitoring to dance together

• Hong-Li Guo

News and Comment

Gestational epigenetic age and ADHD symptoms in childhood: a prospective, multi-cohort study

• Kristina Salontaji
• Kristine L. Haftorn
• Charlotte A. M. Cecil

Connecting clinical and genetic heterogeneity in ADHD

Understanding clinical heterogeneity in attention deficit hyperactivity disorder (ADHD) is important for improving personalized care and long-term outcomes. A study exploits the large scale and breadth of phenotyping of the iPSYCH cohort to link clinical heterogeneity to genetic heterogeneity in ADHD.

• Chloe X. Yap
• Jacob Gratten

Treatment dilemmas in childhood ADHD

Stimulants and α 2 -adrenergic agonists both improve symptoms of ADHD in preschool-age children, but they have different side effects.

• Karen O’Leary

Leveraging aggression risk gene expression in the developing and adult human brain to guide future precision interventions

• Sarah L. Rader
• Alan S. Lewis

Molecular Psychiatry , August 2020: new impact factor, and highlights of recent advances in psychiatry, including an overview of the brain’s response to stress during infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

• Julio Licinio

Polycystic ovarian syndrome and autism spectrum disorder in the offspring: Should the primary outcome have been different?

• Vikas Menon
• Chittaranjan Andrade
• Kandavel Thennarasu

Quick links

• Explore articles by subject
• Guide to authors
• Editorial policies

Celebrating 25 Years

• Join ADDitude
•  | 

• What Is ADHD?
• The ADHD Brain
• ADHD Symptoms
• ADHD in Children
• ADHD in Adults
• ADHD in Women
• Find ADHD Specialists
• New! Symptom Checker
• ADHD Symptom Tests
• All Symptom Tests
• More in Mental Health
• Medication Reviews
• ADHD Medications
• Natural Remedies
• ADHD Therapies
• Managing Treatment
• Treating Your Child
• Behavior & Discipline
• School & Learning
• Teens with ADHD
• Positive Parenting
• Schedules & Routines
• Organizing Your Child
• Health & Nutrition
• More on ADHD Parenting
• Do I Have ADD?
• Getting Things Done
• Relationships
• Time & Productivity
• Organization
• Health & Nutrition
• More for ADHD Adults
• Free Webinars
• Free Downloads
• ADHD Videos
• ADHD Directory
• eBooks + More
• Newsletters
• Guest Blogs
• News & Research
• For Clinicians
• For Educators
• Manage My Subscription
• Get Back Issues
• Digital Magazine
• Gift Subscription
• Renew My Subscription
• ADHD & Symptom Tests

Face It — People with ADHD Are Wired Differently

The more we “see” the adhd brain with neuroimaging, the more we understand how it works. read this in-depth breakdown to learn about the latest discoveries and the most current research on the adhd brain..

“Our HVAC system seems overactive,” I explained later to my husband. “Could it be too big for the office space?”

“It’s probably the thermostat, not the air-conditioner,” he said. His insight didn’t warm my office, but it made sense. It wasn’t a cooling-system problem, but a control-system problem. Punching temperature control buttons wasn’t helpful if the instructions weren’t getting to the air-conditioner.

A few days later, I met an office neighbor. When I told him about my problem, he proposed another theory: “Your thermostat doesn’t work. My thermostat controls your air conditioner. We aren’t really sure if it controls my offices. No matter how much I lower it, we’re always too hot.” A little more investigation revealed that his thermostat didn’t control my office, and that no one — not even the building’s owners — understood the wiring.

Understanding how ADHD brains are wired is critical for understanding how to explain and treat the disorder. For decades, we weren’t sure how ADHD brains worked, and this led to many misunderstandings about the syndrome. Many doctors, therapists, social workers, and coaches tried to teach children with attention deficit disorder ( ADHD or ADD ) to slow down using the self-control methods that neurotypical children use. They thought they were programming the right thermostat.

[ Free Download: Secrets of the ADHD Brain ]

“Take a deep breath and press the following buttons on your activity thermostat” makes sense if the wiring is standard, but not if the wires are connected differently, as they are in children and adults with ADHD. The most current research on brain imaging is starting to let us trace the wiring, so we can untangle the misconceptions that experts, as well as those with ADHD, have about the disorder and the brain. Our new understanding of the brain promises to change the way we treat ADHD.

The Brain Up Close

Researchers use structural imaging, which provides two- or three-dimensional pictures, to uncover the anatomy of the brain. Computed tomography (CT) scans and magnetic resonance imaging (MRI) are examples of structural imaging techniques. The images are used to measure the size and volume of the whole brain or specific areas within the brain.

To study brain functions, researchers use scans that show physiologic activity inside the brain. You’ve probably seen these studies covered in the press. The coverage usually includes statements like “X is the part of the brain that ‘lights up’ when people do Y.” Older functional scans — electroencephalography (EEG) and single-photon emission computed tomography (SPECT) — measure patterns of nerve activity or blood flow, respectively. Newer methods, such as positron emission tomography (PET), use radioactive tracers that can be seen in the brain.

Much of what we know about dopamine function in the brain results from the radioactive tracer raclopride, which is injected into the body and attaches to empty dopamine receptors. Raclopride binding is higher in the brains of children or adults with ADHD, so we “see” that their dopamine activity levels are low. Raclopride binding drops to normal levels an hour after stimulant medications are taken. This is why neuroscientists now say that stimulants normalize dopamine function in the brains of people with ADHD.

[ Neuroimaging and ADHD: Findings, Limitations, and Promise ]

Functional imaging gives information about activity in specific areas of subjects’ brains before and during task performance. Functional magnetic resonance imaging (fMRI) shows oxygen uptake in areas of high nerve activity, and magnetoencephalography (MEG) shows us nerve activity in detail. A promising variant of fMRI, called fMRI-DTI (for diffusion tensor imaging), measures the connection between different regions of the brain. Crosstalk — the ability of different regions of the brain to communicate with each other — is vital to brain function, and it is significantly reduced in ADHD brains.

Many different techniques are used in brain imaging — though not all provide valid or generalizable information — and they give researchers useful glimpses into brain wiring and structure. In order to understand the causes of ADHD better and to treat it more effectively, we need to know the wiring of the brain and how it operates.

The ADHD Brain: Structurally Different

Neuroimaging studies have revealed the structural differences in the ADHD brain. Several studies have pointed to a smaller prefrontal cortex and basal ganglia, and decreased volume of the posterior inferior vermis of the cerebellum — all of which play important roles in focus and attention.

What this means is ADHD is not a difference in behavioral preference. Instead, ADHD appears to be partially attributed to a difference in how the brain is structured. What may look like behavioral choices — laziness, sloppiness, and forgetfulness — are likely due to differences in brain structure.

Researchers at Cambridge, England, and Oulu, Finland, followed 49 adolescents diagnosed with ADHD at age 16 and examined their brain structure and memory function in young adulthood (between 20 to 24 years old), compared to a control group of 34 young adults. The results showed that the group diagnosed in adolescence had reduced brain volume as adults, leading to poorer memory function, even if they no longer met the diagnostic checklist criteria for ADHD. Researchers saw reduced gray matter in a region deep within the brain known as the caudate nucleus, the brain region that integrates information across different parts of the brain and supports cognitive functions, including memory.

Because the structural differences persist into adulthood for most children with ADHD, the chance that a child will outgrow ADHD is not as great as we once thought. Sixty to 75 percent of adults who had ADHD in childhood continue to meet diagnostic criteria in adulthood. Most of those who “outgrow” ADHD continue to manifest many of its symptoms. Adults may score just under the cutoff on diagnostic checklists, but they are likely to continue to have abnormal brain structure, as well as functional impairments in relationships and the workplace.

The Changing Brain

Researchers once thought that each human function was assigned to a specific part of the brain, and that a part damaged by trauma or disease permanently lost its function. Now, research has shown that the human brain changes in response to stimulation; brains have neuroplasticity. The good news is that your brain retains this ability to change from birth to old age. ADHD brains that have deficits in one area will attempt to rewire themselves to accomplish a task.

There are activities that can increase the brain’s effectiveness. Meditation, for example, changes the brain in important ways. Researchers worked with people who’d never meditated before (ADHD was not accounted for as a variable), and put one group through an eight-week mindfulness-based stress-reduction program. The primary difference was in the posterior cingulate, which is involved in mind wandering and self-awareness. Another notable change was in the left hippocampus, which assists in learning, cognition, memory, and emotional regulation. Subsequent studies applied this research using ADHD participants, and similar changes were noticed.

The ADHD Brain: A Network of Its Own

Researchers at Harvard University studied ADHD and non-ADHD subjects as they responded to a challenging cognitive task. While both groups had difficulty with the task, the ADHD group failed to activate their anterior cingulate cortex, which plays two significant roles in attentional processing: adjusting the focus of a person’s attention (where and when) as well as balancing the focus of attention (how much attention for how long). ADHD participants engaged a different, less specialized part of their brain when tackling the task.

What this means. This research highlights what individuals with attention deficit already know. It is difficult to know what to do and when to do it. This is because of an apparent lack of ability to engage the most effective part of their brain, the anterior cingulate cortex.

The default mode network (DMN) represents the regions of the brain that are active when no specific task is being performed — while daydreaming, say, an activity that is undervalued by researchers and society. In the past, this was called the “resting state.” Once functional scans showed how active the brain is at rest, the name was changed.

The DMN takes care of task-irrelevant mental processes, mind-wandering, contemplation, and reflection. It comprises the precuneus/posterior cingulate cortex, the medial prefrontal cortex, and the lateral and inferior parietal cortex. The DMN is more active when individuals are at wakeful rest, engaged in internal tasks, such as daydreaming, recovering memories, and assessing others’ perspectives. Conversely, when individuals work on active, willful, goal-directed tasks, the DMN deactivates, and attentional pathways engage. The DMN and cognitive control networks work in opposing directions to accommodate attentional demands.

In ADHD, the daydreaming brain doesn’t quiet down when the attention circuits turn on. Several studies have focused on the connectivity of the DMN in individuals with ADHD. Weak connections between control centers and the DMN cause an inability to modulate DMN activity. Many studies of children, adolescents, and adults with ADHD, taking and not taking medication, have found that the balance between the cognitive control network and the DMN is either reduced, or absent, in those with ADHD.

The lack of separation between the cognitive control network and the DMN in the ADHD brain suggests why there are attentional lapses. People with ADHD can instruct their focus control system to pay attention to the task at hand — say a pile of bills that need to be paid — but the circuits that connect to the DMN fail to send the instructions to quiet down. When the DMN notices a new magazine lying next to the pile of bills, emotional interest centers light up and overwhelm the weak voice of the cognitive centers.

We have come a long way from our earliest concepts of ADHD as hyperactivity to a dysfunction in the control pathways, but much remains to be studied. Finding which therapies strengthen control centers, which ones improve communication between control centers and action centers, and which ones bypass typical pathways will help adults with the disorder become more productive and confident.

Treating ADHD: What Really Works Best?

“Just tell me one thing so I can get this straight: How much of treating ADHD is medications, and how much is everything else? Is it 50-50? 80-20? Give me a number, so I can wrap my mind around it.” Alex wanted Oren Mason, M.D., a family physician in Grand Rapids, Michigan, to cut to the chase. Alex’s ADHD treatment plan was complex. He was overwhelmed by the recommendations to exercise daily, hire a coach, listen to some ADHD audio books, get more sleep, and start some supplements. The idea of medication sounded promising to him, but the trials needed to find the right dose of the right medication could take months.

“How much bang for the buck do these treatments give?” is a fair question. People with ADHD have already tried dozens of strategies to improve attention and efficiency that, over time, fizzled out.

On one hand, if non-medication therapies were going to successfully treat Alex’s ADHD, they would have done that. He had worked with tutors, therapists, and nutritionist, and read self-help books, but he still had inattention and self-control issues. Medication response can be remarkable, but it isn’t the whole story. Physicians can’t prescribe pills and assume a patient’s ADHD will get better.

Many doctors lack personal experience with ADHD, and don’t understand how much more rigorous the treatment is than the oft-heard “just pop a pill.” Investigators define successful treatment in scientifically accurate terms such as “a 40 percent or better reduction of investigator-rated DSM-V symptomatology, along with a CGI-I score of at least +2.”

Patients, bless them, don’t talk like that. They tend to have goals for successful treatment, such as “get more organized,” “study,” “work to my potential,” and “be more thoughtful” or “be less frustrated with my children.” These goals are hard to express in numbers. They have an “It’s hard to describe, but I’ll know it when I see it” endpoint.

Alex wasn’t asking Dr. Mason to quote studies, just to help him reach some of his goals. Dr. Mason was about to say “50-50,” to emphasize that the effects of medication and non-medication therapies are both important, but what came out was, “They’re both essential. It’s 100-100. Neither of them matters much without the other.”

Researchers have worked on that question and have tried to give us more accurate numbers, even if they aren’t exact. It turns out that you get about 30 percent of what researchers call “the potential response” with medications alone, and about the same from evidence-based non-medication therapies. Using only one therapy alone misses 70 percent of the potential improvement. In other words, if your ADHD were a pie, one evidence-based therapy would eat about one third of it. Use another therapy and 30 percent more would be gone, and so on.

Which is best: medication or the non-medication therapies ? The answer is not the scientifically accurate one, but the one that spilled out intuitively that day: 100-100. The best responses come with both therapies done at full-court-press levels.

[ Free Resource: Stimulant Medications Chart for the Treatment of ADHD ]

What Causes ADHD?: Read These Next

Is ADHD Genetic? Yes and No

Why ADD Makes You Feel. So. Much.

Exaggerated Emotions: How and Why ADHD Triggers Intense Feelings

3 Types of Sensory Disorders That Look Like ADHD

Adhd newsletter, your mental health & strength training begin here..

It appears JavaScript is disabled in your browser. Please enable JavaScript and refresh the page in order to complete this form.

Secrets of the ADHD Brain

Research has demonstrated that ADHD has a very strong neurobiological basis.

Although precise causes have not yet been identified, there is little question that heredity makes the largest contribution to the expression of the disorder in the population.

In instances where heredity does not seem to be a factor, difficulties during pregnancy, prenatal exposure to alcohol and tobacco, premature delivery, significantly low birth weight, excessively high body lead levels, and postnatal injury to the prefrontal regions of the brain have all been found to contribute to the risk for ADHD to varying degrees.

Research does not support the popularly held views that ADHD arises from excessive sugar intake, excessive television viewing, poor child management by parents, or social and environmental factors such as poverty or family chaos. Of course, many things, including these, might aggravate symptoms, especially in certain individuals.  But the evidence for such individual aggravating circumstances is not strong enough to conclude that they are primary causes of ADHD.  A related problem that has some accumulating evidence is sensitivity to food or additives such as colorings and preservatives.  Several controlled double-blind studies suggest that these might be important for a minority of children with ADHD, and a couple of controlled studies suggest a small effect on all children whether or not they have ADHD.  Further research on this connection is warranted.

Neurochemistry

Structural and functional imaging research on the neurochemistry of ADHD implicates the catecholamine-rich frontal-subcortical systems in the pathophysiology of ADHD. The effectiveness of stimulant medication, along with animal models of hyperactivity, also point to catecholamine disruption as at least one source of ADHD brain dysfunction.

Basic neuroimaging research is being conducted to further delineate the pathophysiology of ADHD, determine diagnostic utility of neuroimaging, and elucidate the physiological effects of treatment.  However, the research is not definitive enough for practical application of neuroimaging.

Executive Function

Many of the symptoms classified as ADHD symptoms of inattention are actually symptoms of executive function impairments. Executive function refers to a wide range of central control processes in the brain that activate, integrate, and manage other brain functions.

Best put, Thomas E. Brown, Ph.D., of Yale University compares executive function to the conductor of an orchestra.  The conductor organizes, activates, focuses, integrates, and directs the musicians as they play, enabling the orchestra to produce complex music. Similarly, the brain’s executive functions organize, activate, focus, integrate and direct, allowing the brain to perform both routine and creative work.

The components of executive functioning that impact school or work:

• working memory and recall (holding facts in mind while manipulating information; accessing facts stored in long-term memory)
• activation, arousal and effort (getting started; paying attention; completing work)
• emotion control (tolerating frustration; thinking before acting or speaking)
• internalizing language (using self-talk to control one’s behavior and direct future actions)
• complex problem solving (taking an issue apart, analyzing the pieces, reconstituting and organizing them into new ideas)

Below is research on the science of ADHD as a real disorder.

American Medical Association (AMA)

Diagnosis and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents, April 1998 Citation: Journal of the American Medical Association 279(14): 1100-1107, 1998

ADHD “is a commonly seen neuropsychiatric syndrome that has been extensively studied over the past four decades . . . It should be noted that debate over ADHD within the research and medical communities has been mild and mostly concerned with nuances in the diagnosis and treatment paradigms. By contrast, highly inflammatory public relations campaigns and pitched legal battles have been waged (particularly by groups such as the Church of Scientology) that seek to label the whole idea of ADHD as an illness a “myth” . . . It is thus most important to separate legitimate concerns raised by scientific papers from abstract, distorted, or mendacious information from other sources.”

Surgeon General of the United States

Mental Health: A Report of the Surgeon General, December 1999 Full Text

Chapter Three (Children and Mental Health), Section Four is devoted entirely to the science of ADHD. “ADHD, which is the most commonly diagnosed behavioral disorder of childhood, occurs in 3 to 5 percent of school-age children . . . The exact etiology of ADHD is unknown, although neurotransmitter deficits, genetics, and perinatal complications have been implicated . . . The dopamine hypothesis has thus driven much of the recent research into the causes of ADHD.”

National Institutes of Health (NIH)

National Institute of Mental Health Multimodal Treatment Study of Children with ADHD, December 1999 Citation: Archives of General Psychiatry 56(12): 1073-86, 1999

This landmark study is “the first major clinical trial to look at childhood mental illness and the largest NIMH clinical trial to date.”

Diagnosis and Treatment of Attention-Deficit Hyperactivity Disorder: Consensus Development Conference Statement, November 1998 Citation: NIH Consensus Statement 16(2): 1-37, 1998 Full Text

ADHD “is a commonly diagnosed behavioral disorder of childhood that represents a costly major public health problem . . .”

National Institute of Mental Health (NIMH)

Attention Deficit Hyperactivity Disorder (ADHD) Rev. 2013

“Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood disorders and can continue through adolescence and adulthood. Symptoms include difficulty staying focused and paying attention, difficulty controlling behavior, and hyperactivity (over-activity).”

Centers for Disease Control and Prevention (CDC)

Attention Deficit Disorder and Learning Disability: United States, 1997-98, May 2002 Citation: Vital Health Statistics 10(206), 2002 Full Text

This report demonstrates “that ADD and LD [learning disabilities] are among the most common chronic conditions affecting school-aged children in the United States.”

2002 International Consensus Statement on ADHD

Citation: Clinical Child and Family Psychology Review 5(2): 89-111, 2002

Roughly 100 scientists from the international community created the consensus statement as a reference on the status of the scientific findings concerning this disorder. “As a matter of science, the notion that ADHD does not exist is simply wrong. All of the major medical associations and government health agencies recognize ADHD as a genuine disorder because the scientific evidence indicating it is so overwhelming.”

American Academy of Pediatrics (AAP)

Clinical Practice Guideline: Treatment of the School-Aged Child with Attention-Deficit/Hyperactivity Disorder, October 2001 Citation: Pediatrics 108(4): 1033-44, 2001

This guideline “is based on an extensive review of the medical, psychological, and educational literature” and “emphasizes consideration of ADHD as a chronic condition.”

Clinical Practice Guideline: Diagnosis and Evaluation of the Child with Attention-Deficit/Hyperactivity Disorder, May 2000 Citation: Pediatrics 105 (5): 1158-70, 2000

“Attention-Deficit/Hyperactivity Disorder (ADHD) is the most common neurobehavioral disorder of childhood.”

American Academy of Child and Adolescent Psychiatry (AACAP)

Practice Parameters for the Assessment and Treatment of Children and Adolescents with Attention-Deficit/Hyperactivity Disorder American Academy of Child and Adolescent Psychiatry In Press, 2007

“Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most common psychiatric disorders of childhood and adolescence.”

Practice Parameter for the Use of Stimulant Medications in the Treatment of Children, Adolescents, and Adults, June 2001 Citation: Journal of the American Academy of Child and Adolescent Psychiatry 41(2 Suppl): 26S-49S, 2002

“Long thought of as a childhood disorder, ADHD is now known to persist into adolescence and adulthood.”

Mayo Clinic, Rochester, Minnesota

Utilization and Costs of Medical Care for Children and Adolescents with and without Attention-Deficit/Hyperactivity Disorder, January 2001 Citation: Journal of the American Medical Association 285(1): 60-6, 2001

“Attention-Deficit/Hyperactivity Disorder (ADHD) is a relatively common behavioral disorder of childhood, with important consequences for affected individuals, their families, and society.”

How Common Is Attention-Deficit/Hyperactivity Disorder?, March 2002

Citation: Archives of Pediatrics and Adolescent Medicine 156(3): 209-10, 2002 Summary

According to Mayo researchers, this study is the largest population-based study of the occurrence of ADHD to date and “it indicates that this disorder is commonly seen in children between the ages 5 and 19 years.”

Other Web Sites:

• CDC and ADHD Research Information on CDC’s current research efforts, activities, and research agenda.
• Participating in Research (ClinicalTrials.Gov) ClinicalTrials.gov provides regularly updated information about federally and privately supported clinical research in human volunteers. ClinicalTrials.gov gives you information about a trial’s purpose, who may participate, locations, and phone numbers for more details. Before searching, you may want to learn more about clinical trials.
• NIMH Clinical Trials on ADHD These NIMH-funded studies are currently recruiting study participants.
• Visit the NRC on Social Media

The information provided by CHADD’s National Resource Center on ADHD is supported by Cooperative Agreement Number NU38DD000002 funded by the Centers for Disease Control and Prevention (CDC). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the CDC or the Department of Health and Human Services (HHS).

Recent Webinars

• Questions & Answers – The Essential Elements that Guide Therapeutic Work within Latino Immigrant Families Ask The Expert
• Presentation – The Essential Elements that Guide Therapeutic Work within Latino Immigrant Families Ask The Expert
• Why A Mindfulness Reset Is So Powerful For Dealing With Resistant Or Adverse Behaviors Ask The Expert

Other Resources

• ADHD Fact Sheets
• Listen to Our Podcasts
• Online Communities
• ADHD Information Library
• Adult to Adult Training
• Teacher to Teacher Training
• Parent to Parent Training
• Upcoming Events

Subscribe to our mailing list

Advertisement

“Being ADHD”: a Qualitative Study

• ORIGINAL PAPER
• Published: 20 January 2022
• Volume 6 , pages 20–28, ( 2022 )

Cite this article

• Rosalind Redshaw   ORCID: orcid.org/0000-0002-4965-4000 1 &
• Lynne McCormack 1  

2787 Accesses

6 Citations

Explore all metrics

Attention deficit hyperactivity disorder (ADHD) is well recognised as a persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development; however, little is known about the subjective experience of “being ADHD”. This phenomenological idiographic study explored how nine individuals with ADHD make sense of their life experiences, ability to function, and ideas about self in the context of ADHD.

Semi-structured interviews were used to collect data from nine participants aged 29 to 54. Audio recordings of interviews were then transcribed and analysed according to the protocols of interpretative phenomenological analysis (IPA).

Three themes emerged (1) otherness; (2) pixies, monkeys, and living in the moment; and (3) Challenging “broken”. Themes encompass the experience of being different to others, mechanics of daily functioning, and advantages of being ADHD.

A tendency to live in the moment was consistent across the nine participants in this study and aligns with quantitative research showing differences in the processing of temporal information in ADHD. The effects of this tendency on day-to-day functioning are linked to typical symptoms of ADHD, as well as perceived advantages. Participants attributed an uncommon degree of energy, optimism, adventurousness and curiosity, and novel problem-solving ability to their ADHD, adding to existing literature that suggests there are advantages to this unique mental architecture. Identifying positive aspects to ADHD offers clinicians and educators a pathway for mitigating the negative effects on self that flow from the challenges of ADHD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price includes VAT (Russian Federation)

Instant access to the full article PDF.

Rent this article via DeepDyve

Institutional subscriptions

Similar content being viewed by others

The positive aspects of attention deficit hyperactivity disorder: a qualitative investigation of successful adults with ADHD

Jane Ann Sedgwick, Andrew Merwood & Philip Asherson

Experienced consequences of being diagnosed with ADHD as an adult – a qualitative study

Sara Lina Hansson Halleröd, Henrik Anckarsäter, … Marianne Hansson Scherman

Attention Deficit Hyperactivity Disorder: Third-Wave Behavior Therapy Conceptualization

American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5 th ed.). https://doi.org/10.1176/appi.books.9780890425596 .

Barkley, R. A. (1997). Attention-deficit/hyperactivity disorder, self-regulation, and time: Toward a more comprehensive theory. Journal of Developmental and Behavioral Pediatrics, 18 , 271–279. https://doi.org/10.1097/00004703-199708000-00009

Article   PubMed   Google Scholar  

Bubic, A., Von Cramon, D. Y., & Schubotz, R. I. (2010). Prediction, cognition and the brain. Frontiers in Human Neuroscience, 4 , 25. https://doi.org/10.3389/fnhum.2010.00025

Article   PubMed   PubMed Central   Google Scholar  

Castellanos, F. X., Sonuga-Barke, E. J., Milham, M. P., & Tannock, R. (2006). Characterizing cognition in ADHD: Beyond executive dysfunction. Trends in Cognitive Sciences, 10 (3), 117–123. https://doi.org/10.1016/j.tics.2006.01.011

Caye, A., Spadini, A. V., Karam, R. G., Grevet, E. H., Rovaris, D. L., Bau, C. H., Rohde, L. A., & Kieling, C. (2016). Predictors of persistence of ADHD into adulthood: A systematic review of the literature and meta-analysis. European Child & Adolescent Psychiatry , 25 (11), 1151–1159. https://doi.org/10.1007/s00787-016-0831-8 .

Cortese, S., Adamo, N., Del Giovane, C., Mohr-Jensen, C., Hayes, A. J., Carucci, S., ..., & Hollis, C. (2018). Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: A systematic review and network meta-analysis. The Lancet Psychiatry , 5 (9), 727-738. https://doi.org/10.1016/s2215-0366(18)30269-4 .

de Schipper, E., Mahdi, S., Coghill, D., de Vries, P. J., Gau, S. S. F., Granlund, M., & Rohde, L. (2015). Towards an ICF core set for ADHD: A worldwide expert survey on ability and disability. European Child & Adolescent Psychiatry, 24 (12), 1509–1521.

Article   Google Scholar  

Douglas, V. I., & Parry, P. A. (1994). Effects of reward and nonreward on frustration and attention in attention deficit disorder. Journal of Abnormal Child Psychology, 22 (3), 281–302. https://doi.org/10.1007/bf02168075

Gawrilow, C., Merkt, J., Goossens-Merkt, H., Bodenburg, S., & Wendt, M. (2011). Multitasking in adults with ADHD. ADHD Attention Deficit and Hyperactivity Disorders, 3 (3), 253–264. https://doi.org/10.1007/s12402-011-0056-0

Graziano, M. S., & Webb, T. W. (2015). The attention schema theory: A mechanistic account of subjective awareness. Frontiers in Psychology, 6 , 500. https://doi.org/10.3389/fpsyg.2015.00500

Graziano, P. A., Garcia, A. M., & Landis, T. D. (2020). To fidget or not to fidget, that is the question: A systematic classroom evaluation of fidget spinners among young children with ADHD. Journal of Attention Disorders, 24 (1), 163–171.

Griffiths, D. (2017). Neurodiversity: An idea whose time has come? Assessment & Development Matters, 9 (4), 16–19.

Google Scholar  

Kasparek, T., Theiner, P., & Filova, A. (2015). Neurobiology of ADHD from childhood to adulthood: Findings of imaging methods. Journal of Attention Disorders, 19 (11), 931–943. https://doi.org/10.1177/1087054713505322

Krueger, M., & Kendall, J. (2001). Descriptions of self: An exploratory study of adolescents with ADHD. Journal of Child and Adolescent Psychiatric Nursing, 14 (2), 61–72. https://doi.org/10.1111/j.1744-6171.2001.tb00294.x

Mahdi, S., Viljoen, M., Massuti, R., Selb, M., Almodayfer, O., Karande, S., de Vries, P. J., Rohde, L., & Bölte, S. (2017). An international qualitative study of ability and disability in ADHD using the WHO-ICF framework. European Child & Adolescent Psychiatry , 26 (10), 1219–1231. https://doi.org/10.1007/s00787-017-0983-1 .

Marco, R., Miranda, A., Schlotz, W., Melia, A., Mulligan, A., Müller, U., ..., & Medad, S. (2009). Delay and reward choice in ADHD: An experimental test of the role of delay aversion. Neuropsychology , 23 (3), 367. https://doi.org/10.1037/a0014914 .

Molitor, S. J., & Langberg, J. M. (2017). Using task performance to inform treatment planning for youth with ADHD: A systematic review. Clinical Psychology Review, 58 , 157–173. https://doi.org/10.1016/j.cpr.2017.10.007

Nagel, T. (1974). What is it like to be a bat? The Philosophical Review, 83 (4), 435–450. https://doi.org/10.2307/2183914

Noreika, V., Falter, C. M., & Rubia, K. (2013). Timing deficits in attention-deficit/hyperactivity disorder (ADHD): Evidence from neurocognitive and neuroimaging studies. Neuropsychologia, 51 (2), 235–266. https://doi.org/10.1016/j.neuropsychologia.2012.09.036

Redish, A. D. (2013). The mind within the brain: How we make decisions and how those decisions go wrong . Oxford University Press.

Sagvolden, T., Johansen, E. B., Aase, H., & Russell, V. A. (2005). A dynamic developmental theory of attention-deficit/hyperactivity disorder (ADHD) predominantly hyperactive/impulsive and combined subtypes. Behavioral and Brain Sciences, 28 (3), 397–418. https://doi.org/10.1017/s0140525x05000075

Sarver, D. E., Rapport, M. D., Kofler, M. J., Raiker, J. S., & Friedman, L. M. (2015). Hyperactivity in attention-deficit/hyperactivity disorder (ADHD): Impairing deficit or compensatory behavior? Journal of Abnormal Child Psychology, 43 (7), 1219–1232. https://doi.org/10.1007/s10802-015-0011-1

Schatz, N. K., Fabiano, G. A., Cunningham, C. E., Waschbusch, D. A., Jerome, S., Lupas, K., & Morris, K. L. (2015). Systematic review of patients’ and parents’ preferences for ADHD treatment options and processes of care. The Patient-Patient-Centered Outcomes Research, 8 (6), 483–497. https://doi.org/10.1007/s40271-015-0112-5

Schimmel, A. (2020). ADHD and fidget spinners: Using fNIRs to detect changes in relative neural efficiency during the Purdue Pegboard Test [Doctoral dissertation, University of Delaware].

Schultz, W. (2007). Multiple dopamine functions at different time courses. Annual Review of Neuroscience, 30 , 259–288.

Sedgwick, J. A., Merwood, A., & Asherson, P. (2018). The positive aspects of attention deficit hyperactivity disorder: A qualitative investigation of successful adults with ADHD. ADHD Attention Deficit and Hyperactivity Disorders, 11 (3), 241–253. https://doi.org/10.1007/s12402-018-0277-6

Slater, J. L., & Tate, M. C. (2018). Timing deficits in ADHD: Insights from the neuroscience of musical rhythm. Frontiers in Computational Neuroscience, 12 , 51. https://doi.org/10.3389/fncom.2018.00051

Smith, J. A., Flowers, P., & Larkin, M. (2009). Interpretative phenomenological analysis: Theory, method, and research . Sage Publications.

Tarver, J., Daley, D., & Sayal, K. (2014). Attention-deficit hyperactivity disorder (ADHD): An updated review of the essential facts. Child: Care, Health and Development, 40 (6), 762–774. https://doi.org/10.1111/cch.12139

Yardley, L. (2000). Dilemmas in qualitative health research. Psychology and Health, 15 (2), 215–228.

Download references

Acknowledgements

We are extremely grateful to the participants who took part in this research for their time and efforts.

Author information

Authors and affiliations.

School of Psychological Sciences, College of Engineering, Science & Environment, University of Newcastle, NSW, 2308, Callaghan, Australia

Rosalind Redshaw & Lynne McCormack

You can also search for this author in PubMed   Google Scholar

Contributions

RR: designed and executed the study, independently and jointly analysed the data, and wrote the paper. LM: trained RR in IPA, independently and jointly analysed the data, and collaborated with the design and writing of the study and editing of the final manuscript.

Corresponding author

Correspondence to Rosalind Redshaw .

Ethics declarations

Ethics statement.

This research was approved by the University of Newcastle Australia Human Research Ethics Committee. All procedures involving human participants were in accordance with the ethical standards of the University of Newcastle Australia Human Research Ethics Committee.

Informed Consent Statement

All participants provided informed consent prior to and following their participation in the study.

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher's note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Redshaw, R., McCormack, L. “Being ADHD”: a Qualitative Study. Adv Neurodev Disord 6 , 20–28 (2022). https://doi.org/10.1007/s41252-021-00227-5

Download citation

Accepted : 08 November 2021

Published : 20 January 2022

Issue Date : March 2022

DOI : https://doi.org/10.1007/s41252-021-00227-5

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• Qualitative study
• Living in the moment
• Advantages of ADHD
• Timing in ADHD
• Neurodiversity
• Find a journal
• Publish with us
• Track your research

ADHD Research Lab

The ADHD research lab conducts research on Attention Deficit Hyperactivity Disorder with a particular focus on adults with the condition, who are often under-represented in research. Around 3% of adults worldwide have ADHD and there are relatively fewer treatment options available to them compared to children with the condition.

Our research aims to improve our understanding of the condition and support better treatment or management of ADHD symptoms. We largely focus on non-drug treatments, either alone or in combination with the existing approved medications (e.g., stimulant, and non-stimulant drugs). We are currently researching the following:

• Cardio and non-cardio exercise as standalone or adjunct treatments (funded by the Rosetrees Trust)
• Self-management through exercise
• Dietary modulation in the form of protein supplementation with tryptophan
• Eye movement training
• Mindfulness based practice

In addition to these intervention approaches we also explore what the compulsivity in ADHD and whether this has links to the increased risk of substance and behavioural addictions found in the ADHD. All of our studies are listed here: https://www.adhdresearchlab.com/adhd-studies.html . We are also on Twitter and Instagram (@ADHDResearchLab).

Finally, being based in a university, we are interested in what ADHD means for students during their university journey. As such we are conducting research into how individuals with ADHD (as well as other conditions under the umbrella term of neurodiversity) experience online learning and the strategies they develop to be successful in higher education.

Professor Ellie Dommett PhD

Professor of Neuroscience

Related departments

• Department of Psychology
• School of Mental Health & Psychological Sciences
• Institute of Psychiatry, Psychology & Neuroscience

Featured Clinical Reviews

• Screening for Atrial Fibrillation: US Preventive Services Task Force Recommendation Statement JAMA Recommendation Statement January 25, 2022
• Evaluating the Patient With a Pulmonary Nodule: A Review JAMA Review January 18, 2022
• Download PDF
• CME & MOC
• Share X Facebook Email LinkedIn
• Permissions

Acetaminophen Use During Pregnancy and Children’s Risk of Autism, ADHD, and Intellectual Disability

• 1 Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden
• 2 Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
• 3 Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
• 4 Department of Women’s Health, Division of Obstetrics, Karolinska University Hospital, Stockholm, Sweden
• 5 Department of Neonatology, Sachs’ Children and Youth Hospital, Stockholm, Sweden
• 6 Centre for Epidemiology and Community Medicine, Region Stockholm, Stockholm, Sweden
• 7 Department of Epidemiology and Biostatistics, Drexel University Dornsife School of Public Health, Philadelphia, Pennsylvania
• 8 A.J. Drexel Autism Institute, Drexel University, Philadelphia, Pennsylvania

Question   Does acetaminophen use during pregnancy increase children’s risk of neurodevelopmental disorders?

Findings   In this population-based study, models without sibling controls identified marginally increased risks of autism and attention-deficit/hyperactivity disorder (ADHD) associated with acetaminophen use during pregnancy. However, analyses of matched full sibling pairs found no evidence of increased risk of autism (hazard ratio, 0.98), ADHD (hazard ratio, 0.98), or intellectual disability (hazard ratio, 1.01) associated with acetaminophen use.

Meaning   Acetaminophen use during pregnancy was not associated with children’s risk of autism, ADHD, or intellectual disability in sibling control analyses. This suggests that associations observed in other models may have been attributable to confounding.

Importance   Several studies suggest that acetaminophen (paracetamol) use during pregnancy may increase risk of neurodevelopmental disorders in children. If true, this would have substantial implications for management of pain and fever during pregnancy.

Objective   To examine the associations of acetaminophen use during pregnancy with children’s risk of autism, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability.

Design, Setting, and Participants   This nationwide cohort study with sibling control analysis included a population-based sample of 2 480 797 children born in 1995 to 2019 in Sweden, with follow-up through December 31, 2021.

Exposure   Use of acetaminophen during pregnancy prospectively recorded from antenatal and prescription records.

Main Outcomes and Measures   Autism, ADHD, and intellectual disability based on International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes in health registers.

Results   In total, 185 909 children (7.49%) were exposed to acetaminophen during pregnancy. Crude absolute risks at 10 years of age for those not exposed vs those exposed to acetaminophen were 1.33% vs 1.53% for autism, 2.46% vs 2.87% for ADHD, and 0.70% vs 0.82% for intellectual disability. In models without sibling control, ever-use vs no use of acetaminophen during pregnancy was associated with marginally increased risk of autism (hazard ratio [HR], 1.05 [95% CI, 1.02-1.08]; risk difference [RD] at 10 years of age, 0.09% [95% CI, −0.01% to 0.20%]), ADHD (HR, 1.07 [95% CI, 1.05-1.10]; RD, 0.21% [95% CI, 0.08%-0.34%]), and intellectual disability (HR, 1.05 [95% CI, 1.00-1.10]; RD, 0.04% [95% CI, −0.04% to 0.12%]). To address unobserved confounding, matched full sibling pairs were also analyzed. Sibling control analyses found no evidence that acetaminophen use during pregnancy was associated with autism (HR, 0.98 [95% CI, 0.93-1.04]; RD, 0.02% [95% CI, −0.14% to 0.18%]), ADHD (HR, 0.98 [95% CI, 0.94-1.02]; RD, −0.02% [95% CI, −0.21% to 0.15%]), or intellectual disability (HR, 1.01 [95% CI, 0.92-1.10]; RD, 0% [95% CI, −0.10% to 0.13%]). Similarly, there was no evidence of a dose-response pattern in sibling control analyses. For example, for autism, compared with no use of acetaminophen, persons with low (<25th percentile), medium (25th-75th percentile), and high (>75th percentile) mean daily acetaminophen use had HRs of 0.85, 0.96, and 0.88, respectively.

Conclusions and Relevance   Acetaminophen use during pregnancy was not associated with children’s risk of autism, ADHD, or intellectual disability in sibling control analysis. This suggests that associations observed in other models may have been attributable to familial confounding.

Read More About

Ahlqvist VH , Sjöqvist H , Dalman C, et al. Acetaminophen Use During Pregnancy and Children’s Risk of Autism, ADHD, and Intellectual Disability. JAMA. 2024;331(14):1205–1214. doi:10.1001/jama.2024.3172

Manage citations:

© 2024

Artificial Intelligence Resource Center

Cardiology in JAMA : Read the Latest

Browse and subscribe to JAMA Network podcasts!

Others Also Liked

Select your interests.

Customize your JAMA Network experience by selecting one or more topics from the list below.

• Academic Medicine
• Acid Base, Electrolytes, Fluids
• Allergy and Clinical Immunology
• American Indian or Alaska Natives
• Anesthesiology
• Anticoagulation
• Art and Images in Psychiatry
• Artificial Intelligence
• Assisted Reproduction
• Bleeding and Transfusion
• Caring for the Critically Ill Patient
• Challenges in Clinical Electrocardiography
• Climate and Health
• Climate Change
• Clinical Challenge
• Clinical Decision Support
• Clinical Implications of Basic Neuroscience
• Clinical Pharmacy and Pharmacology
• Complementary and Alternative Medicine
• Consensus Statements
• Coronavirus (COVID-19)
• Critical Care Medicine
• Cultural Competency
• Dental Medicine
• Dermatology
• Diabetes and Endocrinology
• Diagnostic Test Interpretation
• Drug Development
• Electronic Health Records
• Emergency Medicine
• End of Life, Hospice, Palliative Care
• Environmental Health
• Equity, Diversity, and Inclusion
• Facial Plastic Surgery
• Gastroenterology and Hepatology
• Genetics and Genomics
• Genomics and Precision Health
• Global Health
• Guide to Statistics and Methods
• Hair Disorders
• Health Care Delivery Models
• Health Care Economics, Insurance, Payment
• Health Care Quality
• Health Care Reform
• Health Care Safety
• Health Care Workforce
• Health Disparities
• Health Inequities
• Health Policy
• Health Systems Science
• History of Medicine
• Hypertension
• Images in Neurology
• Implementation Science
• Infectious Diseases
• Innovations in Health Care Delivery
• JAMA Infographic
• Law and Medicine
• Leading Change
• Less is More
• LGBTQIA Medicine
• Lifestyle Behaviors
• Medical Coding
• Medical Devices and Equipment
• Medical Education
• Medical Education and Training
• Medical Journals and Publishing
• Mobile Health and Telemedicine
• Narrative Medicine
• Neuroscience and Psychiatry
• Notable Notes
• Nutrition, Obesity, Exercise
• Obstetrics and Gynecology
• Occupational Health
• Ophthalmology
• Orthopedics
• Otolaryngology
• Pain Medicine
• Palliative Care
• Pathology and Laboratory Medicine
• Patient Care
• Patient Information
• Performance Improvement
• Performance Measures
• Perioperative Care and Consultation
• Pharmacoeconomics
• Pharmacoepidemiology
• Pharmacogenetics
• Pharmacy and Clinical Pharmacology
• Physical Medicine and Rehabilitation
• Physical Therapy
• Physician Leadership
• Population Health
• Primary Care
• Professional Well-being
• Professionalism
• Psychiatry and Behavioral Health
• Public Health
• Pulmonary Medicine
• Regulatory Agencies
• Reproductive Health
• Research, Methods, Statistics
• Resuscitation
• Rheumatology
• Risk Management
• Scientific Discovery and the Future of Medicine
• Shared Decision Making and Communication
• Sleep Medicine
• Sports Medicine
• Stem Cell Transplantation
• Substance Use and Addiction Medicine
• Surgical Innovation
• Surgical Pearls
• Teachable Moment
• Technology and Finance
• The Art of JAMA
• The Arts and Medicine
• The Rational Clinical Examination
• Tobacco and e-Cigarettes
• Translational Medicine
• Trauma and Injury
• Treatment Adherence
• Ultrasonography
• Users' Guide to the Medical Literature
• Vaccination
• Venous Thromboembolism
• Veterans Health
• Women's Health
• Workflow and Process
• Wound Care, Infection, Healing
• Register for email alerts with links to free full-text articles
• Access PDFs of free articles
• Manage your interests
• Save searches and receive search alerts

ADHD symptoms persist into adulthood, with some surprising impacts on life success

A ttention Deficit Hyperactivity Disorder (ADHD) is often misconceived as a disorder that fades with age, a misconception debunked by recent findings published in the Journal of Attention Disorders . The study found that ADHD symptoms not only persisted over a 15-year period but also were related to various aspects of life success, including relationships and career satisfaction.

ADHD is a psychiatric disorder characterized primarily by inattention, such as difficulty maintaining focus, and hyperactivity-impulsivity, such as restlessness or impulsive actions. Historically regarded as a childhood condition, extensive research now shows that ADHD often persists into adulthood, affecting about 1% to 3% of the global population.

Symptoms of hyperactivity tend to decrease from childhood to adolescence, while inattention often remains stable. This stability can lead to significant challenges in social interactions, academic and job performance, and emotional regulation.

Given the persistent nature of ADHD and its impact on life outcomes, the researchers aimed to further investigate how symptoms of inattention and hyperactivity-impulsivity evolve from young adulthood into early middle age and their consequent effects on life success. They also sought to explore potential gender differences in these outcomes.

“My personal interest in this research on ADHD comes from my experience with friends and colleagues who have ADHD,” said study author Colin Henning , a PhD student at Trent University and member of the Emotion and Health Research Lab .

“Their ADHD diagnoses didn’t disappear as they got older (contrary to what they were told as kids) and instead their symptoms continued to impact their lives in a multitude of ways. I wasn’t able to find a lot of previous research on the extent to which ADHD continues through adulthood, so I wanted to help fill this gap in knowledge to get answers for the people in my own life that experience ADHD symptoms.”

The study began with an initial sample of 320 post-secondary students who were assessed for symptoms of ADHD at the start of their university studies. During their first week of university classes, these students were asked to complete a comprehensive questionnaire package. This package included the Conners Adult ADHD Rating Scale (CAARS), which is widely recognized for its efficacy in evaluating the presence and severity of ADHD symptoms.

Approximately 15 years after their initial assessment, a subset of these individuals was contacted for a follow-up study. This follow-up aimed to reassess the ADHD symptoms and evaluate life success across several domains including relationship quality and career satisfaction. Additional demographic and life situation data were collected to provide context to the ADHD assessments and life success measures.

One of the key findings was the strong stability of ADHD symptoms over the 15-year period. Both inattention and hyperactivity-impulsivity symptoms were found to be remarkably consistent over time.

More importantly, the researchers found that the presence of ADHD symptoms, particularly inattention, during emerging adulthood was consistently associated with poorer outcomes in key areas of life success during early middle adulthood. This was especially true for men.

In the realm of relationships, the data revealed that inattention symptoms adversely affected relationship quality, with participants reporting lower overall satisfaction. This suggests that difficulties in maintaining focus and managing tasks can extend into personal interactions, potentially leading to conflicts or misunderstandings in long-term relationships.

Regarding career outcomes, the participants with higher inattention symptoms reported lower career satisfaction. This could be linked to the challenges that inattention presents in workplace settings, such as difficulty in completing tasks efficiently, managing time, or maintaining productivity, which are critical factors for career progression and satisfaction.

“For the average person reading about our research, the main takeaway is that ADHD symptoms don’t just go away as you get older without treatment,” Henning told PsyPost. “Our findings show this notion that children and young adults with ADHD ‘just grow out of it’ when they get older is really a myth. Instead, symptom largely continue throughout young adulthood and into midlife, with these symptoms still affect people in their relationships and workplaces.”

The impact of hyperactivity-impulsivity symptoms on life success outcomes, however, was less straightforward than that of inattention.

Unlike inattention, which consistently predicted lower career satisfaction, hyperactivity-impulsivity symptoms did not consistently correlate with negative career outcomes. The impact seemed to vary more significantly between individuals. In some cases, traits associated with hyperactivity-impulsivity, such as energy and action orientation, might contribute positively to certain job roles or industries that value dynamic and quick decision-making skills.

Similarly, while inattention clearly had a negative correlation with relationship satisfaction, hyperactivity-impulsivity did not show a uniform negative impact. Among men, the researchers found that hyperactivity-impulsivity symptoms had a significant association with relationship satisfaction.

“We were surprised to find that reports of more hyperactive and impulsive behaviour among young adults (ages 18 to 25 years old) actually predicted people have more satisfying relationships and jobs later in life when we controlled for current behavior,” Henning said. “This was the opposite of what we expected to find and what other research has found.”

“In our paper, we propose this may be connected to how young people form identities, through exploration. In other words, young people with more hyperactive and impulsive behaviours may engage in exploring more jobs and relationships than the average person and this may allow them to find a more satisfying romantic partner and job over time instead of sticking to a less satisfying partner or job. That is of course if these same hyperactive and impulsive behaviors don’t continue to cause problems later in life.”

While the study provides valuable insights, it has limitations, such as the reliance on self-reported data and the lack of external validation for ADHD diagnoses. The study also cannot confirm that ADHD symptoms directly cause negative impacts on life success. Future research could address these limitations by incorporating more objective measures and broader diagnostic assessments.

“A major caveat of this research is that we didn’t specifically study people who have a diagnosis of ADHD,” Henning noted. “We studied average Canadians who attended university. So we need to conduct more research to see if these findings are the same for people with a diagnosis of ADHD.”

“Our long-term goals for this research is to expand our understanding of ADHD across the whole lifespan,” the researcher added. “We currently know a lot about ADHD in children and young adults. But we want to study people in midlife and later in life to better understand how ADHD affects people through their entire lives and possibly how to manage these effects.”

The study, “ Longitudinal Associations Between Symptoms of ADHD and Life Success: From Emerging Adulthood to Early Middle Adulthood ,” was authored by Colin T. Henning, Laura J. Summerfeldt, and James D. A. Parker.

New study challenges previous reports linking Tylenol use during pregnancy to autism, ADHD

The new study is challenging other research linking the use of acetaminophen during pregnancy to neurological disorders like autism and adhd..

Multiple studies linking the use of acetaminophen (Tylenol) during pregnancy to neurological disorders like autism and attention deficit hyperactivity disorder (ADHD) are being challenged by a new study that has just emerged from the Karolinska Institute in Sweden and Drexel University.

The study , published in the peer-reviewed medical journal JAMA on Tuesday, analyzed about 2.5 million children born between 1995 and 2019, and found "no evidence of increased risk of autism or ADHD associated with acetaminophen use," according to the study. However, it did find a "marginally increased risk" in models without "sibling controls."

Important to the study was its sibling analysis, conducted to look at full siblings who share both genetic and environmental components. There was no risk found in those observations, which suggests that variables observed in other models may be contributing to skewed data.

“Matched sibling control studies better control for environmental factors that are unknown to the investigators,” Dr. Eric Brenner, an assistant professor of pediatrics at Duke University, said in an email to CNN . Brenner was not involved in the study.

“Sibling controls will most likely grow up in the same home, have similar diets, and will be exposed to similar environments which allows investigators to better control for environmental factors.”

'Admissible evidence': federal judge rules against 440 Tylenol lawsuits

A federal judge ruled that 440 lawsuits against Tylenol makers do not have "admissible evidence" showing a link between prenatal use of Tylenol and autism or ADHD, according to reporting by ABC News.

U.S. District Judge Denise Cote wrote in her  opinion  that the presentations of some experts seemed to be "cherry-picked and misrepresented study results." The judge acknowledged that at least one expert "refused to acknowledge the role of genetics in the etiology of either ASD or ADHD."

The strength of the recent study published in JAMA is its duration and number of participants. The results that show no real risk of acetaminophen use during pregnancy as a contributing factor to autism and ADHD are in agreement with the American College of Obstetricians and Gynecologists, which maintains the painkiller is safe for pregnant women to use.

A committee of the Society for Maternal-Fetal Medicine, a 5,000-member nonprofit,  determined in 2017  that "the weight of evidence is inconclusive," USA TODAY previously reported.

The U.S. Food and Drug Administration  has chosen to not weigh in on the ongoing lawsuits. The FDA publicly commented on the issue in 2015 when it stated it was investigating concerns . After reviewing studies, the FDA noted "potential limitations" and maintained its stance that Tylenol for pain in pregnancy is safe at this time.

Contributing: Karen Weintraub

No Increased Risk Of Autism Or ADHD From Acetaminophen Use During Pregnancy, Study Suggests

• Share to Facebook
• Share to Twitter
• Share to Linkedin

A new study which compared siblings who were and weren’t exposed to acetaminophen during pregnancy found the drug doesn’t increase the risk of autism and ADHD, adding new evidence to a long-debated topic.

A pregnant mother holding her belly.

The researchers followed millions of children for 26 years after they were born, and they did see a small increase in ADHD, autism and intellectual disability in the overall population compared to when they were younger; around 7.5% were exposed to acetaminophen (the active ingredient in Tylenol) during pregnancy.

The risk of developing these neurodevelopmental disorders in kids who weren’t exposed to acetaminophen before birth versus those who were was 1.33% vs 1.53% for autism, 2.46% vs 2.87% for ADHD, and 0.70% vs 0.82% for intellectual disability, according to the study published Tuesday in JAMA Network Open.

However, the researchers decided to also use a sibling model to examine the risks, because prenatal acetaminophen exposure was more common in kids with parents who smoked during pregnancy, had lower socioeconomic status and previous diagnoses of neurodevelopmental disorders , all potential risk factors for ADHD and autism.

They didn’t find any increased risk when comparing siblings who were exposed to acetaminophen before birth and those who weren't exposed, meaning the increased risk of developing neurodevelopmental disorders may be due to other factors like genetics.

Some previous research has concluded prenatal acetaminophen use may increase the risk of neurobehavioral issues, but the current study found no evidence to support a cause-and-effect link when using a sibling model.

The study researchers noted that because siblings share a large portion of the same genetic background and may be exposed to similar environmental factors during pregnancy, comparing siblings—which most previous studies didn’t do—helps to control for these outside factors.

Acetaminophen is the only pain reliever generally considered safe for use during pregnancy, but many pregnant people may not take acetaminophen due to fears of potentially harmful side effects, so the researchers are hopeful this study provides “​​reassurance” to expectant parents.

Crucial Quote

“This study’s findings may be welcome news for birthing people who use acetaminophen as a pain or fever management option, since there are few safe alternatives for relief available,” Renee Gardner, a study author and principal researcher at Sweden’s Karolinska Institutet, said in a statement.

2.4 million. That’s how many children—who were all born in Sweden—were used as a part of this cohort, making this the largest study to date to examine the connection between Tylenol and ADHD, autism and intellectual disability, according to the study.

Acetaminophen’s link to neurodevelopmental disorders has been a controversial topic within the health community, as several studies have previously found the drug does cause an increase in neurobehavioral issues. Children whose umbilical cord blood samples had the highest doses of acetaminophen were around three times more likely to develop ADHD and autism, according to a separate JAMA study published in 2019. An international group of researchers recommended in 2021 that pregnant individuals limit their exposure by using the lowest effective dose for the shortest amount of time, and called for more warnings around taking acetaminophen during pregnancy, according to research published in Nature Reviews Endocrinology. However, they noted other factors like maternal alcohol use and stress may also play a role. Long term acetaminophen use during pregnancy resulted in a 20% higher risk of autism and a 30% higher risk of ADHD, a 2018 meta analysis published in the American Journal of Endocrinology found.

Key Background

A separate 2021 study also used a sibling model to examine this link, and it found both the exposed and unexposed children of mothers who took acetaminophen during pregnancy had an increased risk of developing ADHD. The researchers concluded these results may be partly due to “unobserved familial factors.” The Food and Drug Administration said in 2015 evidence was too “limited” to make any recommendations against using over-the-counter medications like acetaminophen during pregnancy. A class action lawsuit was brought against the makers of Tylenol and similar generic versions of the drug partially due to the recommendations from the 2021 Nature paper. However, a federal judge ruled in December 2023 the research cited in the lawsuit cannot be used as evidence since at least one of experts the plaintiffs used "cherry-picked and misrepresented study results and refused to acknowledge the role of genetics in the etiology of either [autism spectrum disorder] or ADHD." In September 2023, the FDA declined to comment on the lawsuit, though it conducted a new review of more recent studies earlier that year and said they were “limited” and “inconsistent.” Other medical bodies like the American College of Obstetricians and Gynecologists (ACOG) maintain that acetaminophen use during pregnancy is safe in moderation.

Further Reading

Federal judge says research can't be used to link acetaminophen to autism, ADHD (ABC News)

• Editorial Standards
• Reprints & Permissions