An international consensus statement by the World Federation of ADHD documented 208 evidence-based conclusions about Attention Deficit /Hyperactivity Disorder (ADHD) in a paper published last month (September 2021) on the Science Direct website.
The paper updates the International Consensus Statement, cataloging important scientific discoveries from the last 20 years and providing current, accurate information about ADHD that is supported by a substantial, rigorous body of evidence.
The authors identified evidence-based statements about ADHD through expert scrutiny of published high quality meta-analyses and very large studies. The term “evidence-based” is used in the document to refer to evidence that meets the inclusion/exclusion criteria the authors used in the literature search.
Expert scrutiny was provided by a project Steering Committee that included representatives from the following professional groups dedicated to research and clinical care of ADHD: The World Federation of ADHD, EUropean NETwork for Hyperkinetic DIsorderS (Eunethydis), the American Professional Society of ADHD and Related Disorders, the Canadian ADHD Resource Alliance, the Asian Federation of ADHD, the Latin American League of ADHD, the Australian ADHD Professionals Association, the Israeli Society of ADHD, the Saudi ADHD Society, Neurodevelopmental Disorders Across Lifespan section of the European Psychiatric Association, the ADHD Guidelines Group of the Association of Medical Scientific Societies in Germany, the ADHD Network of European College of Neuropsychopharmacology, the Chinese Society of Child and Adolescent Psychiatry and the ADHD Section of the World Psychiatric Association.
Here are the summarized findings documented in the report, along with the item numbers that support each statement.
|The syndrome we now call ADHD has been described in the medical literature since 1775.||1–13|
|When made by a licensed clinician, the diagnosis of ADHD is well-defined and valid at all ages, even in the presence of other psychiatric disorders, which is common.||14–19|
|ADHD is more common in males and occurs in 5.9 % of youth and 2.5 % of adults. It has been found in studies from Europe, Scandinavia, Australia, Asia, the Middle East, South America, and North America.||20–25|
|ADHD is rarely caused by a single genetic or environmental risk factor but most cases of ADHD are caused by the combined effects of many genetic and environmental risks each having a very small effect.||26–62|
|People with ADHD often show impaired performance on psychological tests of brain functioning, but these tests cannot be used to diagnose ADHD.||63–70|
|Neuroimaging studies find small differences in the structure and functioning of the brain between people with and without ADHD. These differences cannot be used to diagnose ADHD.||71–77|
|People with ADHD are at increased risk for obesity, asthma, allergies, diabetes mellitus, hypertension, sleep problems, psoriasis, epilepsy, sexually transmitted infections, abnormalities of the eye, immune disorders, and metabolic disorders.||78–100|
|People with ADHD are at increased risk for low quality of life, substance use disorders, accidental injuries, educational underachievement, unemployment, gambling, teenage pregnancy, difficulties socializing, delinquency, suicide, and premature death.||101–136|
|Studies of economic burden show that ADHD costs society hundreds of billions of dollars each year, worldwide.||137–147|
|Regulatory agencies around the world have determined that several medications are safe and effective for reducing the symptoms of ADHD as shown by randomized controlled clinical trials.||148–157|
|Treatment with ADHD medications reduces accidental injuries, traumatic brain injury, substance abuse, cigarette smoking, educational underachievement, bone fractures, sexually transmitted infections, depression, suicide, criminal activity and teenage pregnancy.||158–177|
|The adverse effects of medications for ADHD are typically mild and can be addressed by changing the dose or the medication.||178–188|
|The stimulant medications for ADHD are more effective than non-stimulant medications but are also more likely to be diverted, misused, and abused.||189–194|
|Non-medication treatments for ADHD are less effective than medication treatments for ADHD symptoms, but are frequently useful to help problems that remain after medication has been optimized.|
Apart from statements about the history of ADHD and its diagnostic criteria, the authors required each evidence-based statement to be supported by meta-analyses or by large registry studies with more than 2000 participants, and required meta-analyses to report data from five or more studies or 2000 or more participants.
“Moderate” is used as a synonym for “medium,” and “strong” for “large.” A “small” effect is generally difficult to observe in an individual but may be very important for public health if it concerns a common exposure that affects many children. A “medium” effect is expected to be noticeable to a careful observer (Cohen, 1988). A “large” effect is generally relevant to clinical practice at the level of the individual.
“If a topic is not included in this document, it does not mean the topic is unimportant; rather, it means the evidence found was insufficient to allow firm conclusions. This could be because there were insufficient studies of quality, because no attempt was made to assess publication bias, or because the data available did not support the claims made,” the authors wrote.
“Our search strategy generated 208 empirically supported statements about ADHD,” they wrote.
The status of the included statements as empirically supported was approved by the 80 authors from 27 countries and 6 continents, and was endorsed by 366 people who have read this document and agree with its contents.
One limitation of the consensus statement is that the authors do not report well-established research findings for which meta-analyses or very large studies do not exist. “The absence of such a study is not always an indication of knowledge of absence of an effect,” they pointed out.
How is ADHD diagnosed?
ADHD can only be diagnosed by a licensed clinician who interviews the parent or caregiver and/or patient to document criteria for the disorder (American Psychiatric Association, 2013; Chinese Society of Psychiatry, 2001; Faraone et al., 2015; Feldman and Reiff, 2014; Pearl et al., 2001; Stein, 2008; World Health Organization, 2018), the authors noted. It cannot be diagnosed by rating scales alone, neuropsychological tests, or methods for imaging the brain.
The main features of the diagnosis are:14
The diagnosis requires: 1) the presence of developmentally inappropriate levels of hyperactive-impulsive and/or inattentive symptoms for at least 6 months; 2) symptoms occurring in different settings (e.g., home and school); 3) symptoms that cause impairments in living; 4) some of the symptoms and impairments first occurred in early to mid-childhood; and 4) no other disorder better explains the symptoms (American Psychiatric Association, 2013; World Health Organization, 2018; Yi and Jing, 2015).15
The clinical presentation of ADHD can be described as primarily inattentive, primarily hyperactive-impulsive, or combined, depending on the nature of their symptoms (American Psychiatric Association, 2013). Meta-analyses indicate that inattention is more strongly associated with academic impairment, low self-esteem, negative occupational outcomes, and lower overall adaptive functioning. Hyperactive-impulsive symptoms are associated with peer rejection, aggression, risky driving behaviors, and accidental injuries. Patterns of associated disorders also differ between the dimensions (Willcutt et al., 2012).16
ADHD impairs the functioning of highly intelligent people, so the disorder can be diagnosed in this group. A population-based birth cohort study of over 5700 children found no significant differences among children with high, average, or low IQ and ADHD in median age at which ADHD criteria were met, rates of learning disorders, psychiatric disorders, and substance abuse, and rates of stimulant treatment (Katusic et al., 2011; Rommelse et al., 2017).17
In adolescence and young adulthood, many individuals with a history of childhood ADHD continue to be impaired by the disorder, although they often show reduced hyperactivity and impulsivity while retaining symptoms of inattention (Faraone et al., 2006).18
Many large epidemiologic and clinical studies show that ADHD often co-occurs with other psychiatric disorders, especially depression, bipolar disorder, autism spectrum disorders, anxiety disorders, oppositional defiant disorder, conduct disorder, eating disorders, and substance use disorders (Bernardi et al., 2012; Chen et al., 2018c; Groenman et al., 2017; Nazar et al., 2016; Solberg et al., 2018; Tung et al., 2016; Yao et al., 2019). Their presence does not rule out a diagnosis of ADHD.19
A meta-analysis comprising 25 studies with over eight million participants found that children and adolescents who are relatively younger than their classmates are more likely to have been diagnosed with ADHD (Caye et al., 2020)
ADHD is a common disorder
A meta-analysis of 19 studies with over 55,000 participants found that 5.9 % of youths meet diagnostic criteria for ADHD (Willcutt, 2012). Another meta-analysis, with 135 studies and about a quarter of a million youths, found no significant differences in prevalence between North America and Europe, Asia, Africa, South America, and Oceania (Polanczyk et al., 2014).
A meta-analysis of six studies with over 5300 participants estimated the prevalence of ADHD in adulthood to be 2.5 % (Simon et al., 2009). A meta-analysis of 20 studies encompassing 13 countries and seven regions/metropolitan areas, involving more than 26,000 participants, estimated that 2.8 % of adults meet criteria for ADHD (Fayyad et al., 2017). The lower prevalence in adults compared with youths is consistent with a meta-analysis of 21 studies with over 1600 participants showing that only about one in six youths with ADHD still meet full diagnostic criteria for ADHD at age 25, and about half show signs of residual impairment (Faraone et al., 2006).
A meta-analysis of nine studies with a total of over 32,000 older adults found a prevalence of 2.2 % based on ADHD rating scales, dropping to 1.5 % when limited to persons at least fifty years old. Yet a meta-analysis of seven studies with over 11.7 million participants based on ADHD clinical diagnoses, performed by the same team, reported a prevalence of only 0.2 % for persons at least fifty years old. A third meta-analysis performed by the same researchers, of four studies with over 9.2 million participants, found an ADHD treatment rate of only 0.02 % among persons at least fifty years old (Dobrosavljevic et al., 2020).
A meta-analysis of 19 studies encompassing over 150,000 U.S. Black youths under 18 years old reported an ADHD prevalence rate of 14 %. The authors concluded, “Black individuals are at higher risk for ADHD diagnoses than the general US population. These results highlight a need to increase ADHD assessment and monitoring among Black individuals from different social backgrounds” (Cénat et al., 2021).
ADHD is more common in males. A meta-analysis of parent ratings of symptoms in 29 studies with over 42,000 participants, and teacher ratings in 24 studies with over 56,000 participants, found a roughly two-to-one male/female ratio in youth (Willcutt, 2012).
Genetic, Environmental Factors Cause ADHD
A review of 37 twin studies from the United States, Europe, Scandinavia, and Australia found that genes and their interaction with the environment must play a substantial role in causing ADHD (Faraone and Larsson, 2018; Larsson et al., 2014a; Pettersson et al., 2019).
In a genomewide study, an international team analyzed DNA from over 20,000 people with ADHD and over 35,000 without ADHD from the United States, Europe, Scandinavia, China, and Australia. They identified many genetic risk variants, each having a small effect on the risk for the disorder (Demontis et al., 2019). This study confirmed a polygenic cause for most cases of ADHD, meaning that many genetic variants, each having a very small effect, combine to increase risk for the disorder. The polygenic risk for ADHD is associated with general psychopathology (Brikell et al., 2020) and several psychiatric disorders (Lee et al., 2019a,b).
Additional genes have been implicated by meta-analyses, but their status as risk genes remains uncertain until validated in a genomewide study. These genes are ANKK1 (Pan et al., 2015) DAT1 (Grunblatt et al., 2019b), LRP5 and LRP6 (Grunblatt et al., 2019a), SNAP25 (Liu et al., 2017b), ADGRL3 (Bruxel et al., 2020) DRD4 and BAIAP2 (Bonvicini et al., 2020, 2016).
The polygenic risk for ADHD predicts ADHD symptoms in the population, suggesting that the genetic causes of ADHD as a disorder also influence sub-threshold levels of ADHD symptoms in the population (Demontis et al., 2019; Taylor et al., 2019).
In the population, those with a high polygenic risk for ADHD are more likely to have been diagnosed with ADHD (Li, 2019), anxiety, or depression (Martin et al., 2018).
ADHD can also be the result of rare single gene defects (Faraone and Larsson, 2018) or abnormalities of the chromosomes (Cederlof et al., 2014). When the DNA of 8000+ children with autism spectrum disorder (ASD) and/or ADHD and 5000 controls was analyzed, those with ASD and those with ADHD had an increased rate of rare genetic mutations compared with controls (Satterstrom et al., 2019).
Family, twin, and DNA studies show that genetic and environmental influences are partially shared between ADHD and many other psychiatric disorders (e.g. schizophrenia, depression, bipolar disorder, autism spectrum disorder, conduct disorder, eating disorders, and substance use disorders) and with somatic disorders (e.g. migraine and obesity) (Demontis et al., 2019) (Faraone and Larsson, 2018) (Ghirardi et al., 2018) (Lee et al., 2019a,b) (Lee et al., 2013) (Anttila et al., 2018; Tylee et al., 2018) (van Hulzen et al., 2017) (Vink and Schellekens, 2018) (Brikell et al., 2018) (Chen et al., 2019a) (Yao et al., 2019).
However, there is also a unique genetic risk for ADHD. Evidence of shared genetic and environmental risks among disorders suggest that these disorders also share a pathophysiology in the biological pathways that dysregulate neurodevelopment and create brain variations leading to disorder onset.
Very large studies of families suggest that ADHD shares genetic or familial causes with autoimmune diseases (Li et al., 2019), hypospadias (Butwicka et al., 2015), and intellectual disability (Faraone and Larsson, 2018).
Environment plays a part
A pair of meta-analyses found small correlations between lead burden and inattention symptoms (27 studies, over 9300 youths) and hyperactivity-impulsivity symptoms (23 studies, over 7800 youths) (Goodlad et al., 2013).
A more recent meta-analysis of 14 studies with over 17,000 children reported that higher blood lead levels were associated with quadrupled odds of ADHD (Nilsen and Tulve, 2020).
A study of over 2500 youths from the National Health and Nutrition Examination Survey, a cross-sectional, nationally representative sample of the U.S. population, found that those with blood lead levels in the top third were 2.3 times more likely to have ADHD compared with those in the bottom third (Froehlich et al., 2009). A similar study, with over 4700 youths from the same national survey, found that those with blood lead levels in the highest fifth were four times more likely to have ADHD compared with those in the bottom fifth (Braun et al., 2006).
Three meta-analyses with over twenty studies covering more than three million persons have found prenatal exposure to maternal smoking associated with a greater than 50 % increase in incidence of ADHD (Huang et al., 2018a) (Dong et al., 2018; Nilsen and Tulve, 2020).
However: Although this association has also been seen in large population studies (Joelsson et al., 2016; Obel et al., 2016; Skoglund et al., 2014), it disappears after adjusting for family history of ADHD, which indicates that the association between maternal smoking during pregnancy and ADHD is due to familial or genetic factors that increase the risk for both smoking and ADHD.
Nevertheless, a meta-analysis of nine studies spanning three continents and over 100,000 participants found that childhood exposure to secondhand cigarette smoke was associated with a 60 % greater likelihood of ADHD. It was unclear to what extent the association was causal versus due to confounders (Huang et al., 2021).
In a meta-analysis of 15 double-blind, placebo-controlled trials with 219 participants, artificial food dyes were associated with a small increase in hyperactivity in children (Schab and Trinh, 2004). Another meta-analysis, covering 20 studies with a combined total of 794 individuals, found a very small increase in ADHD symptoms, but only when rated by parents, not by teachers or other observers (Nigg et al., 2012).
In a Taiwanese study of over 10,000 births, maternal use of acetaminophen during pregnancy was associated with a 33 % greater likelihood of ADHD in their children (Chen et al., 2019b).
Another study, examining 113,000 offspring from the Norwegian Mother and Child Cohort Study and the Norwegian Patient Registry, including 2246 with ADHD, found a dose-response relationship between maternal prenatal use of acetaminophen and ADHD (Ystrom et al., 2017).
A nationwide study using the Danish national registers looked at 913,000 children born between 1997 and 2011. Prenatal exposure to the anti-epileptic drug valproate was associated with a 50 % greater risk of ADHD. No associations were found for other anti-epileptic drugs (Christensen et al., 2019).
Organophosphate pesticides are potent neurotoxins. In a sample of 1139 children from the U.S. population, a tenfold increase in the organophosphate metabolite dimethyl alkylphosphate (DMAP) was associated with 55 % increase in the probability of having ADHD. Children with detectable levels of the most-commonly detected DMAP metabolite were twice as likely to have ADHD compared with those with undetectable levels (Bouchard et al., 2010).
A meta-analysis found no significant effect of two classes of air pollutants – particulate matter (six studies, over 51,000 persons) and nitrogen oxides (five studies, over 51,000 persons) (Zhang et al., 2020b).
A Taiwan-wide longitudinal cohort study geolinking over 16,000 mother-infant pairs to levels of air pollutants found no association between small particulate matter levels, sulphur dioxide levels, or nitrogen dioxide levels during gestation and ADHD diagnoses in the first eight years of their offsprings’ lives. It did find 25 % greater odds for having ADHD with exposures to nitric oxide, a common traffic pollutant (Shih et al., 2020).
A meta-analysis of nine European population studies encompassing 4826 mother-child pairs examined the relationship between exposure to Perfluoroalkyl Substances (PFAS) via breast milk in infancy and development of ADHD. No associations were found in exposure to PFAS with ADHD in offspring (Forns et al., 2020).
A meta-analysis of seven studies encompassing a total of over 25,000 participants from six countries on three continents found no evidence of an association between sugar consumption and ADHD in youth (Farsad-Naeimi et al., 2020)
Nutrition also has a role
A meta-analysis of nine studies and 586 people found moderately lower overall blood levels of omega-3 PUFAs in ADHD than non-ADHD youth (Hawkey and Nigg, 2014).
A nationwide population-based case-control study using the Finnish national registers compared 1067 patients with ADHD born between 1998 and 1999 with 1067 matched controls. Lower maternal vitamin D levels were associated with a roughly 50 % greater likelihood of ADHD in their children (Sucksdorff et al., 2021).
Pregnancy and birth are factors
A meta-analysis of twelve studies with over 6000 participants found a threefold increase in the rate of ADHD among very/extremely preterm or very/extremely low birth weight babies (Franz et al., 2018).
Another meta-analysis, combining 85 studies with a total of over 4.6 million births, found a small-to-moderate correlation between low birth weight and ADHD (Momany et al., 2018).
A Swedish national register study of 1.2 million children found a stepwise increase in the likelihood of ADHD with increasing prematurity. Results were not due to having an ADHD relative or socioeconomic stress (Lindstrom et al., 2011). Similar results were reported from the Finnish national registers when comparing over 10,000 people with ADHD with over 38,000 controls (Sucksdorff et al., 2015).
A meta-analysis of six studies combining 1.4 million people found that children whose mothers had hypertensive disorders during pregnancy had a 25 % increase in the rate of ADHD (Maher et al., 2018).
Two meta-analyses, one with seven studies with over 28,000 participants and another with three studies and over 1.4 million participants, found that children of obese mothers were roughly 60 % more likely to develop ADHD (Jenabi et al., 2019; Sanchez et al., 2018).
A study of over 80,000 mother-child pairs participating in the Danish National Birth Cohort reported an almost 50 % elevated risk of ADHD in children of obese mothers and a doubled risk in children of severely obese mothers (Andersen et al., 2018).
A meta-analysis of two large cohort studies with a combined total of over 3.1 million persons found a slight but significant association between maternal hyperthyroidism during pregnancy and ADHD in offspring. A second meta-analysis of four cohort studies encompassing over 3.4 million participants likewise found a slight but significant association between maternal hypothyroidism and ADHD in offspring. No attempt was made to assess the role of confounders (Ge et al., 2020).
A nationwide population-based cohort study using Danish registers compared over 29,000 children born to women who lost a close relative during pregnancy with a million other children in the same cohort and found that boys born to these women were twice as likely to have ADHD (Li et al., 2010).
A U.S. population-based study of over 14,000 participants in the National Longitudinal Study of Adolescent Health found that after adjusting for demographic, socioeconomic, and familial risk factors for child maltreatment, ADHD inattentive type was associated with having been exposed to sexual abuse and physical neglect (Ouyang et al., 2008).
A Danish national register longitudinal cohort study of a million people found that Rutter’s indicators of adversity were predictive of ADHD. Out-of-home care was strongly predictive; low social class, paternal criminality, maternal mental disorder, and severe marital discord were moderately predictive. Large family size had no effect (Ostergaard et al., 2016).
In a sample of 4122 U.S. youths with ADHD from the 2016 U.S. National Survey of Children’s Health, greater family cohesion and community support decreased the risk for moderate to severe ADHD (Duh-Leong et al., 2020).
Brain studies reveal more information
A recent meta-meta-analysis included 34 meta-analyses of neurocognitive profiles in ADHD (all ages) concerning 12 neurocognitive domains. Those with ADHD had moderate impairments in multiple domains (working memory, reaction time variability, response inhibition, intelligence/achievement, planning/organization). Effects were larger in children and adolescents than in adults (Pievsky and McGrath, 2018).
A meta-analysis of 49 studies and over 8200 children and adolescents found moderate impairments in working memory in those with ADHD. These deficits declined with age (Ramos et al., 2020).
A meta-analysis of randomized controlled trials (RCTs) with preschoolers found that cognitive training led to moderate improvement in working memory (23 studies, over 2000 participants) and small-to-moderate improvement in inhibitory control (26 studies, over 2200 participants) (Pauli-Pott et al., 2020).
An analysis of structural magnetic resonance imaging (MRI) data from 36 cohorts with a total of over 4100 participants found slightly reduced total cortical surface area in children with ADHD. The same team found some subcortical regions of the brain were smaller in children with ADHD, mainly in frontal, cingulate, and temporal regions with some reductions in cortical thickness in temporal regions. The same team found some subcortical regions of the brain, i.e., basal ganglia, amygdala, hippocampus, and intracranial volumes were smaller in children with ADHD in 23 cohorts of 3242 participants. The differences seen in children were not seen in adolescents or adults (Hoogman et al., 2017, 2019). All of the differences observed were small to very small and subtle.
A meta-analysis of 21 functional MRI studies with 607 participants found that those with ADHD showed consistent and replicable under-activation in typical regions of inhibitory control such as right inferior frontal cortex, supplementary motor area and the basal ganglia relative to typically developing individuals (Hart et al., 2013).
The inferior frontal under-activation findings were replicated in two further fMRI meta-analyses of inhibitory control with 33 datasets/1161 participants, and 42 datasets/2005 participants, respectively (Lukito et al., 2020; Norman et al., 2016).
Another meta-analysis including 130 fMRI studies with 1914 participants found no convergence except for aberrant function in basal ganglia for neutral fMRI tasks and inferior frontal under-function in males only (Samea et al., 2019).
Meta-analyses and systematic reviews showed that the medications used to treat ADHD are not associated with observed deficits in brain structure (Hoogman et al., 2017, 2019; Lukito et al., 2020; Norman et al., 2016; Spencer et al., 2013), but with improved brain function, most prominently in inferior frontal and striatal regions (Hart et al., 2013; Lukito et al., 2020; Norman et al., 2016; Rubia et al., 2014; Spencer et al., 2013).
ADHD linked to some non-psychiatric medical problems
A Swedish national register study of over 2.5 million people found ADHD patients had a threefold greater risk of obesity relative to their non-ADHD siblings and cousins. It also found a familial co-aggregation of ADHD and clinical obesity, the strength of which varied directly with the degree of genetic relatedness (Chen et al., 2018c).
A meta-analysis found that compared with typically developing people, children and adolescents with unmedicated ADHD were about 20 % more likely to be overweight or obese (15 studies, over 400,000 participants), and adults with unmedicated ADHD almost 50 % more likely to be overweight or obese (9 studies, over 45,000 participants) (Nigg et al., 2016). Meta-analyses of twelve studies with over 180,000 participants found that people with unmedicated ADHD were about 40 % more likely to be obese, whereas those who were medicated were indistinguishable from typically developing people (Cortese et al., 2016b).
In a meta-analysis of six longitudinal studies with over 50,000 participants, those with asthma or atopic eczema were a third more likely to have ADHD than controls. A meta-analysis of three studies with over 48,000 participants found that those with allergic rhinitis were about 50 % more likely to have ADHD (van der Schans et al., 2017).
A retrospective analysis of over 650,000 children and adolescents in German diagnosis and prescription databases found ADHD was 40 % more likely to be diagnosed among children with type 1 diabetes (T1DM) (Kapellen et al., 2016).
A longitudinal study using the Taiwan National Health Insurance Research Database enrolled over 35,000 patients with ADHD and over 70,000 age- and sex-matched controls. Adolescents and young adults with ADHD were about three times more likely to develop type 2 diabetes mellitus (Chen et al., 2018b).
A cohort study using multiple Swedish national registers looked at over 1.6 million adults aged 50–64 years. Prevalence of type 2 diabetes mellitus was 70 % greater among adults with ADHD (Chen et al., 2018c).
A meta-analysis of 18 studies with more than 2500 children and adolescents found a moderate association between sleep-disordered breathing and ADHD (Sedky et al., 2014).
In a Norwegian national registry study of over 1.2 million males and over 1.2 million females, males with ADHD were 30 % more likely to be diagnosed with psoriasis, and women with ADHD more than 50 % more likely to be diagnosed with psoriasis, than normally developing controls (Hegvik et al., 2018).
A Taiwan nationwide population cohort study of over 8000 people with ADHD and 32,000 matched controls explored associations with autoimmune diseases. It reported that those with ADHD had well over twice the prevalence of ankylosing spondylitis, ulcerative colitis, and autoimmune thyroid disease, and over 50 % greater likelihood of asthma, allergic rhinitis, and atopic dermatitis (Chen et al., 2017a).
A population-based cohort study of over 900,000 Danish children found that epilepsy was associated with a 2.7-fold increased risk for ADHD (Bertelsen et al., 2016). Another population-based cohort study, of over 12,000 Taiwanese, reported that epilepsy was associated with a 2.5-fold increased risk for ADHD. Conversely, a linked cohort study of over 18,000 Taiwanese found ADHD was associated with a fourfold increase in epilepsy (Chou et al., 2013).
Using Taiwan’s nationwide population-based dataset, over 116,000 children with ADHD were compared with the same number of randomly selected children without ADHD. Those with ADHD were much more likely to have significant abnormalities of the eye: almost 90 % more likely to have amblyopia (“lazy eye”), over 80 % more likely to have astigmatism, and twice as likely to have heterotropia, in which the eyes diverge at rest (Ho et al., 2020). A study using the same database matched 6817 youths diagnosed with amblyopia to over 27,000 age- and sex-matched controls. Those in the amblyopia group had 1.8 times the risk of developing ADHD (Su et al., 2019).
In a study of over 2.5 million German youth, those with ADHD were nine times more likely to have metabolic disorders, five times more likely to develop viral pneumonia, four times more likely to have white blood cell disorders, three times more likely to have kidney failure, high blood pressure, or be obese, two and a half times more likely to have type 2 diabetes or migraines, twice as likely to have asthma or atopic dermatitis, and 50 % more likely to have glaucoma (Akmatov et al., 2019). A Brazilian population-based study including 5671 children found those with migraine about four times more likely to have ADHD (Arruda et al., 2020).
A study of over 59,000 boys diagnosed with ADHD and over 52,000 healthy boys in Taiwan reported that those in the ADHD group were twice as likely to develop testicular dysfunction (Wang et al., 2019).
“ADHD is a disorder associated with serious distress and/or impairments in living,” the authors wrote. “Although, as documented . . . many severe adverse outcomes have been associated with ADHD, the typical patient does not experience all, or even most, of these problems. Many patients live enjoyable and productive lives, especially if they receive treatment.”
A cohort study of more than 2.2 million Taiwanese found no increased risk of death from natural-causes associated with ADHD. But people with ADHD had twice the rate of suicide, twice the rate of death by homicide, and a 30 % greater rate of death from unintentional injury (Chen et al., 2019c).
Using nationwide registers in Denmark, a cohort study of 2.9 million people reported a fourfold higher rate of suicide attempts and deaths in patients with ADHD. The risk was over tenfold in those with ADHD plus another psychiatric diagnosis (Fitzgerald et al., 2019).
A meta-analysis found that persons with ADHD attempted suicide at twice the rate of typically developing people (six studies, over 65,000 persons), had over three times the rate of suicidal ideation (23 studies, over 70,000 persons), and over six times the rate of completed suicide (four studies, over 130,000 persons) (Septier et al., 2019).
A Taiwanese study of over 20,000 adolescents and young adults with ADHD and over 61,000 age- and sex-matched non-ADHD individuals found that those with ADHD were almost four times as likely to attempt suicide, and over six times as likely to repeat suicide attempts.
Methylphenidate or atomoxetine treatment did not increase the risk of suicide attempts or repeated suicide attempts. Long-term methylphenidate treatment was associated with a lower risk for repeated suicide attempts among men (Huang et al., 2018b).
A study of the Danish population using nationwide registers found that, compared with other youth, those diagnosed with ADHD were more than twice as likely to be convicted of criminal offenses and were three times as likely to be incarcerated. After adjusting for other risk factors, those with ADHD were 60 % more likely to have been convicted of a crime, and 70 % more likely to have been incarcerated (Mohr-Jensen et al., 2019).
A study using a nationally representative American sample of over 5000 adults found that those with ADHD were over twice as likely to be perpetrators of physical dating violence, and 65 % more likely to be victims of such violence (McCauley et al., 2015).
A study using the Danish national registries looked at violent crimes against youths aged 7–18 years, among a total of 678,000 individuals. Children with ADHD were 2.7 times more likely to be victims of violent crimes than their typically developing peers, after adjusting for confounding risk factors (Christoffersen, 2019).
A study of a U.S. sample of almost 30,000 adults found that those with ADHD were twice as likely not to have graduated from high school on time, after adjusting for other psychiatric disorders (Breslau et al., 2011).
A meta-analysis of ten studies and 830 youths found that ADHD was strongly associated with poorer performance on measures of overall, expressive, receptive, and pragmatic language (Korrel et al., 2017).
A meta-analysis of twelve studies covering over 5400 people found that those with ADHD were almost three times more likely to be nicotine-dependent. Combining eleven studies with almost 2400 participants, those with ADHD were 50 % more likely to develop a drug or alcohol use disorder than those without ADHD (Lee et al., 2011).
A meta-analysis found that ADHD was associated with a more than twofold greater odds of alcohol-use disorders (13 studies, over 20,000 participants) and nicotine-related disorder (14 studies, over 1800 participants) (Groenman et al., 2017).
A Swedish study of over half a million people found a more than threefold association between ADHD and subsequent drug use disorders after adjusting for sex and parental education (Sundquist et al., 2015).
Studies of 2.7 million girls from Denmark (Ostergaard et al., 2017), 380,000 from Sweden (Skoglund et al., 2019) and 7500 from Taiwan (Hua et al., 2020) found that those with ADHD were more likely to have teen pregnancies than those without ADHD. Consistent with these results, large studies from Sweden (Chang et al., 2014a), Finland (Chudal et al., 2015) and a consortium of eight European countries (Pohlabeln et al., 2017) each found ADHD to be more likely among children of teenage mothers than among children of older mothers.
A study of over 36,000 people from the U.S. reported that ADHD increased the risks for problem gambling, spending too much money, reckless driving, and quitting a job without a plan for what to do next (Bernardi et al., 2012).
A nationwide study using Taiwan’s National Health Insurance Research Database compared 675 adults with ADHD and 2025 without ADHD, matched by age and sex. After adjusting for other psychiatric disorders, urbanization level of residence, and monthly income, those with ADHD had 3.4 times the risk of developing dementia (Tzeng et al., 2019).
A meta-analysis of nine studies encompassing almost a million and a half people found that ADHD is associated with a threefold greater risk of poisoning in children (Ruiz-Goikoetxea et al., 2018b). In a study from Taiwan comparing 3685 children with ADHD with 36,000 controls, those with ADHD had a more than fourfold greater risk of deliberate self-poisoning (Chou et al., 2014).
Using Danish registers, a nationwide population study of over 675,000 youths between the ages of 7 and 18 found that youths with ADHD were 3.7 times as likely to be reported as victims of sexual crimes than normally developing controls. After adjusting for covariates, such as parental violence, parental inpatient mental illness, parental suicidal behavior or alcohol abuse, parental long-term unemployment, family separation, and child in public care outside the family, youths with ADHD remained almost twice as likely to be reported as victims of sexual crimes (Christoffersen, 2020).
There are many more specific evidence-based conclusions that were drawn from the research. To access that information, click here.
Photo credit: Lavi Perchik via Unsplash
Reference: The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder, Neuroscience & Biobehavioral Reviews, Volume 128, September 2021, Pages 789-818, https://doi.org/10.1016/j.neubiorev.2021.01.022