Behavioral disinhibition is a trait associated with both ADHD and several genes that affect dopamine signaling. A new study by three American medical researchers set out to examine how these ADHD risk genes – DRD4 (dopamine 4 receptor density), DAT1 (dopamine 1 transporter), and DBH (dopamine beta-hydroxylase) – affect estimated life expectancy in young adulthood.

The method used was a longitudinal study of 131 hyperactive children and 71 matched controls through early adulthood. The original evaluations were done in 1979-1980, when both groups were children in the 4 to 12 age range. They were reevaluated in 1987-1988 as adolescents aged 12 to 20. The next follow-up was in 1992-1996 in early adulthood, aged 19 to 25. The final follow-up was in 1998-2004, as adults aged 24 to 32. All agreed to physical examinations that formed the basis for calculating estimated life expectancy using actuarial tables that factor in the effects of smoking, body mass index, alcohol, and other risk factors on expected longevity. Participants also provided blood samples that enabled gene typing.

For the DAT1 gene, participants who had the homozygous nine-repeat allele (9/9) had a five-year reduction in estimated life expectancy relative to those with the ten-repeat allele (10/10). Those with the intermediate (9/10) configuration had a three-year reduction in estimated life expectancy.

For the DBH Taq1 gene, those with a heterozygous (A1/A2) combination had almost a three-year reduction in estimated life expectancy relative to those with homozygous (A1/A1 or A2/A2) configurations.

For DRD4, on the other hand, no significant differences were found for estimated life expectancy.

In a related study, several background traits were found to be significantly predictive of variance in estimated life expectancy. The largest of these was behavioral disinhibition, followed by verbal IQ, self-rated hostility, and a nonverbal fluency test. But no significant differences were found between any of the gene polymorphisms on any of these four measures, indicating that the present gene associations were independent of the background traits.

The researchers next sought to determine which variables used in the estimated life expectancy calculations were associated with the two significant genes. For DBH, one variable stood out. Those with the A1/A2 heterozygous pairings had almost twice the alcohol consumption of those with homozygous pairings (p = 0.023).

For DAT1, two variables stood out. Overall, the 9/9 pairings smoked two and a half times as much as the 10/10 pairings, with the 9/10 pairings midway between the extremes (p = 0.036). They were also 73 percent more likely to be smokers relative to the 10/10 pairings, and 61 percent more likely relative to the 9/10 pairings. They also had significantly less education than the 10/10 pairings, with the 9/10 pairings again being intermediate (p = 0.027).

An obvious limitation of the study was its small sample size. The authors cautioned, “our findings should be considered quite preliminary and in need of much greater research before being given much weight in the literature or in public policy.”

“With these limitations in mind,” they concluded, “the present study demonstrated that two ADHD risk genes (DBH and DAT1) independently contributed to a reduction in ELE [estimated life expectancy] beyond the second order variables of behavioral disinhibition, IQ, hostility, and nonverbal fluency that contributed in the related study to variation in ELE. The gene polymorphisms seemed to be influencing ELE through their affiliation with first-order or more proximal factors related to ELE such as education, smoking, alcohol use, and possibly exercise.”

Russell A. Barkley, Karen Müller Smith, and Mariellen Fischer, “ADHD risk genes involved in dopamine signaling and metabolism are associated with reduced estimated life expectancy at young adult follow-up in hyperactive and control children,” American Journal of Medical Genetics (2019), DOI: 10.1002/ajmg.b.32711.

ADHD is far more prevalent among persons with AUD (roughly 20 percent) than it is in the general population. The most accurate way of identifying ADHD is through structured clinical interviews. Given that this is not feasible in routine clinical settings, ADHD self-report scales offer a less reliable but much less resource-intensive alternative. Could the latter be calibrated in a way that would yield diagnoses that better correspond with the former?

A German team compared the outcomes of both methods on 404 adults undergoing residential treatment for AUD. All were abstinent while undergoing evaluations. First, to obtain reliable ADHD diagnoses, each underwent the Diagnostic Interview for ADHD in Adults, DIVA. If DIVA indicated probable ADHD, two expert clinicians conducted successive follow-up interviews. ADHD was only diagnosed when both experts concurred with the DIVA outcome.

Participants were then asked to use two adult ADHD self-report scales, the six-item Adult ADHD Self Report Scale v1.1 (ASRS) and the 30-item Conners’ Adult ADHD Rating Scale (CAARS-S-SR). The outcomes were then compared with the expert interview diagnoses.

Using established cut-off values for the ASRS, less than two-thirds of patients known to have ADHD were scored as having ADHD by the test. In other words, there was a very high rate of false negatives. Lowering the cut-off to a sum score ≥ 11 resulted in correct diagnosis of more than seven out of eight. But the rate of false positives soared to almost two in five. Similarly, the CAARS-S-SR had its greatest sensitivity (ability to accurately identify those with ADHD) at the lowest threshold of ≥ 60, but at a similarly high cost in false positives (more than a third).

The authors found it was impossible to come anywhere near the precision of the expert clinical interviews. Nevertheless, they judged the best compromise to be to use the lowest thresholds on both tests, and then require positive determinations from both. That led to successfully diagnosing more than three out of four individuals known to have ADHD, with a false positive rate of just over one in five.

Using this combination of the two self-reporting questionnaires with lower thresholds, they suggest, could substantially reduce the under-diagnosis of ADHD in alcohol dependent patients.

Mathias Luderer, Nurcihan Kaplan-Wickel, Agnes Richter, Iris Reinhard, Falk Kiefer, Tillmann Weber, “Screening for adult attention-deficit/hyperactivity disorder in alcohol dependent patients: Underreporting of ADHD symptoms in self-report scales,” Drug and Alcohol Dependence (2019), 195:52-58.

A Danish team recruited 29,489 participants from among voluntary blood donors between the ages of 17 and 67, ensuring a large sample size. Participants were asked to complete two simple questionnaires on digital tablets. One asked two questions: “Have you ever had migraine?” and “Have you ever had visual disturbances lasting 5-60 min followed by headache?” A yes to either was considered positive for migraine. The other used the ADHD Self-Report Scale, with 18 ADHD symptoms evaluated on a five-point scale.

Excluding those who did not answer all questions left 26,456 participants. The risk for migraines among those with ADHD was nearly twice the risk for others. The odds ratio (OR) was 1.8, with a 95 percent confidence interval from 1.53 to 2.12 (p < 0.001). The OR was higher among females (2.01) than males (1.64). For those with visual disturbances, the OR was higher (1.98) than for those without (1.52). The association disappeared in those over 60, with an OR essentially equal to one (0.98, 95% CI = 0.84 – 1.15, p = 0.8).

Although the authors concluded, “We demonstrate a significant comorbidity between migraine and ADHD in adults, and this is most prominent for participants with migraine with visual disturbances,” the significance to which they refer are of the p-values, and should not be misinterpreted as an indication of a strong association, as the odds ratios point variably to weak, and weak-to-moderate associations, depending on subpopulations. The work is, however, important as it points to another somatic comorbidity of ADHD. That list is growing and now includes obesity, eczema and asthma.

Thomas Folkmann Hansen, Louise K. Hoeffding, Lisette Kogelman, Thilde Marie Haspang, Henrik Ullum, Erik Sørensen, Christian Erikstrup, Ole Birger Pedersen, Kaspar René Nielsen, Henrik Hjalgrim, Helene M. Paarup, Thomas Werge, and Kristoffer Burgdorf, “Comorbidity of migraine with ADHD in adults,” BMC Neurology (2018), 18:147.

All Swedish residents have their health records tracked through unique personal identity numbers. That makes it possible to identify psychiatric and medical disorders with great accuracy across an entire population, in this case encompassing more than five and a half million adults aged 18 to 64. A subgroup of more than 1.6 million persons between the ages of 50 and 64 enabled a separate examination of disorders in older adults.

Slightly over one percent of the entire population (about 61,000) were diagnosed with ADHD at some point as an adult. Individuals with ADHD were nine times as likely to suffer from depression as were adults not diagnosed with ADHD. They were also more than nine times as likely to suffer from anxiety or a substance use disorder, and twenty times as likely to be diagnosed with bipolar disorder. These findings are very consistent with reports from clinical samples in the USA and Europe.

Adults with ADHD also had elevated levels of metabolic disorders, being almost twice as likely to have high blood pressure, and more than twice as likely to have type 2 diabetes. Persons with ADHD but without psychiatric comorbidities were also almost twice as likely to have high blood pressure, and more than twice as likely to have type 2 diabetes.
Similar patterns were found in men and women with ADHD, although comorbid depression, bipolar disorder, and anxiety were moderately more prevalent in females than in males, whereas substance use disorder, type 2 diabetes, and hypertension were more prevalent in males than in females.

ADHD was less than a third as prevalent in the over-50 population as in the general adult population. Nevertheless, individuals in this older group with ADHD were twelve times as likely to suffer from depression, anxiety, or substance use disorders, and more than 23 times as likely to be diagnosed with bipolar disorder as their non-ADHD peers. They were also 63% more likely to have high blood pressure, and 72% more likely to have type 2 diabetes.

The authors noted, “Although the mechanisms underlying these associations are not well understood, we know from both epidemiologic and molecular genetic studies that a shared genetic predisposition might account for the co¬existence of two or more psychiatric conditions. In addition, individuals with ADHD may experience increased difficulties as the demands of life increase, which may contribute to the development of depression and anxiety.” As for associations with hypertension and type 2 diabetes, these “might reflect health ¬risk behaviors among adult patients with comorbid ADHD in addition to a shared biological substrate. As others have noted, inattention, disinhibition, and disorganization associated with ADHD could make it difficult for patients to adhere to treatment regimens for metabolic disorders.” They concluded that “Clinicians should remain vigilant for a wide range of psychiatric and metabolic problems in ADHD affected adults of all ages and both sexes.”

Qi Chen, Catharina A. Hartman, Jan Haavik, Jaanus Harro, Kari Klungsøyr, Tor¬Arne Hegvik, Rob Wanders, Cæcilie Ottosen, Søren Dalsgaard, Stephen V. Faraone, Henrik Larsson, “Common psychiatric and metabolic comorbidity of adult attention-deficit/hyperactivity disorder: A population-based cross-sectional study,” PLoS ONE (2018), 13(9): e0204516.

Stephen V. Faraone, PhDA working group of the International League Against Epilepsy (ILAE), consisting of twenty experts spanning the globe (U.S., U.K., France, Germany, Japan, India, South Africa, Kenya, Brazil), recently published a “consensus paper” summarizing and evaluating what is currently known about comorbid epilepsy with ADHD, and best practices.

ADHD is two to five times more prevalent among children with epilepsy. The authors suggest that ADHD is underdiagnosed in children with epilepsy because its symptoms are often attributed either to epilepsy itself, or to the effects of antiepileptic drugs (AEDs).

The working group did a systematic search of the English-language research literature. It then reached consensus on practice recommendations, graded on the strength of the evidence.

Three recommendations were graded A, indicating they are well-established by evidence:

  • Children with epilepsy with comorbid intellectual and developmental disabilities are at increased risk of ADHD.
  • There is no increased risk of ADHD in boys with epilepsy compared to girls with epilepsy.
  • The anticonvulsant valproate can exacerbate attentional issues in children with childhood absence epilepsy (absence seizures look like staring spells during which the child is not aware or responsive). Moreover, a single high-quality population-based study indicates that valproate use during pregnancy is associated with inattentiveness and hyperactivity in offspring.

Four more were graded B, meaning they are probably useful/predictive:

  • Poor seizure control is associated with increased risk of ADHD.
  • Data support the ability of the Strengths and Difficulties Questionnaire (SDQ) to predict ADHD diagnosis in children with epilepsy: “Borderline or abnormal SDQ total scores are highly correlated with the presence of a validated psychiatric diagnosis (93.6%), of which ADHD is the most common (31.7%).” The SDQ can therefore be useful as a screening tool.
  • Evidence supports the efficacy of methylphenidate in children with epilepsy and comorbid ADHD.
  • Methylphenidate is tolerated in children with epilepsy.

At the C level of being possibly useful, there is limited evidence that supports that atomoxetine is tolerated in children with ADHD and epilepsy, and that the combined use of drugs for ADHD and epilepsy (polytherapy) is more likely to be associated with behavioral problems than monotherapy. In the latter instance, “Studies are needed to elucidate whether the polytherapy itself has resulted in the behavioral problems, or the combination of polytherapy and the underlying brain problem reflects difficult‐to‐control epilepsy, which, in turn, has resulted in the prescription of polytherapy.”

All other recommendations were graded U (for Unproven), “Data inadequate or conflicting; treatment, test or predictor unproven.” These included three where the evidence is ambiguous or insufficient:

  • Evidence is conflicted for the impact of early seizure onset on the development of ADHD in children with epilepsy.
  • Tolerability for amphetamine in children with epilepsy is not defined.
  • Limited evidence exists for the efficacy of atomoxetine and amphetamines in children with epilepsy and ADHD.

There were also nine U-graded recommendations based solely on expert opinion. Most notable among these:

  • Screening children with epilepsy for ADHD beginning at age 6.
  • Reevaluation of attention function after any change in antiepileptic drug.
  • Screening should not be done within 48 hours following a seizure.
  • ADHD should be distinguished from childhood absence epilepsy based on history and an EEG with hyperventilation.
  • Multidisciplinary involvement in transition and adult ADHD clinics is essential as many patients experience challenges with housing, employment, relationships, and psychosocial well‐being.

Stéphane Auvin et al., “Systematic review of the screening, diagnosis, and management of ADHD in children with epilepsy. Consensus paper of the Task Force on Comorbidities of the ILAE Pediatric Commission,” Epilepsia (2018), doi: 10.1111/epi.14549. [Epub ahead of print].


Stephen V. Faraone, PhDA Norwegian team based at the University of Bergen recently performed a population study using the country’s detailed national health registries. With records from more than two and a half million Norwegians, the team examined what, if any, associations could be found between ADHD and nine autoimmune diseases: ankylosing spondylitis, Crohn’s disease, iridocyclitis, multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes, and ulcerative colitis.

After adjusting for age and maternal education, the team found no association between ADHD and five of the nine autoimmune disorders: type 1 diabetes, rheumatoid arthritis, iridocyclitis, systemic lupus erythematosus, and multiple sclerosis. In the case of ankylosing spondylitis, it found no association with males with ADHD, but a negative association with females. Females with ADHD were less likely to have ankylosing spondylitis. The adjusted odds ratio (aOR) was 0.56 (95% CI 0.32-0.96).

Positive associations were found for only three autoimmune diseases. The strongest was for psoriasis, with adjusted odds ratios of 1.6 (95% CI 1.5-1.7) for females and 1.3 (95% CI 1.2-1.4) for males. When further adjusted for education, smoking, and body mass index (BMI), however, the adjusted odds ratio for females with ADHD dropped to 1.3 (95% CI 1.0-1.6).

The second strongest association was with Crohn’s disease. But here it was only among women. The odds ratio in this case was 1.4 (95% CI 1.2-1.8). Males with ADHD were actually less likely to have Crohn’s disease, with an odds ratio of 0.71 (95% CI 0.54-0.92).

Finally, females with ADHD were slightly more likely to have ulcerative colitis, with a barely significant odds ratio of 1.3 (95% CI 1.1-1.5), while no such association was found for males with ADHD, whose odds ratio was a statistically nonsignificant 0.9.

Given the large sample size of over two and a half million, this is no underpowered study. It found no association between ADHD and the generic category of autoimmune disorders. Furthermore, it is a stretch to argue that there are any clear and clinically meaningful links between ADHD and any of the specific disorders that were analyzed in this study. The small and often opposite effect sizes may simply reflect limitations with the data (presumed autoimmune disorders were identified based on drugs prescribed), or to other unidentified confounding factors.

Tor‐Arne Hegvik, Johanne Telnes Instanes, Jan Haavik, Kari Klungsøyr, Anders Engeland, “Associations between attention‐deficit/hyperactivity disorder and autoimmune diseases are modified by sex: a population‐based cross‐sectional study,” European Child & Adolescent Psychiatry, vol. 27 (2018), 663-675.

Stephen V. Faraone, PhDAn international team of researchers has carefully examined the best current evidence and found strong evidence for an association between asthma and ADHD by combining a meta-analysis of prior data with a new analysis of the Swedish population.

The meta-analysis identified 46 datasets with a total of more than 3.3 million persons. It computed an unadjusted odds ratio (OR) of 1.7, which indicates that ADHD patients have about twice the risk of developing asthma compared with people without ADHD. Limiting the meta-analysis to studies that adjusted for confounding factors, 30 datasets with more than a third of a million participants still led to an adjusted odds ratio of 1.5 (95% CI 1.4 – 1.7). The likelihood of obtaining this result by chance in such a large sample would be less than one in ten thousand.

When the team further checked this result against the results for the Swedish population ofmore than one and a half million persons, the odds ratio was an almost identical 1.6. Adjusting for confounding factors reduced it to 1.5 (95% CI 1.41 – 1.48). That means the findings are very robust: asthma and ADHD are associated, with an odds ratio of 1.5, after adjusting for confounding factors.

What does this small but statistically very reliable association between asthma and ADHD mean? For researchers, it suggests that the two disorders may have common risk factors and that the search for these shared risk factors might lead to improved treatments. These risk factors might also be shared with two other somatic conditions for which ADHD patients are at increased risk: obesity and eczema. It is possible that common inflammatory processes account for this overlap among disorders. Clinicians should be aware that children with asthma have an increased risk for ADHD, although given the small association, systematic screening may not be warranted. But given that ADHD might interfere with asthma medication compliance, the disorder should be considered among noncompliant youth, especially those who show other evidence of inattention, poor memory or disorganization.

Samuele Cortese, Shihua Sun, Junhua Zhang, Esha Sharma, Zheng Chang, Ralf Kuja-Halkola, Catarina Almqvist, Henrik Larsson, Stephen V Faraone, “Association between attention deficit hyperactivity disorder and asthma: a systematic review and meta-analysis and a Swedish population-based study,” Lancet Psychiatry, Published online July 24, 2018.

This article provides a review of the cardiovascular effects of ADHD medications including potential effects on blood pressure, heart rate and risk of cardiovascular events (myocardial infarction, sudden death and stroke).

The article notes that meta-analyses have generally found that the effects of stimulant medications and atomoxetine were generally similar on systolic blood pressure (1-3 mm Hg) and heart rate (2-5 beats/minute); these were felt to be of limited clinical significance, except for patients with elevated blood pressures or heart rate antecedent to starting these ADHD therapies. However, as these are average changes, changes in individual patients may vary and important to monitor. Additionally, the meta-analysis and observational data available also do not find significantly higher risks for MI or stroke in patients receiving stimulant medications. These findings are complicated by the use of clinical trial data in the meta-analysis which specifically limit is the enrollment of patients with higher risks of pre-existing cardiovascular illnesses and the observational data were of relatively short treatment exposures.

This article is important for clinicians because it reviews the cardiovascular safety profiles of current ADHD medications and also recommends monitoring of blood pressure and pulse at baseline and during treatment. Furthermore, the authors recommend baseline screening patients for significant cardiovascular histories via family history of cardiovascular disease and sudden death.


Stephen V. Faraone, PhDAn international group of twelve experts recently published a consensus report examining the state of the evidence and offering recommendations to guide screening, diagnosis, and treatment of individuals with ADHD-SUD comorbidity.[1]

In a clear sign that we are still in the early stages of understanding this relationship, five of the thirteen recommendations received the lowest recommendation grade (D), eight received the next-lowest (C), and none received the highest (A and B). The lower grades reflected the absence of the highest level of evidence, obtained from meta-analyses or systematic reviews of relevant randomized controlled trials (RCTs).

Nevertheless, with these limitations in mind, the experts agreed on the following points:


  • The strongest recommendation, the only one based on a 2+ level of evidence (well-conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal) is that the “Short Version of the Adult ADHD Self-Report Scale (ASRS-SV) screener is currently the most widely used and investigated screening tool in individuals with ADHD and comorbid SUD, with good sensitivity and specificity across studies.”
  • Two other recommendations were graded C: The diagnostic process should include current and past substance abuse and seek to involve partners and relatives in evaluating symptoms and functional impairments.
  • Four recommendations got the lowest grade, D. The experts suggested starting the diagnostic process as soon as possible and focusing on drug- and alcohol-free periods in the patient’s life during history taking. They also recommended that physicians and clinical psychologists should only make diagnoses if they have extensive training in diagnosing ADHD, as well as experience with adults with ADHD and with addiction care, and that they should consider treating adults with sufficiently severe ADHD symptoms.


  • In general, evidence was stronger in this area, and only one of the six recommendations was graded D. The other five recommendations were graded C, with the highest level of evidence being 2 (cohort or case and control studies with undetermined risk of bias), although in three cases it was level 3 (non-analytical studies, such as case reports and case series).
  • The grade D recommendation was to always consider a combination of psychotherapy and pharmacotherapy.

The grade C recommendations included considering adequate medical treatment of both ADHD and SUD; integrating ADHD treatment with SUD treatment as soon as possible;
considering psychotherapy targeting both; use of long-acting methylphenidate, extended-release amphetamines, and atomoxetine because of their low potential for abuse; and careful clinical management to avoid abuse and diversion of prescribed stimulants.

[1] Cleo L. Crunelle at al., “International Consensus Statement on Screening, Diagnosis and Treatment of Substance Use Disorder Patients with Comorbid Attention Deficit/Hyperactivity Disorder,” European Addiction Research, published online March 6, 2018, DOI: 10.1159/000487767.

ADHD Affects the Efficacy of Treatment for Eating Disorders in Adult Women

Stephen V. Faraone, PhDSwedish researchers examined outcomes for adult women who sought treatment at the Stockholm Centre for Eating Disorders over a period of two years and nine months. Out of 1,517 women who came to the clinic 1,143 remained eligible for the study, after excluding women whose symptoms did not fulfill the DSM-IV criteria for eating disorders or had incomplete records.

Of these, seven hundred patients could not be reached or declined to participate, leaving 443 for follow-up. To guard against the possibility that the follow-up group might not be representative of the overall treatment group, researchers compared age, body mass index, and scores on tests for depression, anxiety, compulsivity, inattention, and hyperactivity. The only statistically significant differences were small ones. The median age of the group lost to follow-up was one year younger, they were less likely to be living alone, and on average scored a single point higher on the depression test. Otherwise they were broadly similar.

The one-year follow-up on the study group found a substantial difference in rate of recovery from eating disorders between those wEating disorders and ADHDith and without comorbid ADHD. Almost three out of four patients (72%) who scored lower (between 0-17) on the World Health Organization adult ADHD self-report scale had recovered from their eating disorder. Among those scoring 18 and higher, on the other hand, it was less than half (47%). This difference was extraordinarily unlikely (one chance in one thousand) to be due to chance (p=.001).

Another way of expressing this is through odds ratios. Those scoring 18 and up on the ADHD self-report scale were about two and a half times less likely to recover from their eating disorders following treatment. More specifically, they were about three times less likely to recover from loss of control and binging, and almost three and a half times less likely to recover from purging.

To improve outcomes, the researchers suggest “identifying concomitant ADHD symptoms and customizing treatment interventions based on this.” They specifically propose controlled clinical trials to explore the effect of combining stimulant medications with standard treatment for eating disorders.

Nils Erik Svedlund, Claes Norring, Ylva Ginsberg, Yvonne von Hausswolff‐Juhlin, “Are treatment results for eating disorders affected by ADHD symptoms? A one‐year follow‐up of adult females,” European Eating Disorders Review (2018).