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.

REFERENCES
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.

Mindfulness has been defined as “intentionally directing attention to present moment experiences with an attitude of curiosity and acceptance.” Mindfulness-based interventions (MBIs) aim to improve mindfulness skills.

A newly-published meta-analysis of randomized controlled trials (RCTs) by a team of British neurologists and psychiatrists explores the effectiveness of MBIs in treating a variety of mental health conditions in children and adolescents. Among those conditions is the attention deficit component of ADHD.

A comprehensive literature search identified studies that met the following criteria:

  1. The effects of mindfulness were compared against a control condition – either no contact, waitlist, active, or attention placebo. Waitlist means the control group receives the same treatment after the study concludes. Active control means that a known, effective treatment (as opposed to a placebo) is compared to an experimental treatment. Attention placebo means that controls receive a treatment that mimics the time and attention received by the treatment group but is believed not to have a specific effect upon the subjects. Participants were randomly assigned to the control condition.
  2. The MBI was delivered in more than one session by a trained mindfulness teacher, involved sustained meditation practice, and it was not mixed in with another activity such as yoga.

Eight studies evaluating attention deficit symptoms, with a combined total of 1,158 participants, met inclusion criteria. The standardized mean difference (SMD) was 0.19, with a 95% confidence range of 0.04 to 0.34 (p = .02). That indicates a small effect size for MBIs in reducing attention deficit symptoms. Heterogeneity was low (I2 = 35, p = .15), and the Egger test showed little sign of publication bias (p = 0.42).

When looking only at studies with active controls, five studies with a total of 787 participants yielded an SMD of 0.13, with a 95% confidence interval of -0.01 to 0.28 (p = .06), indicating a tiny effect size that failed to reach significance. Active controls most commonly received health education, with a few receiving social responsibility trainings or Hatha yoga.

Overall, this meta-analysis suggests limited effectiveness, especially when compared with active controls. If MBIs are effective for ADHD, there effect on symptoms is very small. Thus, such treatments should not be used in place of the many well-validated, evidenced-based therapies available. Whether longer periods of MBI (training times varied between 2 and 18 hours spread out over 2 to 24 weeks) might result in greater effect sizes remains unexplored.

REFERENCES
Darren L. Dunning, Kirsty Griffiths, Willem Kuyken, Catherine Crane, Lucy Foulkes, Jenna Parker, and Tim Dalgleish, “Research Review: The effects of mindfulness-based interventions on cognition and mental health in children and adolescents – a meta-analysis of randomized controlled trials,” Journal of Child Psychology and Psychiatry (2018), doi:10.1111/jcpp.12980.

A newly-published systematic review by a British team identified 48 qualitative and quantitative studies that explored “ADHD in primary care, including beliefs, understanding, attitudes, and experiences.” The studies described primary care experiences in the U.S., Canada, Europe, Australia, Singapore, Iran, Pakistan, Brazil, and South Africa.

More than three out of four studies identified deficits in education about ADHD. Of particular concern was the training of primary care providers (PCPs), most of whom received no specific training on ADHD. In most places, a quarter or less of PCPs received such training. Even when such training was provided, PCPs often rated it as inadequate, and said they did not feel they could adequately evaluate children with ADHD. There was even less training for adult ADHD.

A 2009 survey of 194 PCPs in Pakistan found that ADHD was not included at all in medical training there, and that most learned from colleagues. Half readily admitted to having no competence, and less than one in five were shown to have adequate knowledge about ADHD. In a 2009 survey of 229 South African PCPs, only 7 percent reported adequate training in childhood ADHD, and a scant one percent in adult ADHD.

These problems were by no means limited to less developed countries. A 2001 U.K. survey of 150 general practitioners found that only 6 percent of them had received formal ADHD training. In a 2002 study of 499 Finnish PCPs, only half felt confident in their ability to diagnose ADHD. A 2005 survey of 405 Canadian PCPs likewise found that only half reported skill and comfort in diagnosis. In a 2009 survey of 400 U.S. primary care physicians, only 13 percent said they had received adequate training. A 2017 study of Swiss PCPs found that only five of the 75 physicians in the sample expressed competence in diagnosis.

Eight studies explored knowledge of DSM (Diagnostic and Statistical Manual of Mental Disorders) criteria and clinical guidelines among PCPs. Only a quarter of PCPs were using DSM criteria, and only one in five were using published guidelines. In a 1999 survey of 401 pediatricians in the U.S. and Canada, only 38 percent reported using DSM criteria. A 2004 survey of 723 U.S. PCPs found only 44 percent used DSM criteria. In a 2006 UK study of 40 general practitioners, only 22 percent were aware of ADHD criteria. In the same year, a survey of 235 U.S. physicians found that only 22 percent were familiar with ADHD guidelines, and 70 percent used child behavior in the office to make a diagnosis. More encouragingly, a 2010 U.S. study reported that use of APA (American Psychological Association) guidelines by PCPs had expanded markedly between 1999 and 2005, from one in eight to one in two.

Given these facts, it is unsurprising that many PCPs expressed lack of confidence in treating ADHD. In a 2003 survey of 143 South African general practitioners, two thirds thought it was difficult to diagnose ADHD in college students. A 2012 U.S. study of 1,216 PCPs found that roughly a third lacked confidence in diagnosis and treatment. More than a third said they did not know how to manage adult ADHD. In a 2015 survey of 59 physicians and 138 nurses in the U.S., half lacked confidence in their ability to recognize ADHD symptoms. This was especially pronounced among the nurses. A 2001 U.K. survey of 150 general practitioners found that nine out of ten wanted further training in drug treatment, and more than one out of ten were unwilling to prescribe due to insufficient knowledge.

Misconceptions about ADHD were widespread. In a survey of 380 U.S. PCPs, almost half thought ADHD medications were addictive, one in five thought ADHD was “caused by poor diet,” more than one in seven thought “the child does it on purpose,” and one in ten thought medications can cure ADHD. Some studies reported that many PCPs believed ADHD was related to consumption of sugary food and drink. Others reported a gender bias. A 2002 U.S. study of 395 PCPs found that when presented with boys and girls with parent reported problems, they were significantly more likely to diagnose ADHD in boys.

A 2010 Iranian study of 665 PCPs found that 82 percent believed children adopted ADHD behavior patterns as a strategy to avoid obeying rules and doing assignments. One third believed sugary food and drink contributed to ADHD. Only 6 percent believed it could be a lifelong condition. Half blamed dysfunctional families. The aforementioned large 2012 U.S. study similarly found that almost half of PCPs believed ADHD was caused by absent or bad parenting. More than half of 399 Australian PCPs surveyed in 2002 believed inadequate parenting played a key role. In a 2003 study of 48 general practitioners in Singapore, a quarter blamed sugar for ADHD. A 2014 survey of 57 French pediatricians found that a quarter thought ADHD was a foreign construct imported into France, and 15 percent attributed it to bad parenting.

In all, ten studies reported a widespread belief that ADHD was due to bad parenting, with ratios varying from over one in seven PCPs to more than half. They were particularly likely to attribute hyperactivity to dysfunctional families, and to dismiss parents’ views of hyperactivity as a medical problem as a way to deflect attention from inadequate parenting.

While a third of the studies reported on stigma, the surprise was that it did not seem to play as big a role as expected. A 2012 study in the Netherlands found that 74 physicians and 154 non-medical professionals matched by age, sex, and education showed no differences in level of stigmatization toward ADHD.

On the other hand, the studies identified significant resource constraints limiting more effective understanding, diagnosis, and treatment. Given the complex nature of ADHD, the time required to gain relevant information, especially in the context of competing demands on the attention of PCPs, was a limiting factor. Many studies identified a need for better assessment tools, especially for adults.

Another major constraint was PCP uneasiness about medication. Studies found a widespread lack of knowledge about treatment options, and more specifically the pros and cons of medication relative to other options. This often led to an unwillingness to prescribe.

Yet another limitation was difficulties PCPs had in communicating with mental health specialists. One study found that less than one in six PCPs received communications from psychiatrists. Much of this was ascribed to “system failure”: discontinuity of care, no central accountability, limited resources, buck passing. Many PCPs were unsure who to turn to.

Another problem is in often faulty interactions between schools, parents, children, and providers. Parents often fail to keep appointments. Schools and parents often are less than cooperative in providing information. In a 2004 survey of 786 U.S. school nurses, less than half reported good levels of communication between schools and physicians. Schools and parents often apply pressure on PCPs to issue a diagnosis. In a U.S. survey of 723 PCPs, more than half reported strong pressure from teachers to diagnose ADHD, and more than two-thirds said they were under pressure to prescribe medication.

The authors noted, “The need for education was the most highly endorsed factor overall, with PCPs reporting a general lack of education on ADHD. This need for education was observed on a worldwide scale; this factor was discussed in over 75% of our studies, in 12 different countries, suggesting that lack of education and inadequate education was the main barrier to understanding of ADHD in primary care.”

In addition, “time and financial constraints affect the opportunities for PCPs to seek extra training and education but also affect the communication with other professionals such as secondary care workers, teachers and parents.”

The authors cautioned that only eleven of the 48 studies were published since 2010. Also, because it was a systematic review and not a meta-analysis, there was no way to evaluate publication bias.

They concluded, “Better training of PCPs on ADHD is, therefore, necessary but to facilitate this, dedicated time and resources towards education needs to be put in place by service provider and local authorities.”

REFERENCES
B. French, K. Sayal, D. Daley, “Barriers and facilitators to understanding of ADHD in primary care: a mixed‐method systematic review,” European Child & Adolescent Psychiatry (2018), https://doi.org/10.1007/s00787-018-1256-3.

Michael J. Silverstein , Stephen V. Faraone, Terry L. Leon, Joseph Biederman, Thomas J. Spencer, and Lenard A. Adler

Journal of Attention Disorders. 1–11: 2018. DOI: 10.1177/1087054718804347

Lenard Adler, MD ADHD in AdultsThe Diagnostic and Statistical Manual of Mental Disorders (5th ed.) (DSM-5) still defines ADHD symptoms in terms nine inattentive (IA) and nine hyperactive-impulsive (H-I) symptoms, to form the core eighteen symptoms of the disorder; this is in spite of a large literature that indicates that higher level symptoms of organization, planning and prioritization known as Executive Function Deficits (EFDs) common co-travel with symptoms of ADHD and are highly impairing to adults with ADHD. The investigators examined the relationship of core ADHD IA and HI symptoms and EFDs and the predictive utility of the Adult ADHD Investigator Symptom Rating Scale (AISRS) in identifying those with adult ADHD and Executive Dysfunction (ED). The AISRS is a clinician-administered, severity based (0-3), semistructured interview, containing adult ADHD specific prompts, developed to evaluate ADHD symptoms at baseline and during treatment. The Adult ADHD Self-Report Scale (ASRS) Symptom Checklist was also administered. Both the AISRS and ASRS Symptom Checklist were expanded to not only include the 18 core DSM-5 symptoms of ADHD, but also nine additional symptoms of EFD and four symptoms of Emotional Dyscontrol (EC). Executive Function was also assessed via the BRIEF-A, a well-normed scale to assess EF, with patients with global executive complex (GEC) T scores T >= 65 (1.5 standard deviations above the mean, 93 percentile) being indicative of ED. Subjects were recruited from referrals to a university adult ADHD program or a primary care clinical practice; 297 subjects participated (171 with adult ADHD). (IA) and (H-I) symptoms on the AISRS and ASRS Symptom Checklist were moderately to strongly correlated with and highly predictive of EFDs (with correlations being stronger for IA symptoms). Receiver operating characteristic curve analysis showed that an AISRS DSM 18-item score of ⩾ = 28 was most predictive of clinical ED. This study is to clinicians because it highlights the importance of assessing EFDs in addition to core symptoms of IA and HI when evaluating patients with adult ADHD.

Rachael Morkem, Scott Patten, John Queenan, and David Barber

Journal of Attention Disorders 1 –8 , 2017 DOI: 10.1177/1087054717720719

This study describes trends the incidence and prevalence of prescribing ADHD medication in a large Canadian Primary Care Physician (PCP) Network over a ten year period from 2005-2015. Canada has public funded health care, creating a system that the provision for chronic disorders (such as ADHD) is often provided by PCPs, who serve as gatekeepers to specialty referrals only when necessary. A population-based retrospective cohort was derived from EMR data from the Canadian Primary Care Sentinel Surveillance Network, which has 11 practice-based research networks (PBRNs) composed of 1,100 primary care practitioners throughout Canada. Total number of prescriptions, type of medication, age group were assessed by year throughout the ten-year span. The annual prevalence was determined by establishing the number of patients prescribed at least one ADHD medication, divided by total number of patients with a PCP visit that year. Annual incidence rates were established using a similar formula for patients who were receiving their initial treatment with ADHD medication. The authors found over the decade a 2.5 and 2.6 fold increase in the prescribing prevalence in preschool and school age children, respectively and a 4 fold increase in prescribing prevalence in adults. Methylphenidate was the most commonly prescribed medication over the decade (65%), with a slight decrease in the later years of the decade, presumably due to the introduction of the long-acting amphetamine lisdexamphetamine. The authors noted that although ADHD disease prevalence was stable, the prescribing prevalence was increasing over the decade. Also gender differences of higher prescribing rates of boys:girls in children and adolescents were not seen in adults. The investigators posit that since the ADHD disease prevalence was noted to be relatively stable in Canada (Hauck et al. 2017), and the frequency of medication prescription remains below ADHD prevalence, the increased prevalence of prescriptions may reflect improved long-term treatment. Several caveats should be noted to this study: 1) the most common annual frequencies of taking medications were in the 20% range for once or >=10/year; this bimodal distribution may indicate ongoing issues with adherence to medications in Canadanian ADHD patients, 2) the authors were unclear as to how they handled patients who switched between medication preparations and 3) as the authors note, the study is only able to examine what was prescribed, but not what was taken. One take home point for US clinicians is the higher utilization of methylphenidate products in the Canadian population as compared to what has been described in US adult ADHD populations.

REFERENCES:
Hauck, T. S., Lau, C., Wing, L. L. F., Kurdyak, P., & Tu, K. (2017). ADHD treatment in primary care: Demographic factors, medication trends, and treatment predictors. Canadian Journal of Psychiatry, 62, 393-402.

Yan He, Jian Chen, Li-Hua Zhu, Ling-Ling Hua, and Fang-Fang Ke

Journal of Attention Disorders 1 –11 , 2017 DOI: 10.1177/1087054717696766

This article describes a meta-analyses of studies which examined the potential effects of maternal smoking on the risk of childhood ADHD. A prior meta-analysis in 2005 (Langley, Rice, Van den Bree, & Thapar, 2005) found a strong association between maternal smoking and subsequent development of childhood ADHD in exposed offspring. Several recent individual studies also found an association be, tween maternal smoking and childhood ADHD, but one prospective study (Ball et al., 2010) did not find such an association. Therefore, given the length of time since the last meta-analysis and the one negative study noted above, highlighted the need for an updated meta-analysis. The authors employed fairly standard meta-analysis guidelines via the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement, which included a selection of studies, data extraction and assessment of study quality. The risk ratios (RRs) and 95% CIs reported in the individual studies were pooled across studies to examine the potential association of maternal smoking during pregnancy and childhood ADHD risk. The authors also examined for presence of publication bias and changing association over time. 265 studies were originally identified, with 12 meeting the stringent criteria to be included in the meta-analysis. The main finding of the analysis was the maternal smoking was modestly association with an increased risk of ADHD in children (pooled RR = 1.58, 95% CI = [1.33, 1.88]) and this association seemed to increase over time (by examining publication year); no significant publication bias was seen. The authors that the association they observed was not as robust as the one seen by Langley et al. for several reasons: their including a larger number of trials, which were limited to those with prospective and not case-controlled desi This meta-analysis is important for clinicians as it highlights the importance of the need to caution their patients as to potential risks of offspring developing ADHD in mothers who smoke during pregnancy.

REFERENCES:
Ball, S. W., Gilman, S. E., Mick, E., Fitzmaurice, G., Ganz, M. L., Seidman, L. J., & Buka, S. L. (2010). Revisiting the association between maternal smoking during pregnancy and ADHD. Journal of Psychiatric Research, 44, 1058-10

Langley, K., Rice, F., Van den Bree, M. B., & Thapar, A. (2005). Maternal smoking during pregnancy as an environmental risk factor for attention deficit hyperactivity disorder behaviour. A review. Minerva Pediatrica, 57, 359-37

Stephen V. Faraone, Michael J. Silverstein , Kevin Antshel, Joseph Biederman, David W. Goodman, Oren Mason, Andrew A. Nierenberg, Anthony Rostain, Mark A. Stein and Lenard A. Adler

Journal of Attention Disorders, 1–15, 2018, DOI: 10.1177/1087054718804354

Lenard Adler, MD ADHD in AdultsThis manuscript reviews the results of the first phase of Quality Measures (QM) Initiative of the American Professional Society of ADHD and Related Disorders (APSARD). QMs (sometimes described as Quality Indicators) are critical metrics to the delivery and assessment of state-of-the-art health care; QMs numerically describe outcomes, patient perceptions, processes quantify health care processes, outcomes, patient perceptions, and systems. The authors followed the pathway outlined by the U.S. Agency for Healthcare Research and Quality (AHRQ) for the development of QMs; the manuscript describes the first phase, the development of draft QMs. This was a four-step process: 1) a literature search for adult ADHD QMs; (2) having experts develop a “wide net” of potential QMs in the areas of screening, diagnosis, treatment, follow-up, care coordination, and patient experience; (3) cross-referencing this “wide-net” of QMs to existing adult ADHD guidelines; (4) have ADHD experts rate the importance, reliability, validity, feasibility, and usability of the QMs via an online survey. The top 10 QMs from the expert survey were: Screening: % high-risk patients screened (e.g., depressed patients, family history of ADHD), Diagnosis: % patients treated for ADHD having documented DSM-5 diagnosis of ADHD, % patients with ADHD with review of other psychiatric disorders, % patients with ADHD with documentation of impairment, Treatment initiation: % patients receiving ADHD medications for whom treatment alternatives, benefits and risks have been discussed, % patients with ADHD assessed for vitals prior to medication treatment, % patients with ADHD for whom warnings and contraindications for medication were reviewed, Treatment follow-up: % patients with ADHD where validated measure of symptom change used to assess treatment efficacy at least annually, % patients stabilized on an ADHD medication seen at least once per year, % patients prescribed medication for ADHD seen within 1 month of initial prescription. This manuscript is important for clinicians because it is the first step toward the development of QMs for adult ADHD, which have not existed to date; if validated through field testing in the second phase of the initiative, these QM may be important metrics of health care quality in the care of patients with ADHD.

Journal of Attention Disorders 1 –7 DOI: 10.1177/1087054718763736 journals.sagepub.com/home/jad

Benjamin J. Lovett and Alexander H. Jordan

Lenard Adler MD - ADHD in Adults FacultyRates of ADHD in college students have been increasing somewhat in recent years, as has use of screening tools to help identify individuals at risk for disorders such as ADHD. These investigators designed a trial to examine whether screening for adult ADHD, in essence creating some positive expectation bias of having the disorder in leading to increased reporting of ADHD symptoms and altered performance on cognitive tests. One group was screened for ADHD using the ASRS v.1.1 Screener and received feedback if they screened positive for the disorder and then completed a self ADHD symptom checklist (CAARS: S Long version) and a batter of psychological tests (three subtests on the Woodcock– Johnson IV Tests of Cognitive Abilities (WJ-IV) (processing speed), a mathematical test and Letter-Pattern Matching (LPM)/Number-Pattern Matching (NPM), and Pair Cancelation (PC) for general cognitive efficiency. The control group received the same interventions except were not screened for ADHD. There were no significant differences in the two groups in terms of ADHD symptoms or neuropsychological measures. The authors note that while there was concern that screening positive for ADHD might result in increased expectation of having more ADHD symptoms, these effects were limited and did not significantly affect reporting ADHD symptoms. Several limitations of the trial include the constraint of the sample to only college students which limits the generalizability of the results, the absence of a comparison intervention (ie. Mock screening) in the control group and the use of DSM-IV version of the adult ADHD screener, instead of the most recently validated DSM-5 version. The important take-home point for clinicians seeing college students is the lack of increased reporting of ADHD symptoms and absence of effects on neuropsychological tests introduced by the process of screening for ADHD.

Journal of Attention Disorders 1 –10 © The Author(s) DOI: 10.1177/1087054718787894 journals.sagepub.com/home/jad

Jessica R. Lunsford-Avery, Scott H. Kollins, and John T. Mitchell

Lenard Adler MD - ADHD in Adults FacultySluggish cognitive tempo is a constellation of symptoms including sluggishness, daydreaming, being slow to react, easily bored and fogginess in thinking, which has been shown to exist in several disorders, but commonly in children with ADHD (Barkley 2014). This investigation is important as the authors characterize the psychometric properties of self and collateral report of the Barkley SCT scale (BAARS-IV: SCT subscale – nine items) versus the Conners Adult ADHD Scale in 124 adults (80 of whom had ADHD). The Barkley SCT scale had high internal consistency (self-report Cronbach’s α = .79, collateral-report Cronbach’s α = .82). The self and collateral versions of the Barkley SCT scale were significantly, moderately correlated after covarying for age and sex (r = .41, p < .001). Factor analyses supported the same three factors generally found in studies of childhood SCT: Slow/Daydreamy, Sleepy/Sluggish and Low Initiation/Persistence Symptoms. The Barkley SCT scale was fairly highly correlated with ADHD symptoms in the CAARS, except for the Sleepy/Sluggish factor not correlating with Hyperactivity/Restlessness or Impulsivity and lower association with Emotional Lability. The lack of association of the Sleepy/Sluggish factor with Restlessness and Impulsivity appears to have some face validity given the differential nature of the symptoms. This article is important to clinicians because it highlights the importance of assessing adult ADHD patients for symptoms of sluggish cognitive tempo and how these SCT symptoms may relate to DSM-5 ADHD symptoms.

REFERENCES
Barkley, R. A. (2014). Sluggish cognitive tempo (concentration deficit disorder?): Current status, future directions, and a plea to change the name. Journal of Abnormal Child Psychology, 42, 117-125. doi:10.1007/s10802-013-9824-y

Our genes are very important for the development of mental disorders – including ADHD, where genetic factors capture up to 75% of the risk. Until now, the search for these genes had yet to deliver clear results. In the 1990s, many of us were searching for genes that increased the risk for ADHD because we know from twin studies that ADHD had a robust genetic component. Because I realized that solving this problem required many DNA samples from people with and without ADHD, I created the ADHD Molecular Genetics Network, funded by the US NIMH. We later joined forces with the Psychiatric Genomics Consortium (PTC) and the Danish iPSYCH group, which had access to many samples.

The result is a study of over 20,000 people with ADHD and 35,000 who do not suffer from it – finding twelve locations (loci) where people with a particular genetic variant have an increased risk of ADHD compared to those who do not have the variant. The results of the study have just been published in the scientific journal Nature Genetics, https://www.nature.com/articles/s41588-018-0269-7.

These genetic discoveries provide new insights into the biology behind developing ADHD. For example, some of the genes have significance for how brain cells communicate with each other, while others are important for cognitive functions such as language and learning.

We study used genomewide association study (GWAS) methodology because it allowed us to discover genetic loci anywhere on the genome. The method assays DNA variants throughout the genome and determines which variants are more common among ADHD vs. control participants. It also allowed for the discovery of loci having very small effects. That feature was essential because prior work suggested that, except for very rare cases, ADHD risk loci would individually have small effects.

The main findings are:

  1. A) we found 12 loci on the genome that we can be certain harbor DNA risk variants for ADHD. None of these loci were traditional ‘candidate genes’ for ADHD, i.e., genes involved in regulating neurotransmission systems that are affected by ADHD medications. Instead, these genes seem to be involved in the development of brain circuits.
  2. B) we found a significant polygenic etiology in our data, which means that there must be many loci (perhaps thousands) having variants that increase risk for ADHD. We will need to collect a much larger sample to find out which specific loci are involved;

We also compared the new results with those from a genetic study of continuous measures of ADHD symptoms in the general population. We found that the same genetic variants that give rise to an ADHD diagnosis also affect inattention and impulsivity in the general population. This supports prior clinical research suggesting that, like hypertension and hypercholesteremia, ADHD is a continuous trait in the population. These genetic data now show that the genetic susceptibility to ADHD is also a quantitative trait comprised of many, perhaps thousands, of DNA variants

The study also examined the genetic overlap with other disorders and traits in analyses that ask the questions: Do genetic risk variants for ADHD increase or decrease the likelihood a person will express other traits and disorders.  These analyses found a strong negative genetic correlation between ADHD and education. This tell us that many of the genetic variants which increase the risk for ADHD also make it more likely that persons will perform poorly in educational settings. The study also found a positive correlation between ADHD and obesity, increased BMI and type-2 diabetes, which is to say that variants that increase the risk of ADHD also increase the risk of overweight and type-2 diabetes in the population.

This work has laid the foundation for future work that will clarify how genetic risks combine with environmental risks to cause ADHD. When the pieces of that puzzle come together, researchers will be able to improve the diagnosis and treatment of ADHD.