What’s the Relationship Between Daytime Sleepiness and Cognitive Functioning in Adults with ADHD?

Stephen V. Faraone, PhD on March 16, 2020

Sleep disorders are one of the most commonly self-reported comorbidities of adults with ADHD, affecting 50 to 70 percent of them. A team of British researchers set out to see whether this association could be further confirmed with objective sleep measures, using cognitive function tests and electroencephalography (EEG).

Measured as theta/beta ratio, EEG slowing is a widely used indicator in ADHD research. While it occurs normally in non-ADHD adults at the conclusion of a day, during the day it signals excessive sleepiness, whether from obstructive sleep apnea or from neurodegenerative and neurodevelopmental disorders. Coffee reverses EEG slowing, as do ADHD stimulant medications.

Study participants were either on stable treatment with ADHD medication (stimulant or non-stimulant medication), or on no medication. Participants had to refrain from taking any stimulant medications for at least 48 hours prior to taking the tests. Persons with IQ below 80 or with recurrent depression or undergoing a depressive episode were excluded.

The team administered a cognitive function test, The Sustained Attention to Response Task (SART). Observers rated on-task sleepiness using videos from the cognitive testing sessions. They wired participants for EEG monitoring.

Observer-rated sleepiness was found to be moderately higher in the ADHD group than in controls. Although sleep quality was slightly lower in the sleepy group than in the ADHD group, and symptom severity slightly greater in the ADHD group than the sleepy group, neither difference was statistically significant, indicating extensive overlap.

Omission errors in the SART were strongly correlated with sleepiness level, and the strength of this correlation was independent of ADHD symptom severity. EEG slowing in all regions of the brain was more than 50 percent higher in the ADHD group than in the control group and was highest in the frontal cortex.

Treating the sleepy group as a third group, EEG slowing was highest for the ADHD group, followed closely by the sleepy group, and more distantly by the neurotypical group. The gaps between the ADHD and sleepy groups on the one hand, and the neurotypical group on the other, were both large and statistically significant, whereas the gap between the ADHD and sleepy groups was not. EEG slowing was both a significant predictor of ADHD and of ADHD symptom severity.

The authors concluded, “These findings indicate that the cognitive performance deficits routinely attributed to ADHD … are largely due to on-task sleepiness and not exclusively due to ADHD symptom severity. … we would like to propose a simple working hypothesis that daytime sleepiness plays a major role in cognitive functioning of adults with ADHD. … As adults with ADHD are more severely sleep-deprived compared to neurotypical control subjects and are more vulnerable to sleep deprivation, in various neurocognitive tasks they should manifest larger sleepiness-related reductions in cognitive performance. … One clear testable prediction of the working hypothesis would be that carefully controlling for sleepiness, time of day and/or individual circadian rhythms would result in substantial reduction in the neurocognitive deficits in replications of classic ADHD studies.”

REFERENCES:
Bartosz Helfer, Natali Bozhilova, Ruth E. Cooper, Joanna Ismene Douzenis, Stefanos Maltezos, Philip Asherson, “The Key Role of Daytime Sleepiness in Cognitive Functioning of Adults with ADHD,” European Psychiatry (2020), https://doi.org/10.1192/j.eurpsy.2020.28.

How effective are ADHD medications in adults with Autism Spectrum Disorder (ASD)?

Stephen V. Faraone, PhD on December 26, 2019

Autism spectrum disorder (ASD) is frequently comorbid with ADHD. Among adults with ADHD, as many as half are reported to also have ASD.

A Dutch team set out to answer two questions:

  1. Do adults with ADHD and comorbid ASD experience less effectiveness of pharmacological treatment for ADHD than adults with only ADHD?
  2. Do adults with ADHD and comorbid ASD experience different or more severe side effects of pharmacological treatment for ADHD than adults with only ADHD, as measured in side-effect scores, blood pressure, heart rate, and weight?

This was a retrospective study, using well-documented medical records, of the effects of drug treatment with methylphenidate (MPH), dexamphetamine (DEX), atomoxetine (ATX), bupropion, or modafinil.

The researchers compared 60 adults with comorbid ASD and ADHD to 226 adults with only ADHD. ADHD symptoms were scored using the Conners’ ADHD Rating Scale: Self Report–Short Version (CAARS: S-S). Side effects of ADHD medication were measured using either a 13-item or 20-item checklist with 4-point scales for item response. Researchers also tracked changes in body weight, blood pressure, and heart rate.

Following treatment, ADHD symptoms among the comorbid group declined by a quarter, and among the ADHD-only group by almost a third. There was no significant difference between men and women. Controlling for age, gender, and ADHD subtype, a comorbid diagnosis of ASD also did not significantly affect ADHD symptom reduction.

Turning to side effects, in the ADHD+ASD group, there were significant increases in decreased appetite and weight loss, and decreases in agitation, anxiety, and sadness/unhappiness. In the ADHD-only group, there were significant increases in decreased appetite, weight loss, and dry mouth, and decreases in sleeping disorder, nervousness, agitation, anxiety, and sadness / unhappiness. Yet there were no significant differences between the two groups. Side effects increased and decreased similarly in both. Likewise, there were no significant differences between the groups in changes in heart rate and blood pressure. The only significant difference in medication dosage was for bupropion, which was higher in the ADHD+ASD group, though without any sign of difference in side effects.

The authors concluded that this retrospective study “showed pharmacological treatment of adults with diagnoses of ADHD and ASD to be just as successful as the pharmacological treatment of adults with only ADHD,” but cautioned that “a randomized controlled trial should be conducted to evaluate the effectiveness and possible side effects of pharmacological treatment for ADHD in patients with ASD more reliably.”

REFERENCES
J. J. Muit, N. Bothof, and C. C. Kan, “Pharmacotherapy of ADHD in Adults With Autism Spectrum Disorder: Effectiveness and Side Effects,” Journal of Attention Disorders (2019) DOI: 10.1177/1087054719866255.

Long-Acting Liquid Methylphenidate for Treating ADHD in Intellectually Capable Adults with Autism Spectrum Disorder

Stephen V. Faraone, PhD on November 20, 2019

A team from Harvard Medical School and Massachusetts General Hospital conducted a six-week open-label trial of liquid-formulation extended-release methylphenidate (MPH-ER) to treat ADHD in adults with high-functioning autism spectrum disorder (HF-ASD). ASD is a lifelong disorder with deficits in social communication and interaction and restricted, repetitive behaviors. Roughly half of those diagnosed with ASD also are diagnosed with ADHD.

This was the first stimulant trial in adults with both ASD and ADHD. There were twelve male and three female participants, all with moderate to severe ADHD, and in their twenties, with IQ scores of at least 85.

Use of a liquid formulation enabled doses to be raised very gradually, starting with a daily dose of 5mg (1mL) and titrating up to 60mg over the first three weeks, then maintaining that level through the sixth week. Participants were reevaluated for ADHD symptoms every week during the six-week trial. Severity of ASD was assessed at the start, midpoint, and conclusion of the trial, as were other psychiatric symptoms.

Prior to the trial, researchers agreed on a combination of targets on two clinician-rated scoring systems that would have to be reached for treatment to be considered successful. One is a score of 2 or less on the CGI-S, a measure of illness severity, with scores ranging from 1 (normal, not at all ill) to 7 (most extremely ill). The other, a reduction of at least 30 percent in the AISRS score, which combines each of 18 symptoms of ADHD on a severity grid (0=not present; 3=severe; overall minimum score: 0; overall maximum score: 54).
At the conclusion of the trial, twelve of the fifteen patients (80 percent) met the preset conditions for success. Fully fourteen (93 percent) saw a ≥ 30 percent reduction in their AISRS score, while twelve scored ≤ 2 on illness severity.

However, when using the patient-rated ASRS scoring system, only five (33 percent) saw a ≥ 30 percent reduction in ADHD severity.

Thirteen participants (87 percent) reported at least one adverse event, and nine (60 percent) reported two or more. One reported a serious adverse event (attempted suicide) in a patient with multiple prior attempts. Because the attempt was not deemed due to medication they continued in and completed the trial. Seven participants experienced titration-limiting adverse events (headaches, palpitations, jaw pain, and insomnia). Headache was most frequent (53%), followed by insomnia and anxiety (33% each), and decreased appetite (27%).

During the trial, weight significantly decreased, while pulse significantly increased. There were no significant differences in other vital and cardiovascular measurements.

The authors concluded, “this OLT of short-term MPH-ER therapy documents that acute treatment with MPH-ER in young adults with ASD was associated with significant improvement in ADHD symptoms, mirroring the typically-expected magnitude of response observed in adults with only ADHD. Treatment with MPH-ER was well-tolerated, though associated with a higher than expected frequency of adverse events.”

They also cautioned, “The results of this study need to be considered in light of some methodological limitations. This was an open-label study; therefore, assessments were not blind to treatment. We did not employ a placebo control group and, therefore, cannot separate the effects of treatment from time or placebo effects. … firmer conclusions regarding the safety and efficacy of MPH-ER for the treatment of ADHD in HF-ASD populations await results from larger, randomized, placebo-controlled clinical trials.”

REFERENCES:
Gagan Joshi, Maura DiSalvo, Janet Wozniak, T. Atilla Ceranoglu, Amy Yule, Craig Surman, Ronna Fried, Maribel Galdo, Barbora Hoskova, Abigail Belser & Joseph Biederman, “A Prospective Open-Label Trial of Long-Acting Liquid Methylphenidate for the Treatment of Attention Deficit/Hyperactivity Disorder in Intellectually Capable Adults with Autism Spectrum Disorder,” The World Journal of Biological Psychiatry (2019) DOI: 10.1080/15622975.2019.1679392.

How Do Psychiatric Comorbidities Affect Risk of Premature Death Among Children and Adults with ADHD?

Stephen V. Faraone, PhD on August 6, 2019

The Nordic countries maintain detailed registers of their inhabitants. This enables researchers to examine patterns over entire nations. An international research team used the Swedish national registers for a prospective cohort study of 2,675,615 persons in the Medical Birth Register born in Sweden over a 27-year period from January 1, 1983 through December 31, 2009. Follow-up was completed in December 2013, with the oldest cohort member aged 31. The mean age at study entry was 6, and the mean at follow-up was 11.

Using personal identification numbers, researchers were able to cross-reference with the National Patient Register and the National Drug Register. From this they determined that 86,670 members of the cohort (3.2 percent) had ADHD, based either on records of clinical diagnosis or of prescription of ADHD drugs. Psychiatric comorbidities were likewise identified in the National Patient Register.

These comorbidities were significantly more prevalent in the ADHD population than in the rest of the cohort. For example, whereas only 2.2% of the non-ADHD group was diagnosed with substance use disorder (SUD), 13.3% of the ADHD group also had SUD, a six-fold difference. For depression it was a seven-fold difference, for schizophrenia a nine-fold difference.

The ADHD group had a significantly higher risk of premature death from all causes than the non-ADHD group, with an adjusted hazard ratio (HR) of 3.94 (95% CI 3.51-4.43). Unintentional injury (36%) and suicide (31%) were the leading causes of death in the ADHD group. Those with ADHD were more than eight times more likely to die by suicide than non-ADHD individuals, and roughly four times more likely to die from unintentional injury.

The vast majority of the increased risk appears to be associated with comorbid psychiatric conditions. Those with ADHD but no diagnosed comorbidities had an adjusted HR of 1.41 (95% CI 1.01-1.97). With a single comorbidity, the HR more than doubled to 3.71 (95% CI 2.88-4.78). With four or more comorbidities, it rose to a staggering 25.22 (95% CI 19.6-32.46).

The comorbid condition with the greatest impact was SUD, which increased the risk eight-fold by comparison with those with only ADHD (HR = 8.01, 95% CI 6.16-10.41). Anxiety disorder, schizophrenia, and personality disorder increased the risk about fourfold. Bipolar disorder, depression, and eating disorder increased risk roughly two and a half times.

Covariate analysis helped tease out what portion of the risk was associated with ADHD alone versus comorbid conditions. Adjusting for year of birth, sex, birth weight, maternal age at birth, parental educational level, and parental employment status, those with ADHD (including comorbid conditions) were 2.7 times more likely to prematurely die of natural causes than those without. Adjusting for comorbid psychiatric conditions completely eliminated the risk from ADHD alone (HR = 1.01, 95% CI .72-1.42).

Likewise, those with ADHD (including comorbid conditions) were six times as likely to die of unnatural causes. Adjusting for early-onset comorbid disorders (such as conduct disorders, autism spectrum disorder, and intellectual disability) only modestly reduced the HR to 5.3, but further adjusting for later-onset comorbid disorders (including substance use disorder, depressive disorder, bipolar disorder, anxiety disorder, schizophrenia, personality disorder, and eating disorders) reduced the HR to 1.57 (95% CI 1.35-1.83), and reduced it to insignificance in the case of suicide (HR = 1.13, 95% CI .88-1.45).

Summing up, the lion’s share of the greater risk of premature death in persons with ADHD is attributable to psychiatric comorbidities. Nevertheless, those with ADHD alone still face a 40 percent greater risk than those without ADHD.

The study did not examine effects of ADHD medication, which the authors state “should be analyzed because of documented potential benefits on ADHD symptoms and comorbid disorders.”

The authors concluded, “Among adults, early-onset psychiatric comorbidity contributed substantially to the premature mortality risks due to natural causes. On the other hand, later-onset psychiatric comorbidity, especially SUD, explained a substantial part of the risk for unnatural deaths, including all the risk of suicide deaths and most of the deaths due to unintentional injuries. These results suggest that overall health conditions and risk of psychiatric comorbidity should be evaluated clinically to identify high-risk groups among individuals with ADHD.”

REFERENCES:
Shihua Sun, MD; Ralf Kuja-Halkola, PhD; Stephen V. Faraone, PhD; Brian M. D’Onofrio, PhD; Søren Dalsgaard, PhD; Zheng Chang, PhD; Henrik Larsson, PhD, “Association of Psychiatric Comorbidity With the Risk of Premature Death Among Children and Adults With Attention-Deficit/Hyperactivity Disorder,” JAMA Psychiatry doi:10.1001/jamapsychiatry.2019.1944 Published online August 7, 2019.

Meta-analysis finds association between ADHD and suicidal behaviors

Stephen V. Faraone, PhD on June 26, 2019

A newly published meta-analysis of 57 studies encompassing almost a third of a million participants has uncovered a very strong association between ADHD and suicide, a strong association with suicidal ideation, and a small-to-medium association with suicide attempts.

The population examined included children, adolescents, and adults. Only persons formally diagnosed were considered to have ADHD. Studies that included self-injuries without suicidal intent were excluded. Most of the studies focused on European and American populations, with one in six from other locations, mostly Asian.

The most striking result was for actual suicides. The odds ratio (OR) for four datasets encompassing roughly one hundred forty thousand participants was 6.69 (95% CI 3.24 to 17.39, p < .0001). As a frame of reference, an OR of 1.5 is a small effect size, 2.5 a medium one, and 4.3 a large one. That means the effect size in this case is very large.

For suicidal ideation, 23 datasets with a combined total of just over 73,000 participants produced a medium-to-large OR of 3.5 (95% CI 2.94 to 4.25, p < .0001). In three datasets with more than nine thousand participants that adjusted for confounders, the adjusted OR was 4.5 (95% CI 1.72 to 11.63, p < .0001), indicating a large effect size.

For suicide attempts, 44 datasets encompassing over 228,000 participants produced an OR of 2.4 (95% CI 1.64 to 3.43, p < .0001). In six datasets with over 65,000 participants that adjusted for confounders, the adjusted OR dropped to 2.1 (95% CI 1.27 to 3.47, p = .005).

There was no evidence of publication bias for studies on suicides or suicidal ideation, but significant evidence of bias for studies on suicide attempts (Egger’s p = .03). This means that studies with positive findings were more likely to be published than negative studies.

There was, however, strong statistical evidence for differences between studies in the size of their ORs. This indicates that the pooled OR cannot summarize results from all datasets and more work is needed to clarify why the ORs differ among studies.

The authors appropriately caution that their meta-analysis is “not informative on cause-effect relationships,” but offer as a hypothesis that ADHD contributes to suicidal spectrum behaviors (SSBs) through “Impulsivity, a core symptom of ADHD, along with impaired decision-making and risk taking, that characterize a number of individuals with ADHD … Additionally, a sizeable portion of individuals with ADHD present with deficits in executive functions. As executive functions are implicated in the regulation of impulse control and emotions, executive dysfunctions may contribute to SSBs.”

In view of the large to very large effect sizes for suicide and suicidal ideation, the authors advise: “Awareness of this association should prompt practitioners to systematically screen for SSBs in patients with ADHD at the first assessment and at each follow-up, which in turns should contribute to decrease the risk of SSBs. This is particularly noteworthy considering that questionnaires/scales commonly used to screen/assess ADHD symptoms generally do not include suicide related items.”

REFERENCES

Septier M, Stordeur C, Zhang J, Delorme R, Cortese S, Association between suicidal spectrum behaviors and Attention-Deficit/Hyperactivity Disorder: A systematic review and meta-analysis, Neuroscience and Biobehavioral Reviews (2019), https://doi.org/10.1016/j.neubiorev.2019.05.022.

Association Found Between ADHD Risk Genes Involved in Dopamine Signaling and Reduced Estimated Life Expectancy

Stephen V. Faraone, PhD on January 10, 2019

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 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.”

REFERENCES

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.

How to Identify ADHD in Adults with Alcohol Use Disorder (AUD)

Stephen V. Faraone, PhD on December 27, 2018

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.

Is There A Relationship Between ADHD And Migraines?

Stephen V. Faraone, PhD on October 18, 2018

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.

REFERENCES

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

Is There A Relationship Between ADHD And Migraines?

Stephen V. Faraone, PhD on October 18, 2018

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.

REFERENCES
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.

ADHD Is A Risk Factor For Type Two Diabetes And High Blood Pressure, As Well As Other Psychiatric Disorders

Stephen V. Faraone, PhD on October 4, 2018

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.”

REFERENCES

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. https://doi.org/10.1371/journal.pone.0204516.