September 8, 2021

How do psychiatric comorbidities affect risk of premature death among children and adults with ADHD?


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 27 years 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 disorders increased risk by roughly two and a half times.

The co-variate analysis helped tease out what portion of the risk was associated with ADHD alone versus comorbid conditions. Adjusting for the 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 the 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.

Shihua Sun, MD; Ralf Kuja-Halkola, Ph.D.; Stephen V. Faraone,  Ph.D.; Brian M. D'Onofrio, Ph.D.; Søren Dalsgaard, Ph.D.; Zheng Chang, Ph.D.; Henrik Larsson, Ph.D., "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.2019.1944Published online August 7, 2019.

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Swedish Nationwide Population Study Finds Strong Association Between ADHD and Sleep Disorder Diagnoses and Sleep Medication Prescriptions

There has been consistent evidence of an association between ADHD and subjectively reported sleep problems even in patients not medicated for the disorder. There have also been studies using wrist-worn actigraphy (a wrist watch-like device that measures gross motor activity) and sleep lab-based polysomnography that measure objective sleep parameters. 

What has been missing are large population-based cohort studies to explore the prevalence rates of different sleep disorders and medical prescriptions in ADHD. 

Methods Used: 

Sweden has a single-payer health insurance system and a series of national population registers that track virtually its entire population. Using the Swedish Total Population Register, a local research team created a cohort of all 6,470,658 persons born between 1945 and 2008. They linked this to the Swedish National Patient Register, which includes inpatient hospitalizations from 1975 to 2013, and outpatient specialist diagnoses from 2001 to 2013, to identify diagnoses of sleep disorders. They also linked to the Prescribed Drug Register, covering 2005 to 2013, to identify prescriptions for sleep medications. 

Summary of Findings: 

Overall, persons with ADHD were eight times more likely to be diagnosed with any sleep disorder relative to normally developing peers. Broken down by age, adolescents with ADHD were 16 times more likely to receive such diagnoses, young adults (18-30) twelve times more likely, children and mid-age adults (31-45) eight times more likely, and older adults six times more likely. 

Broken down by specific sleep disorder diagnoses, relative to normally developing peers, persons with ADHD were: 

  • Five times more likely to have sleep terrors and seven times more likely to have nightmares. 
  • Six times more likely to sleepwalk. 
  • Seven times more likely to have restless leg syndrome. 
  • Sixteen times more likely to have insomnia. 
  • Nineteen times more likely to have disorders of sleep/wake schedule (circadian rhythms). 
  • Twenty times more likely to have hypersomnia (excessive sleeping). 
  • Over seventy times more likely to exhibit narcolepsy (daytime sleepiness) and cataplexy (sudden loss of muscle tone leading to collapse). 

As for sleep medication, relative to normally developing peers, persons with ADHD were: 

  • Seven times more likely to be prescribed the hypnotic zolpidem (Ambien). 
  • Eight times more likely to be prescribed the hypnotic zopiclone or the antihistamine propriomazine. 
  • Ten times more likely to be prescribed the sedative and hypnotic zaleplon (Sonata). 
  • Fourteen times more likely to be prescribed any sleep medication. 
  • 37 times more likely to be prescribed melatonin, the body’s natural sleep-inducing hormone, which is a prescription medication in Europe. 

Conclusion: 

The team concluded, “Our findings also suggest that greater clinical attention should be directed towards addressing sleep problems in individuals with ADHD. This entails implementing proactive measures through sleep education programmes and providing both pharmacological and non-pharmacological approaches such as cognitive behavioural therapy and parental sleep training.” 

December 12, 2024

Effect of Physical Activity on Attention in School-age Children with ADHD: Systematic Review and Meta-Analysis

Overview

Attention is a critical determinant of academic achievement, influencing domains such as language, literacy, and mathematics. To explore whether physical activity can improve attention in children with ADHD, an international team conducted a meta-analysis of peer-reviewed studies. The goal was to evaluate the impact of various physical activity regimens on attention-related outcomes in this population.

Methods

The researchers performed a comprehensive search of the medical literature to identify studies examining the effects of physical activity on attention in schoolchildren with ADHD. They included 10 studies with a total of 474 participants in their meta-analysis. The studies evaluated two main types of physical activity:

  • Mentally engaging physical activities
  • Aerobic exercise

Additionally, they examined variations based on the frequency, duration, and type of control groups used in the studies. To assess consistency, they also analyzed heterogeneity (variability of outcomes) and checked for potential publication bias.

Summary

Key findings from the meta-analysis include:

  1. Effectiveness of Mentally Engaging Activities:some text
    • Seven studies (168 participants) involving mentally engaging physical activities showed large reductions in attention problems.
    • Heterogeneity was significantly reduced for these studies.
  2. Effectiveness of Aerobic Exercise:some text
    • Three studies (306 participants) using aerobic exercise alone found no improvements in attention.
  3. Impact of Control Groups:some text
    • Studies with no intervention as a control group (4 studies, 81 participants) reported large improvements in attention problems.
    • Those comparing physical activity with other interventions (6 studies, 393 participants) found only small improvements.
  4. Frequency and Duration:some text
    • Duration of physical activity made little difference. Studies with sessions of an hour or more had slightly better outcomes, but the difference was not significant.
    • Surprisingly, lower frequency was more effective:some text
      • One to two sessions per week (7 studies, 162 participants) led to large reductions in attention problems.
      • Three or more sessions per week (3 studies, 312 participants) showed no improvement.
Conclusion

The authors concluded that mentally engaging exercise is more effective than aerobic exercise in improving attention problems in schoolchildren with ADHD. Furthermore, higher frequency and longer duration of physical activity do not necessarily yield better outcomes.

This research underscores the importance of tailoring physical activity interventions to emphasize cognitive engagement over intensity or duration. By refining strategies, educators and parents can better support children with ADHD in achieving academic success.   But take note:  given the results from controlled studies, it seems clear that if there is a positive effect of exercise, it is very small so should not replace standard treatments for ADHD.  

NEWS TUESDAY: How Stimulant Use in Childhood ADHD May Impact Brain Connectivity and Symptom Improvement

Previous studies have examined how stimulant medications affect the brain in controlled settings, but less is known about their impact in real-world conditions, where children may not always take their medication consistently or may combine it with other treatments. A new study leverages data from the Adolescent Brain Cognitive Development (ABCD) study to explore how real-world stimulant use impacts brain connectivity and ADHD symptoms over two years.

Changes in Brain Connectivity Researchers used brain imaging data from the ABCD study to examine the functional connectivity—communication between brain areas—of six regions within the striatum, a brain area involved in motivation and movement control. They focused on how stimulant use influenced connectivity between the striatum and other networks involved in executive functioning and visual-motor control.

The study found that stimulant exposure was linked to reduced connectivity between key striatal areas (such as the caudate and putamen) and large brain networks, including the frontoparietal and visual networks. These changes were more pronounced in children taking stimulants compared to those who were not medicated, as well as compared to typically developing children. Importantly, this reduction in connectivity seemed to regulate certain brain networks that are typically altered in children with ADHD.

Symptom Improvement In addition to brain changes, 14% of children taking stimulants experienced a significant reduction in ADHD symptoms over the two-year period. These children showed the strongest connectivity reductions between the right putamen and the visual network, suggesting that stimulant-induced connectivity changes may contribute to improvements in visual attentional control, which is a common challenge for children with ADHD.

Why This Matters This study is one of the first to examine how stimulant use in real-world conditions affects brain networks in children with ADHD over time. The findings suggest that stimulants may help normalize certain connectivity patterns associated with ADHD, particularly in networks related to attention and control. These insights could help clinicians better understand the potential long-term effects of stimulant treatment and guide personalized approaches to ADHD management.

Conclusion Stimulant medications appear to alter striatal-cortical connectivity in children with ADHD, with some changes linked to symptom improvement. This research highlights the potential for stimulant medications to impact brain networks in ways that support attention and control, highlighting the importance of understanding how real-world medication use influences ADHD treatment outcomes.

December 3, 2024