August 19, 2021

Association found between ADHD risk genes involved in dopamine signaling and reduced estimated life expectancy

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 in1987-1988 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, for 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 of on expected longevity. Participants also provided blood samples that enabled gene typing.

For the DAT1 gene, participants who had the homozygous-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 in estimated life expectancy.

In a related study, several background traits were found to be significantly predictive of variance 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 10/10pairings, 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 public policy.

"With these limitations in mind, they concluded, the present study demonstrated that two ADHD risk genes (DB Hand 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/aiming.b.32711.

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Network Meta-analysis Explores Long-term Efficacy of Nonpharmacological Treatments for Improving Inhibitory Control in Children and Adolescents with ADHD

Background Info:

Executive functions include inhibitory control, working memory, and cognitive flexibility. Inhibitory control is the ability to suppress distractions and focus on goals, which is the main deficit in ADHD. 

Children and adolescents with ADHD often have off-task, unrelated thoughts and are easily distracted, limiting their sustained attention. This makes it difficult for them to focus on tasks and leads to impulsive behaviors that affect their daily life, academics, and social interactions. Improving inhibitory control in ADHD children and adolescents is essential. 

Stimulant medications are commonly used to treat ADHD. However, side effects like insomnia, loss of appetite, and headaches may make parents hesitant to use these medications for their children. 

Non-pharmacological treatments like cognitive training, behavior therapy, and physical exercise have gained attention for their lack of side effects. Research shows that some non-pharmacological methods can improve cognitive outcomes significantly, underscoring their potential in treating ADHD. 

Study:

A Chinese research team identified four key gaps in current research on non-pharmacological treatments for inhibitory control in children with ADHD: 

  • Existing meta-analyses seldom differentiate between short-term and long-term interventions.  
  • Most studies focus primarily on short-term effects and neglect evaluation of maintenance effects through follow-up assessments.  
  • New treatment methods, such as meditation and board games, have not been systematically assessed in meta-analyses for their impact on inhibitory control in children and adolescents with ADHD, leaving their effectiveness uncertain.  
  • Traditional meta-analysis does not tell us which intervention is most effective. Without this comparative analysis, it is difficult to rank efficacy. 

The team therefore performed a network meta-analysis of long-term randomized controlled trials (RCTs) to assess and rank the effectiveness of various non-pharmacological treatments on inhibitory control in children and adolescents with ADHD. 

The team included only RCTs relying on professional diagnoses of ADHD, excluding those based only on parent and teacher rating scales.  

The included studies measured inhibitory control using objective neurocognitive tasks, such as the Stroop test and the Go/No-Go test, to reduce potential subjective bias. Studies relying on parent- or teacher-reported questionnaires were excluded. 

Controls either received no intervention or placebo, such as watching running videos and attending history classes. 

Meta-analysis of 16 studies combining 546 participants found large short-term effect size improvements in inhibitory control from physical exercise. But the two studies with a total of 110 participants that performed a follow-up test reported only a small-to-medium effect size improvement. 

For cognitive training, a meta-analysis of fifteen studies totaling 674 participants reported a medium effect size of short-term improvement in inhibitory control. The ten studies with 563 participants that performed a follow-up test found only a small effect size improvement since treatment initiation. 

For behavioral therapy, meta-analysis of six studies encompassing 244 individuals likewise found a medium effect size short-term improvement in inhibitory control. In this case, however two studies combining 91 participants that performed a follow-up test reported that the medium effect size improvement was maintained. 

For neurofeedback, meta-analysis of seven studies encompassing 186 individuals found a small-to-medium effect size short-term improvement in inhibitory control. The only study that performed a follow-up test reported a small effect size improvement since treatment initiation. 

The two studies with a combined 44 individuals exploring board games found no significant improvement in inhibitory control. Likewise, the two studies combining 32 participants that explored meditation found no significant improvement in inhibitory control. 

There was no indication of publication bias. 

Conclusion:

The team concluded, “Existing evidence shows that physical exercise, behavior therapy, cognitive training, and neurofeedback can effectively improve the inhibitory control of children and adolescents with ADHD. However, meditation, EMG feedback, and board games did not significantly affect inhibitory control. Physical exercise has the best effect among all non-pharmacological treatments, but its impact will be weakened after intervention. Behavior therapy and cognitive training had a slightly lower effect, but they have a better maintenance effect.” 

Ultimately, the study results suggest that non-drug treatments can help children and teens with ADHD improve their ability to control their actions and stay focused. Some methods, like physical exercise, work well at first but may fade once the activity stops. Other methods, like behavioral therapy and cognitive training, may take a little longer to show results but can last longer and make a bigger difference over time. Ultimately, and most importantly, because this work did not study the symptoms of ADHD or its real-world impairments, it provides no reason to change current treatment practices for ADHD.

July 16, 2025

The Role of Serotonin in ADHD and Its Many Comorbidities

Serotonin is a key chemical in the body that helps regulate mood, behavior, and also many physical functions such as sleep and digestion. It has also been linked to how ADHD (attention-deficit/hyperactivity disorder) develops in the brain. This study looks at how serotonin may be involved in both the mental health and physical health conditions that often occur alongside ADHD.

It is well-established that ADHD is more than just trouble focusing or staying still. For many, it brings along a host of other physical and mental health challenges. It is very common for those with ADHD to also have other diagnosed disorders. For example, those with ADHD are often also diagnosed with depression, anxiety, or sleep disorders. When these issues overlap, they are called comorbidities. 

A new comprehensive review, led by Dr. Stephen V. Faraone and colleagues, delves into how serotonin (5-HT), a major brain chemical, may be at the heart of many of these common comorbidities.

Wait! I thought ADHD had to do with Dopamine–Why are we looking at Serotonin?

Serotonin is a neurotransmitter most often linked to mood, but its role in regulating the body has much broader implications. It regulates sleep, digestion, metabolism, hormonal balance, and even immune responses. Although ADHD has long been associated with dopamine and norepinephrine dysregulation, this review suggests that serotonin also plays a central role, especially when it comes to comorbid conditions.

The Study:

  • Objective: To systematically review which conditions commonly co-occur with ADHD and determine whether serotonin dysfunction might be a common thread linking them.

  • Method: The authors combed through existing literature up to March 2024, analyzing evidence for serotonin involvement in each comorbidity associated with ADHD.

  • Scope: 182 psychiatric and somatic conditions were found to frequently occur in people with ADHD.

Key Findings

  • 74% of Comorbidities Linked to Serotonin: Of the 182 comorbidities identified, 135 showed evidence of serotonergic involvement—91 psychiatric and 44 somatic (physical) conditions.

  • Psychiatric Comorbidities: These include anxiety disorders, depression, bipolar disorder, and obsessive-compulsive disorder—all of which have long-standing associations with serotoninergic dysfunction.

  • Somatic Comorbidities: Conditions like irritable bowel syndrome (IBS), migraines, and certain sleep disorders also showed a significant serotonergic link.

This research suggests that serotonin dysregulation could explain the diverse and sometimes puzzling range of symptoms seen in ADHD patients. It supports a more integrative model of ADHD—one that goes beyond the brain’s attention, reward and executive control circuits and considers broader physiological and psychological health.

future research into the role of serotonin could help develop more tailored interventions, especially for patients who don't respond well to stimulant medications. Future studies may focus on serotonin’s role in early ADHD development and how it interacts with environmental and genetic factors.

The Take-Away: 

This study is a strong reminder that ADHD is a complex, multifaceted condition. Differential diagnosis is crucial to properly diagnosing and treating ADHD. Clinicians' understanding of the underlying link between ADHD and its common comorbidities may help future ADHD patients receive the individualized care they need. By shedding light on serotonin’s wide-reaching influence, this study may provide a valuable roadmap for improving how we diagnose and treat those with complex comorbidities in the future. 

July 14, 2025

Undiagnosed ADHD May Be Undermining Diabetes Control in Adults with Type 1 Diabetes

Our recent study, published in the Journal of Clinical Medicine, aims to shed light on an under-recognized challenge faced by many adults with Type 1 diabetes (T1D): attention-deficit/hyperactivity disorder (ADHD) symptoms.

We surveyed over 2,000 adults with T1D using the Adult Self-Report Scale (ASRS) for ADHD and analyzed their medical records. Of those who responded, nearly one-third met the criteria for ADHD symptoms—far higher than the general population average. Notably, only about 15% had a formal diagnosis or were receiving treatment.

The findings are striking: individuals with higher ADHD symptom scores had significantly worse blood sugar control, as indicated by higher HbA1c levels. Those flagged as "ASRS positive" were more than twice as likely to have poor glycemic control (HbA1c ≥ 8.0%). They also reported higher levels of depressive symptoms.

As expected, ADHD symptoms decreased with age but remained more common than in the general public. No strong links were found between ADHD symptoms and other cardiometabolic issues.

This study highlights a previously overlooked yet highly significant factor in diabetes management. ADHD-related difficulties—such as forgetfulness, inattention, or impulsivity—can make managing a complex condition like T1D more difficult. The researchers call for more screening and awareness of ADHD in adults with diabetes, which could lead to better mental health and improved blood sugar outcomes.

Takeaway: If you or a loved one with T1D struggles with focus, organization, or consistent self-care, it may be worth exploring whether ADHD could be part of the picture. Early identification and support are crucial to managing this common comorbidity. 

July 10, 2025