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April 9, 2024
In recent years, there has been growing interest in understanding the connection between our gut microbiota (the community of microorganisms in our digestive system) and various neurodevelopmental disorders like autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). A new study by Shunya Kurokawa and colleagues dives deeper into this area, comparing dietary diversity and gut microbial diversity among children with ASD, ADHD, their normally-developing siblings, and unrelated volunteer controls. Let's unpack what they found and what it means.
The Study Setup
The researchers recruited children aged 6-12 years diagnosed with ASD and/or ADHD, along with their non-ASD/ADHD siblings and the unrelated non-ASD/ADHD volunteers. The diagnoses were confirmed using standardized assessments like the Autism Diagnostic Observation Schedule-2 (ADOS-2). The study looked at gut microbial diversity using advanced DNA extraction and sequencing techniques, comparing alpha-diversity indices (which reflect the variety and evenness of microbial species within each gut sample) across different groups. They also assessed dietary diversity through standardized questionnaires.
Key Findings
The study included 98 subjects, comprising children with ASD, ADHD, both ASD and ADHD, their non-ASD/ADHD siblings, and the unrelated controls. Here's what they discovered:
Gut Microbial Diversity: The researchers found significant differences in alpha-diversity indices (like Chao 1 and Shannon index) among the groups. Notably, children with ASD had lower gut microbial diversity compared to unrelated neurotypical controls. This suggests disorder-specific differences in gut microbiota, particularly in children with ASD.
Dietary Diversity: Surprisingly, dietary diversity (assessed using the Shannon index) did not differ significantly among the groups. This finding implies that while gut microbial diversity showed disorder-specific patterns, diet diversity itself might not be the primary factor driving these differences.
What Does This Mean?
The study highlights intriguing connections between gut microbiota and neurodevelopmental disorders like ASD and ADHD. The lower gut microbial diversity observed in children with ASD points towards potential links between gut health and the pathophysiology of ASD. Understanding these connections is crucial for developing targeted therapeutic interventions.
Implications and Future Directions
This research underscores the importance of considering gut microbiota in the context of neurodevelopmental disorders. Moving forward, future studies should account for factors like co-occurrence of ASD and ADHD, as well as carefully control for dietary influences. This will help unravel the complex interplay between gut microbiota, diet, and neurodevelopmental disorders, paving the way for innovative treatments and interventions.
In summary, studies like this shed light on the intricate relationship between our gut health, diet, and brain function. By unraveling these connections, researchers are opening new avenues for understanding and potentially treating conditions like ASD and ADHD.
Kurokawa S, Nomura K, Sanada K, Miyaho K, Ishii C, Fukuda S, Iwamoto C, Naraoka M, Yoneda S, Imafuku M, Matsuzaki J, Saito Y, Mimura M, Kishimoto T. A comparative study on dietary diversity and gut microbial diversity in children with autism spectrum disorder, attention-deficit hyperactivity disorder, their neurotypical siblings, and non-related neurotypical volunteers: a cross-sectional study. J Child Psychol Psychiatry. 2024 Apr 2. doi: 10.1111/jcpp.13962. Epub ahead of print. PMID: 38562118.
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Our research team conducted a study, published in the Journal of the American Academy of Child & Adolescent Psychiatry, to understand how COVID-19 (SARS-CoV-2) affects the mental health of young people. We used a method called Kaplan-Meier survival analysis to figure out how likely kids were to develop new mental health problems, including suicidal thoughts, within two years after being infected. We looked at medical records of 7.5 million children and 5.3 million teenagers who were part of the TriNetX Research Network. Importantly, we focused only on those who didn’t have any mental health issues before.
Of these young people, almost 300,000 children and over 220,000 teens had tested positive for COVID-19. The results were significant: children who had COVID-19 had a 15% chance of being diagnosed with a new mental health condition, compared to just 2.6% for children who didn’t get COVID-19. For teens, the chance was 19% for those infected and 5% for those not infected.
We found that the risk of developing new mental health issues was six times higher in children and four times higher in teens who had COVID-19. This shows that younger kids are more strongly affected.
The study also highlighted that COVID-19 was linked to higher rates of various mental health problems, especially in children. This means it’s really important to screen for mental health issues in young people after they’ve had COVID-19, particularly for those who had severe cases.
Overall, our findings point to the need for special support for kids and teens who may be more vulnerable after the pandemic. It’s clear that the mental health effects of COVID-19 go beyond just physical health, and it’s crucial that doctors and policymakers include mental health care in plans to help young people recover.
Neurodevelopmental conditions often coexist, creating a complex web of challenges for affected individuals. A recent study by Hollingdale et al. delves into the cumulative effects of attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and intellectual disability (ID) on young people’s behavioral and socio-emotional well-being, as well as their overall functioning as rated by clinicians.
The researchers conducted a cross-sectional analysis of 2768 young individuals aged 3-17 years, with a mean age of approximately 11.5 years. Diagnostic information along with caregiver-rated behavioral and socio-emotional data, and clinician-rated functioning scores, were collected from electronic patient records at the point of initial diagnosis.
The study aimed to understand whether the number of neurodevelopmental conditions—ranging from one to three—correlates with more pronounced behavioral and socio-emotional issues, and lower levels of clinician-rated functioning. The behavioral and socio-emotional aspects were assessed using the Strengths and Difficulties Questionnaire, while the Children's Global Assessment Scale was used to evaluate clinician-rated functioning.
The findings revealed that young people with multiple neurodevelopmental conditions tend to exhibit higher levels of inattention and hyperactivity, greater peer-related problems, reduced prosocial behaviors, and poorer overall functioning. Interestingly, this cumulative impact was more evident in males compared to females, with females only showing significant cumulative effects in clinician-rated functioning.
This research underscores the importance of recognizing the compounded difficulties faced by young people with multiple neurodevelopmental conditions. It highlights the need for tailored interventions that address the unique and overlapping challenges presented by ADHD, ASD, and ID. For practitioners, understanding these cumulative effects is crucial for developing effective treatment plans that can better support the holistic development and well-being of these young individuals.
In conclusion, the presence of multiple neurodevelopmental conditions can significantly affect various domains of a young person’s life, with notable differences between males and females. This study provides a critical insight into the intricate nature of these conditions and calls for a more nuanced approach in both research and clinical practice.
Noting that "Growing evidence shows that moderate physical activity (PA) can improve psychological health through enhancement of neurotransmitter systems," and "PA may play a physiological role similar to stimulant medications by increasing dopamine and norepinephrine neurotransmitters, thereby alleviating the symptoms of ADHD," a Chinese team of researchers performed a comprehensive search of the peer-reviewed journal literature for studies exploring the effects of physical activity on ADHD symptoms.
They found nine before-after studies with a total of 232 participants, and fourteen two-group control studies with a total of 303 participants, that met the criteria for meta-analysis.
The meta-analysis of before-after studies found moderate reductions in inattention and moderate-to-strong reductions in hyperactivity/impulsivity. It also reported moderate reductions in emotional problems and small-to-moderate reductions in behavioral problems.
The effect was even stronger among unmediated participants. There was a very strong reduction in inattention and a strong reduction in hyperactivity/impulsivity.
The meta-analysis of two-group control studies found strong reductions in inattention, but no effect on hyperactivity/impulsivity. It also found no significant effect on emotional and behavioral problems.
There was no sign of publication bias in any of the meta-analyses.
The authors concluded, "Our results suggest that PA intervention could improve ADHD-related symptoms, especially inattention symptoms. However, due to a lot of confounders, such as age, gender, ADHD subtypes, the lack of rigorous double-blinded randomized-control studies, and the inconsistency of the PA program, our results still need to be interpreted with caution."
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Background:
Pharmacotherapies, such as methylphenidate, are highly effective for short-term ADHD management, but issues remain with medication tolerability and adherence. Some patients experience unwanted side effects from stimulant medications, leaving them searching for alternative ADHD treatments. Alternative treatments such as cognitive training, behavioral therapies, psychological interventions, neurofeedback, and dietary changes have, so far, shown limited success. Thus, there is a critical need for non-pharmacological options that boost neurocognitive performance and address core ADHD symptoms.
First— What Are NIBS (Non-Invasive Brain Stimulation) Techniques?
Non-invasive brain stimulation (NIBS) techniques, including transcranial direct current stimulation (tDCS), transcranial random noise stimulation (tRNS), transcranial alternating current stimulation (tACS), and repetitive transcranial magnetic stimulation (rTMS) are generating growing attention within the scientific community.
NIBS techniques are methods that use external stimulation, such as magnets or electrical currents, to affect brain activity without any invasive procedures. In transcranial alternating current stimulation (tACS), for example, small electrodes are placed on the scalp of the patient, and a weak electrical current is administered.
The theory behind these techniques is that when a direct current is applied between two or more electrodes placed on specific areas of the head, it makes certain neurons more or less likely to fire. This technique has been successfully used to treat conditions like depression and anxiety, and to aid recovery from stroke or brain injury.
The Study:
Previous meta-analyses have produced conflicting indications of efficacy. A Chinese research team consisting of sports and rehabilitative medicine professionals has just published a network meta-analysis to explore this further, through direct comparison of five critical outcome domains: inhibitory control, working memory, cognitive flexibility, inattention, hyperactivity and impulsivity.
To be included, randomized controlled trials needed to have participants diagnosed with ADHD, use sham control groups, and assess ADHD symptoms and executive functions – such as inhibitory control, working memory, cognitive flexibility, inattention, hyperactivity, and impulsivity – using standardized tests.
A total of thirty-seven studies encompassing 1,615 participants satisfied the inclusion criteria. It is worth noting, however, that the authors did not specify the number of randomized controlled trials nor the number of participants included in each arm of the network meta-analysis.
Furthermore, the team stated, “We checked for potential small study effects and publication bias by conducting comparison-adjusted funnel plots,” but did not share their findings. They also did not provide information on outcome variation (heterogeneity) among the RCTs.
Results:
Ultimately, none of the interventions produced significant improvements in ADHD symptoms, whether in inattention symptoms or hyperactivity/impulsivity symptoms. Likewise, none of the interventions produced significant improvements in inhibitory control. Some tDCS interventions enhanced working memory and cognitive flexibility, but details about trial numbers and participants were missing. The team concluded, “none of the NIBS interventions significantly improved inhibitory control compared to sham controls. … In terms of working memory, anodal tDCS over the left DLPFC plus cathodal tDCS over the right DLPFC … and anodal tDCS over the right inferior frontal cortex (rIFC) plus cathodal tDCS over the right supraorbital area ... were associated with significant improvements compared to sham stimulation. For cognitive flexibility, only anodal tDCS over the left DLPFC plus cathodal tDCS over the right supraorbital area demonstrated a statistically significant benefit relative to sham. ... Compared to the sham controls, none of the NIBS interventions significantly improved inattention. ... Compared to the sham controls, none of the NIBS interventions significantly improved hyperactivity and impulsivity.”
How Should We Interpret These Results?
In a word, skeptically.
If one were to read just the study’s abstract, which states, “The dual-tDCS and a-tDCS may be considered among the preferred NIBS interventions for improving cognitive function in ADHD”, it might seem that the takeaway from this study is that this combination of brain stimulation techniques might be a viable treatment option for those with ADHD. Upon closer inspection, however, the results do not suggest that any of these methods significantly improve ADHD symptoms. Additionally, this study suffers from quite a few methodological flaws, so any results should be viewed critically.
Background:
Despite recommendations for combined pharmacological and behavioral treatment in childhood ADHD, caregivers may avoid these options due to concerns about side effects or the stigma that still surrounds stimulant medications. Alternatives like psychosocial interventions and environmental changes are limited by questionable effectiveness for many patients. Increasingly, patients and caregivers are seeking other therapies, such as neuromodulation – particularly transcranial direct current stimulation (tDCS).
tDCS seeks to enhance neurocognitive function by modulating cognitive control circuits with low-intensity scalp currents. There is also evidence that tDCS can induce neuroplasticity. However, results for ADHD symptom improvement in children and adolescents are inconsistent.
The Method:
To examine the evidence more rigorously, a Taiwanese research team conducted a systematic search focusing exclusively on randomized controlled trials (RCTs) that tested tDCS in children and adolescents diagnosed with ADHD. They included only studies that used sham-tDCS as a control condition – an essential design feature that prevents participants from knowing whether they received the active treatment, thereby controlling for placebo effects.
The Results:
Meta-analysis of five studies combining 141 participants found no improvement in ADHD symptoms for tDCS over sham-TDCS. That held true for both the right and left prefrontal cortex. There was no sign of publication bias, nor of variation (heterogeneity) in outcomes among the RCTs.
Meta-analysis of six studies totaling 171 participants likewise found no improvement in inattention symptoms, hyperactivity symptoms, or impulsivity symptoms for tDCS over sham-TDCS. Again, this held true for both the right and left prefrontal cortex, and there was no sign of either publication bias or heterogeneity.
Most of the RCTs also performed follow-ups roughly a month after treatment, on the theory that induced neuroplasticity could lead to later improvements.
Meta-analysis of four RCTs combining 118 participants found no significant improvement in ADHD symptoms for tDCS over sham-TDCS at follow-up. This held true for both the right and left prefrontal cortex, with no sign of either publication bias or heterogeneity.
Meta-analysis of five studies totaling 148 participants likewise found no improvement in inattention symptoms or hyperactivity symptoms for tDCS over sham-TDCS at follow-up. AS before, this was true for both the right and left prefrontal cortex, with no sign of either publication bias or heterogeneity.
The only positive results came from meta-analysis of the same five studies, which reported a medium effect size improvement in impulsivity symptoms at follow-up. Closer examination showed no improvement from stimulation of the right prefrontal cortex, but a large effect size improvement from stimulation of the left prefrontal cortex.
Interpretation:
It is important to note that the one positive result was from three RCTs combining only 90 children and adolescents, a small sample size. Moreover, when only one of sixteen combinations yields a positive outcome, that begins to look like p-hacking for a positive result.
In research, scientists use something called a “p-value” to determine if their findings are real or just due to chance. A p-value below 0.05 (or 5%) is considered “statistically significant,” meaning there's less than a 5% chance the result happened by pure luck.
When testing twenty outcomes by this standard, one would expect one to test positive by chance even if there is no underlying association. In this case, one in 16 comes awfully close to that.
To be sure, the research team straightforwardly reported all sixteen outcomes, but offered an arguably over-positive spin in their conclusion: “Our study only showed tDCS-associated impulsivity improvement in children/adolescents with ADHD during follow-ups and anode placement on the left PFC. ... our findings based on a limited number of available trials warrant further verification from large-scale clinical investigations.”
Children and adolescents with ADHD tend to be less active and more sedentary than their typically developing peers. This is concerning, since physical activity benefits mental, physical, and social development. For youth with ADHD, being active can improve symptoms like inattention, working memory, and inhibitory control.
A major barrier to physical activity for children and adolescents with ADHD is limited motor competence. This stems from challenges in developing basic motor skills and more complex abilities needed for sports and advanced movements.
Difficulties in developing fundamental movement skills – such as locomotor (running, jumping), object-control (throwing, catching), and stability skills (balancing, turning) – can reduce motor competence and limit physical activity. These basic movements are learned and refined with practice and age, not innate abilities.
To date, research on the link between ADHD and motor competence has remained inconclusive. This systematic review and meta-analysis by a Spanish research team therefore aimed to determine whether children and adolescents with ADHD differ in motor competence from those with typical development (TD).
Studies had to include children and adolescents diagnosed with ADHD. They had to involve a full motor assessment battery, not just one test, and present motor competence data for both ADHD and TD groups.
The team excluded studies involving participants with other neurodevelopmental disorders or cognitive impairments, unless separate data for the ADHD subgroup were reported.
Meta-analysis of six studies combining 323 children and adolescents found that typically developing individuals were twelve times more likely to score in the 5th percentile of the Movement Assessment Battery for Children as their peers diagnosed with ADHD. They were also three times more likely to score in the 15th percentile (five studies, 289 participants). Results were consistent across the studies (low heterogeneity). All included studies were randomized.
Meta-analysis of five studies totaling 198 participants using the Test of Gross Motor Development reported significant deficits in both locomotor skills and object control skills among children and adolescents diagnosed with ADHD relative to their typically developing peers. In this case, however, results were inconsistent across studies (very high heterogeneity), and one of the studies was unrandomized. Because the team published only unstandardized mean differences, there was no indication of effect sizes.
Meta-analysis of two studies encompassing 164 participants using the Bruininks-Oseretsky Test of Motor Proficiency similarly yielded significant deficits among children and adolescents diagnosed with ADHD relative to their typically developing peers, but in this case with low heterogeneity. Notably, one of the two studies was not randomized.
Moreover, the team made no assessment of publication bias.
The team concluded, “The findings of this review indicate that children and adolescents with ADHD show significantly lower levels of motor competence compared to their TD peers. This trend was evident across a range of validated assessment tools, including the MABC, BOT, TGMD, and other standardized test batteries. Future research should aim to reduce methodological heterogeneity and further investigate the influence of factors such as ADHD subtypes and comorbid conditions on motor development trajectories.”
However, without a publication bias assessment, reliance on unrandomized studies in two of the tests, no indication of effect size in the same two tests, and small sample sizes, these results are at best suggestive, and will require further research to confirm.
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