March 17, 2022

Meta-analysis finds no significant effect of cognitive treatment on ADHD symptoms and executive functioning when randomized controlled trials are blinded

A Chinese study team performed a systematic search of peer-reviewed journal literature to identify randomized controlled trials (RCTs) examining the efficacy of cognitive training as a treatment for youths with ADHD.

Seventeen RCTs with a combined total of 1,075 participants met standards for inclusion in a series of meta-analyses. Seven RCTs used waitlist controls, seven used placebo training, two used treatment-as-usual, and one used active knowledge training. Participants were unmediated in four RCTs, with varying proportions of medicated participants in the remaining thirteen.

A meta-analysis of 15 RCTs, with a combined 789 participants, assessed changes in inattention symptoms following treatment, as rated by parents or clinicians. It found a small-to-medium effect size improvement in symptoms of inattention. There was no indication of publication bias, but between-study heterogeneity was very high.

But that gain vanished altogether when combining only the six RCTs that were blinded, meaning the symptom evaluators had no idea which participants had received cognitive treatment and which participants had not. There was zero difference between the treatment and control groups. Significantly, between-study heterogeneity also diminished markedly, becoming low to moderate.

A second meta-analysis, of 15 RCTs with a combined 723 participants, assessed changes in hyperactivity/impulsivity symptoms following treatment, as rated by parents or clinicians. It found no significant difference between participants who received cognitive training and controls. There was no sign of publication bias, and between-study heterogeneity was moderate-to-high.

The three remaining meta-analyses looked for improvements in executive functions, using the Behavior Rating Inventory of Executive Function (BRIEF).

A meta-analysis of 13 RCTs, with a combined 748 participants, found a small-to-medium effect size improvement in the global executive composite index of BRIEF, as evaluated by parents. There was no sign of publication bias, and between-study heterogeneity was moderate-to-high.

But that improvement again disappeared altogether when considering only the five RCTs that were blinded. Between-study heterogeneity also became insignificant.

A meta-analysis of 6 RCTs with 401 participants found no significant improvement in the behavioral regulation index of BRIEF. Heterogeneity was negligible.

Finally, a meta-analysis of 7 RCTs with 463 participants also found no significant improvement in the metacognition index of BRIEF. In this case, between-study heterogeneity was high.

While acknowledging that "when analyses were set in blinded measures, effect sizes were not statistically significant," the author nevertheless concluded, "In summary, multiple cognitive training alleviates the presentation of inattention and improves general executive function behaviors in children with ADHD." This suggests an underlying bias on the part of the study team in favor of treatment even when not supported by best (i.e., blinded) methodological practices.

Shuxian Chen, Jinglong Yu, QiangZhang, Jin Zhang, Ying Zhang, and Junhong Wang, "Which Factor Is More Relevant to the Effectiveness of the Cognitive Intervention? A Meta-Analysis of Randomized Controlled Trials of Cognitive Training on Symptoms and ExecutiveFunction Behaviors of Children With Attention Deficit Hyperactivity Disorder,". Frontiersin Psychology (2022)published online,https://doi.org/10.3389/fpsyg.2021.810298.

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News Tuesday: Integrating Cognition and Eye Movement

Integrating Cognitive Factors and Eye Movement Data in Reading Predictive Models for Children with Dyslexia and ADHD-I

In a recent study, researchers delved into the complex interplay of cognitive processes and eye movements in children with dyslexia and Attention-Deficit/Hyperactivity Disorder. Their findings shed light on predictive models for reading outcomes in these children compared to typical readers.

The study involved 59 children: 19 typical readers, 21 with ADHD, and 19 with developmental dyslexia (DD), all in the 4th grade and around 9 years old on average. Each group underwent thorough neuropsychological and linguistic assessments to understand their psycholinguistic profiles.

During the study, participants engaged in a silent reading task where the text underwent lexical manipulation. Researchers then analyzed eye movement data alongside cognitive factors like memory, attention, and visual processes.

Using multinomial logistic regression, the researchers evaluated predictive models based on three key measures: a linguistic model focusing on phonological awareness, rapid naming, and reading fluency; a cognitive neuropsychological model incorporating memory, attention, and visual processes; and an additive model combining lexical word properties with eye-tracking data, specifically examining word frequency and length effects.

By integrating eye movement data with cognitive factors, the researchers enhanced their ability to predict the development of dyslexia or ADHD, in comparison to typically developing readers. This approach significantly improved the accuracy of predicting reading outcomes in children with learning disabilities.

These findings have profound implications for understanding and addressing reading challenges in children. By considering both cognitive processes and eye movement patterns, educators and clinicians can develop more effective interventions tailored to the specific needs of children with dyslexia and ADHD.

April 30, 2024

Exploring Gut Microbiota and Diet in Autism and ADHD: What Does the Research Say?


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.

April 9, 2024

Swedish Population Study Confirms Association Between ADHD and Height

Nationwide population study in Sweden confirms association between ADHD and shorter height in children and adolescents, suggests stimulant medications are not a factor

A commonly reported risk associated with ADHD medication is reduced growth in height. But studies to date have generally not adequately described or measured possible confounders, such as genetic factors, prenatal factors, or socioeconomic factors. What if ADHD were associated with reduced height even in the absence of medications? 

An international study team explored this question by performing a nationwide population study comparing data from before (1968-1991) and after (1992-2020) the adoption of stimulant therapy for ADHD in Sweden. 

The country’s single-payer health insurance system that connects patient records with all other national registers through unique personal identification numbers makes such analysis possible. Sweden also has military service conscription, which records the heights of 18-year-old males.

The participants were all 14,268 Swedish males with a diagnosis of ADHD who were drafted into military service at any time from 1968 through 2020. 

Up to five non-ADHD controls were identified for each ADHD case, matched by sex (they had to be male), birth year, and county. The total number of controls was 71,339.

Among 34,586 participants in the period before adoption of stimulant medications (1968-1991), those diagnosed with ADHD had roughly 30% greater odds of being shorter than normal (166-172 vs. 173-185 cm) than typically developing controls. That dropped to 20% greater odds among the 34,714 participants in the cohort following adoption of stimulant medications.

The odds of those diagnosed with ADHD being much shorter than normal (150-165 vs. 173-185 cm) remained identical (about 55% greater) among the almost 30,000 participants in both cohorts.

In other words, there was no increase in the odds of ADHD individuals being shorter than normal after adoption of stimulant therapy in Sweden compared with before such adoption.

Furthermore, after adjusting for known confounders, including birth weight, inflammatory bowel disease, celiac disease, hypothyroidism, anxiety disorders, depression, substance use disorder, and highest parental education, the odds of those diagnosed with ADHD being shorter than normal or much shorter than normal in the 1992-2020 cohort dropped to roughly 10% and 30% greater, respectively.

Could it be the disorder itself rather than stimulant treatment that is associated with reduced height in individuals diagnosed with ADHD?

To address effects of environmental and familial/genetic confounding, the team then compared the entire cohort of males diagnosed with ADHD from 1968 through 2020 with typically developing male relatives, ranging from first cousins to full siblings.

Among full siblings, the odds of those with ADHD diagnoses being shorter (over 90,000 participants) or much shorter (over 77,000 participants) were a statistically significant 14% and 18%, respectively.

The authors concluded, “Our findings suggest that ADHD is associated with shorter height. On a population level, this association was present both before and after ADHD-medications were available in Sweden. The association between ADHD and height was partly explained by prenatal factors, psychiatric comorbidity, low SES [socioeconomic status] and a shared familial liability for ADHD.”

January 9, 2024