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February 4, 2021
The ENIGMA-ADHD Working Group published their second large study on the brains of people with ADHD in the American Journal of Psychiatry this month. In this second study, the focus was on the cerebral cortex, which is the outer layer of the brain.
ADHD symptoms include inattention and/or hyperactivity and acting impulsively. The disorder affects more than one in 20 (5.3%) children, and two-thirds of those diagnosed continue to experience symptoms as adults.
In this study, researchers found subtle differences in the brain’s outer layer - the cortex - when they combined brain imaging data on almost 4,000 participants from 37 research groups worldwide. The differences were only significant for children and did not hold for adolescents or adults. The childhood effects were most prominent and widespread for the surface area of the cortex. More focal changes were found in the thickness of the cortex. All differences were subtle and detected only at a group level, and thus these brain images cannot be used to diagnose ADHD or guide its treatment.
These subtle differences in the brain’s cortex were not limited to people with the clinical diagnosis of ADHD: they were also present - in a less marked form - in youth with some ADHD symptoms. This second finding results from a collaboration between the ENIGMA-ADHD Working Group and the Generation-R study from Rotterdam, which has brain images on 2700 children aged 9-11 years from the general population. The researchers found more symptoms of inattention to be associated with a decrease in cortical surface area. Furthermore, siblings of those with ADHD showed changes to their cortical surface area that resembled their affected sibling. This suggests that familial factors such as genetics or shared environment may play a role in brain cortical characteristics.
This is the largest study to date to look at the cortex of people with ADHD. It included 2246 people with a diagnosis of ADHD and 1713 people without, aged between four and 63 years old. This is the second study published by the ENIGMA-ADHD Working Group; the first examined structures that are deep in the brain. The ADHD Working Group is one of over 50 working groups of the ENIGMA Consortium, in which international researchers pull together to understand the brain alterations associated with different disorders and the role of genetic and environmental factors in those alterations.
The authors say the findings could help improve understanding of the disorder. ‘We identify cortical differences that are consistently associated with ADHD by combining data from many different research groups internationally. We find that the differences extend beyond narrowly-defined clinical diagnoses and are seen, in a less marked manner, in those with some ADHD symptoms and in unaffected siblings of people with ADHD. This finding supports the idea that the symptoms underlying ADHD may be a continuous trait in the population, which has already been reported by other behavioral and genetic studies.’. In the future, the ADHD Working Group hopes to look at additional key features in the brain- such as the structural connections between brain areas – and to increase the representation of adults affected by ADHD, in whom limited research has been performed to date.
See: https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2019.18091033
EBI-ADHD:
If you live with ADHD, treat ADHD, or write about ADHD, you’ve probably run into the same problem: there’s a ton of research on treatments, but it’s scattered across hundreds of papers that don’t talk to each other. The EBI-ADHD website fixes that.
EBI-ADHD (Evidence-Based Interventions for ADHD) is a free, interactive platform that pulls together the best available research on how ADHD treatments work and how safe they are. It’s built for clinicians, people with ADHD and their families, and guideline developers who need clear, comparable information rather than a pile of PDFs. EBI-ADHD Database The site is powered by 200+ meta-analyses covering 50,000+ participants and more than 30 different interventions. These include medications, psychological therapies, brain-stimulation approaches, and lifestyle or “complementary” options.
The heart of the site is an interactive dashboard. You can:
The dashboard then shows an evidence matrix: a table where each cell is a specific treatment–outcome–time-point combination. Each cell tells you two things at a glance:
Clicking a cell opens more detail: effect sizes, the underlying meta-analysis, and how the certainty rating was decided.
EBI-ADHD is not just a curated list of papers. It’s built on a formal umbrella review of ADHD interventions, published in The BMJ in 2025. That review re-analyzed 221 meta-analyses using a standardized statistical pipeline and rating system.
The platform was co-created with 100+ clinicians and 100+ people with lived ADHD experience from around 30 countries and follows the broader U-REACH framework for turning complex evidence into accessible digital tools.
Why it Matters
ADHD is one of the most studied conditions in mental health, yet decisions in everyday practice are still often driven by habit, marketing, or selective reading of the literature. EBI-ADHD offers something different: a transparent, continuously updated map of what we actually know about ADHD treatments and how sure we are about it.
In short, it’s a tool to move conversations about ADHD care from “I heard this works” to “Here’s what the best current evidence shows, and let’s decide together what matters most for you.”
The Background:
Meta-analyses have previously suggested a link between maternal thyroid dysfunction and neurodevelopmental disorders (NDDs) in children, though some studies report no significant difference. Overweight and obesity are more common in children and adolescents with NDDs. Hypothyroidism is often associated with obesity, which may result from reduced energy expenditure or disrupted hormone signaling affecting growth and appetite. These hormone-related parameters could potentially serve as biomarkers for NDDs; however, research findings on these indicators vary.
The Study:
A Chinese research group recently released a meta-analysis examining the relationship between neurodevelopmental disorders (NDDs) and hormone levels – including thyroid, growth, and appetite hormones – in children and adolescents.
The analysis included peer-reviewed studies that compared hormone levels – such as thyroid hormones (FT3, FT4, TT3, TT4, TSH, TPO-Ab, or TG-Ab), growth hormones (IGF-1 or IGFBP-3), and appetite-related hormones (leptin, ghrelin, or adiponectin) – in children and adolescents with NDDs like ADHD, against matched healthy controls. To be included, NDD cases had to be first-diagnosis and medication-free, or have stopped medication before testing. Hormone measurements needed to come from blood, urine, or cerebrospinal fluid samples, and all studies were required to provide both means and standard deviations for these measurements.
Meta-analysis of nine studies encompassing over 5,700 participants reported a medium effect size increase in free triiodothyronine (FT3) in children and adolescents with ADHD relative to healthy controls. There was no indication of publication bias, but variation between individual study outcomes (heterogeneity) was very high. Further analysis showed FT3 was only significantly elevated in the predominantly inattentive form of ADHD (three studies), again with medium effect size, but not in the hyperactive/impulsive and combined forms.
Meta-analysis of two studies combining more than 4,800 participants found a small effect size increase in thyroid peroxidase antibody (TPO-Ab) in children and adolescents with ADHD relative to healthy controls. In this case, the two studies had consistent results. Because only two studies were involved, there was no way to evaluate publication bias.
The remaining thyroid hormone meta-analyses, involving 6 to 18 studies and over 5,000 participants in each instance, found no significant differences in levels between children and adolescents with ADHD and healthy controls.
Meta-analyses of six studies with 317 participants and two studies with 192 participants found no significant differences in growth hormone levels between children and adolescents with ADHD and healthy controls.
Finally, meta-analyses of nine studies with 333 participants, five studies with 311 participants, and three studies with 143 participants found no significant differences in appetite-related hormone levels between children and adolescents with ADHD and healthy controls.
The Conclusion:
The team concluded that FT3 and TPO-Ab might be useful biomarkers for predicting ADHD in youth. However, since FT3 was only linked to inattentive ADHD, and TPO-Ab’s evidence came from just two studies with small effects, this conclusion may overstate the meta-analysis results.
Our Take-Away:
Overall, this meta-analysis found only limited evidence that hormone differences are linked to ADHD. One thyroid hormone (FT3) was higher in children with ADHD—mainly in the inattentive presentation—but the findings varied widely across studies. Another marker, TPO-Ab, showed a small increase, but this came from only two studies, making the result less certain. For all other thyroid, growth, and appetite-related hormones, the researchers found no meaningful differences between children with ADHD and those without. While FT3 and TPO-Ab may be worth exploring in future research, the current evidence is not strong enough to consider them reliable biomarkers.
Background:
Recent progress in reproductive medicine has increased the number of children conceived via assisted reproductive techniques (ART). These include:
Although ART helps with infertility, there are concerns about its long-term effects on offspring, especially regarding neurodevelopment. Factors such as hormonal treatments, gamete manipulation, altered embryonic environments, as well as parental age and infertility, may influence brain development and raise the risk of neurodevelopmental and mental health disorders.
With previous studies finding conflicting results on a possible association between ART and increased risk of mental health disorders, an Indian research team has just published a new meta-analysis exploring this topic.
The Study:
Studies were eligible if they were observational (cohort, case-control, or cross-sectional), reported confounder-adjusted effect sizes for ADHD, and were published in English in peer-reviewed journals.
A meta-analysis of eight studies encompassing nearly twelve million individuals indicated a 7% higher prevalence of ADHD in offspring conceived via IVF/ICSI compared to those conceived naturally. The heterogeneity among studies was minimal, and no evidence of publication bias was observed.
The study’s 95% confidence interval ranged from 4% to 10%. Further analysis of five studies comprising almost nine million participants that distinguished outcomes by sex revealed that the increase in ADHD risk among female offspring was not statistically significant. In contrast, the elevated risk in male offspring persisted, though it was marginally significant, with the lower bound of the confidence limit at only 1%.
Results:
A meta-analysis of three studies (1.4 million participants) found a 13% higher rate of ADHD in children conceived via ovulation induction/intrauterine insemination (OI/IUI) compared to natural conception. The effect size, though doubled, remains small. Minimal heterogeneity and no publication bias were observed.
The team concluded, “The review found a small but statistically significant moderate certainty evidence of an increased risk of ADHD in those conceived through ART, compared to spontaneous conception. The magnitude of observed risk is small and is reassuring for parents and clinicians.”
Our Take-Away:
Overall, the meta-analysis points to a small, but measurable increase in ADHD diagnoses among children conceived through ART, but the effect sizes are modest and supported by moderate-certainty evidence. And we must always keep in mind that the researchers who wrote the original articles could not correct for all possible confounds. These findings suggest that while reproductive technologies may introduce slight variation in neurodevelopmental outcomes, the effects are small and uncertain. For families and clinicians, the results are generally reassuring: ART remains a safe and effective avenue to parenthood, and the results of this study should not be viewed as a prohibitive concern. Thoughtful developmental monitoring and open, evidence-based counseling can help ensure that ART-conceived children receive support that caters to their individual needs.
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