March 21, 2022

Meta-analysis finds consistent time perception impairments in persons with ADHD

An international study team conducted the first meta-analysis of studies examining differences in time perception between persons with ADHD and normally developing controls. A systematic search of the peer-reviewed medical literature identified 55 studies that could be combined into various subgroups for meta-analysis.

A meta-analysis of 25 studies with a combined 1,633 participants looking at time discrimination found a medium effect size deficit among persons with ADHD in the number of correct comparisons between the length of two signals. There was little between-study heterogeneity and no sign of publication bias.

Turning to time estimation, a meta-analysis of eight studies with a combined 1,024 participants found a small-to-medium effect size increase in absolute errors (i.e., the absolute value of deviation between the specified and the estimated time interval, representing the absolute amount of error regardless of its direction) among persons with ADHD, compared to controls. Again, there was little between-study heterogeneity and no sign of publication bias.

A meta-analysis of seven studies with combined 380 participants looked at differences in time production, in which they had to produce a previously specified time interval by pressing and holding a button. In this case, those with ADHD manifested a small effect size increase in absolute error relative to their normally developing counterparts. There was moderate between-study heterogeneity and no sign of publication bias.

Finally, a meta-analysis of 26 studies with combined 2,364 participants examined differences in time reproduction, in which they had to reproduce the duration of a previously presented stimulus by pressing and holding a button. Here, those with ADHD exhibited a medium effect size increase in absolute error. There was moderate between-study heterogeneity and no indication of publication bias.

An acknowledged limitation of these meta-analyses was the inability to assess the effects of pharmacological treatment. In addition, 84% of the studies did not report the ethnicity of participants.

The team concluded, "We found meta-analytic evidence of significant deficits in individuals with ADHD across all timing paradigms ... individuals with ADHD have difficulties to discriminate stimuli that vary from each other for only several milliseconds, and they are more variable in their time estimates of several seconds irrespective of the paradigm examined, which may both be driven by their lowered alertness levels."

They suggested that this might eventually become a criterion to help diagnose ADHD: "Our findings have possible clinical implications, albeit not currently directly applicable to the clinical practice. As timing has been proposed as an independent neuropsychological pathway to ADHD, timing tasks should be considered in the clinical assessment of ADHD to better characterize the clinical profile of the patient... To characterize further the phenotype of the patient during the diagnostic process that may deserve clinical attention, we suggest developing a tool based on the time estimation paradigm. The time estimation accuracy score not only represents an intuitive score reflecting faster internal clock mechanisms in individuals with ADHD, but the paradigm also shows high internal consistency and test-retest reliability, allowing for a reliable assessment of developmental or interventional changes in timing abilities related to developmental factors or external interventions."

Ivo Marx, Samuele Cortese, Michael G Koelch, Thomas Hacker, "Meta-analysis: Altered Perceptual Timing Abilities in Attention-Deficit/Hyperactivity Disorder," Journal of the American Academy of Child and Adolescent Psychiatry (2021), published online,https://doi.org/10.1016/j.jaac.2021.12.004.

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Evidence-Based Interventions for ADHD

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: 

  1. Choose an age group: children (6–17), adolescents (13–17), or adults (18+). 
  1. Choose a time frame: results at 12, 26, or 52 weeks. 
  1. Choose whether to explore by intervention (e.g., methylphenidate, CBT, mindfulness, diet, neurofeedback) or by outcome (e.g., ADHD symptoms, functioning, adverse events), depending on what’s available. EBI-ADHD Database 

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: 

  1. How big the effect is, compared to placebo or another control (large benefit, small benefit, no effect, small negative impact, large negative impact). 
  1. How confident we can be in that result (high, moderate, low, or very low certainty).  

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.” 

Meta-analysis Finds Tenuous Links Between ADHD and Thyroid Hormone Dysregulation

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.

 

December 15, 2025

Meta-analysis Finds Assisted Reproductive Techniques Associated with Offspring ADHD

Meta-analysis Finds Assisted Reproductive Techniques Associated with Offspring ADHD 

Background:

Recent progress in reproductive medicine has increased the number of children conceived via assisted reproductive techniques (ART). These include: 

  • In vitro fertilization (IVF), in which eggs are retrieved from the ovaries and fertilized with sperm in a laboratory; embryos are then transferred into the uterus.  
  • Intracytoplasmic sperm injection (ICSI), where a single sperm is injected directly into an egg. 
  • Intrauterine insemination (IUI), in which sperm is placed directly into the uterus around the time of ovulation. This is often combined with ovulation-inducing (OI) medications. 

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.

 

December 12, 2025