December 15, 2025

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.

 

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Hong Wang, Kun Huang, Lizhen Piao, and Xiaochen Xue, “Dysregulation of Thyroid, Growth, and Appetite Hormones in Children and Adolescents With Neurodevelopmental Disorders: A Meta-analysis,” Journal of Integrative Neuroscience (2025) 24(10), 39816,  https://doi.org/10.31083/JIN39816. 

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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. 

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July 14, 2025

Combined meta-analysis and nationwide population study indicates ADHD by itself has negligible effect on risk of type 2 diabetes

Study Indicates ADHD By Itself Has Negligible Effect on Risk of Type 2 Diabetes

Noting that “evidence on the association between ADHD and a physical condition associated with obesity, namely type 2 diabetes mellitus (T2D), is sparse and has not been meta-analysed yet,” a European study team performed a systematic search of the peer-reviewed medical literature followed by a meta-analysis, and then a nationwide population study.

Unlike type 1 diabetes, which is an auto-immune disease, type 2 diabetes is believed to be primarily related to lifestyle, associated with insufficient exercise, overconsumption of highly processed foods, and especially with large amounts of refined sugar. This leads to insulin resistance and excessively high blood glucose levels that damage the body and greatly lower life expectancy.

Because difficulty with impulse control is a symptom of ADHD, one might hypothesize that individuals with ADHD would be more likely to develop type-2 diabetes. 

The meta-analysis of four cohort studies encompassing more than 5.7 million persons of all ages spread over three continents (in the U.S., Taiwan, and Sweden) seemed to point in that direction. It found that individuals with ADHD had more than twice the odds of developing type 2 diabetes than normally developing peers. There was no sign of publication bias, but between-study variability (heterogeneity) was moderately high.

The nationwide population study of over 4.2 million Swedish adults came up with the same result when adjusting only for sex and birth year. 

Within the Swedish cohort there were 1.3 million families with at least two full siblings. Comparisons among siblings with and without ADHD again showed those with ADHD having more than twice the odds of developing type 2 diabetes. That indicated there was little in the way of familial confounding.

However, further adjusting for education, psychiatric comorbidity, and antipsychotic drugs dropped those higher odds among those with ADHD in the overall population to negligible (13% higher) and barely significant levels. 

The drops were particularly pronounced for psychiatric comorbidities, especially anxiety, depression, and substance use disorders, all of which had equal impacts.

The authors concluded, “This study revealed a significant association between ADHD and T2D [type 2 diabetes] that was largely due to psychiatric comorbidities, in particular SUD [substance use disorders], depression, and anxiety. Our findings suggest that clinicians need to be aware of the increased risk of developing T2D in individuals with ADHD and that psychiatric comorbidities may be the main driver of this association. Appropriate identification and treatment of these psychiatric comorbidities may reduce the risk for developing T2D in ADHD, together with efforts to intervene on other modifiable T2D risk factors (e.g., unhealthy lifestyle habits and use of antipsychotics, which are common in ADHD), and to devise individual programs to increase physical activity. Considering the significant economic burden of ADHD and T2D, a better understanding of this relationship is essential for targeted interventions or prevention programs with the potential for a positive impact on both public health and the lives of persons living with ADHD.”

Swedish Twin Study Finds Association Between Diet and ADHD

Associations between diet and ADHD emerge from Swedish population-based twin study

Sweden has a national single-payer health insurance system that includes virtually the entire population. It also has a system of national registers that track every resident from birth to death. That makes it possible to conduct nationwide population studies with a very high degree of precision and reliability.

In addition, one of the national registers is the Swedish Twin Register. Tracking all twins in the population enables studies to evaluate the degree to which observed associations may be attributable to genetic influences and to familial confounding. The twin method relies on the different levels of genetic relatedness between monozygotic ("identical") twins, who are genetically identical, and dizygotic ("fraternal") twins, who share on average half of their genetic variation (as do ordinary full siblings).

A Swedish team of researchers identified 42,582 Swedish twins born between 1959 and 1985, and who were, therefore, adults by the time of the study (20-47 years old). Of these, 24,872 (three out of five) completed a web-based survey with 1,300 questions covering lifestyle and mental and physical health. Out of this group, 17,999 provided information on ADHD symptoms and food frequency.

Self-reported ADHD symptoms came from nine inattention components and nine hyperactivity/impulsivity components, covering the 18 DSM- IV symptoms of ADHD.

The food frequency questionnaire included 94 food items, with the following frequency categories: never, 1-3 times/month, 1-2 times/week, 3-4 times/week, 5-6 times/week, 1 time/day, 2 times/day, 3 times/day.

In the raw data, the two subtypes of ADHD exhibited very similar associations. Both had significant associations with unhealthy diets. Both were more likely to be eating foods high in added sugar, and neglecting fruits and vegetables while eating more meat and fats.

After adjusting for the degree of relatedness of twins (whether monozygotic or dizygotic) and controlling for the other ADHD subtype, the associations remained statistically significant for inattention, but diminished to negligible levels or became statistically non-significant for hyperactivity/impulsivity.

Even for persons with inattention symptoms, adjusted correlations were small (never exceeding r = 0.10), with the strongest associations being for overall unhealthy eating habits (r = 0.09), eating foods high in added sugar (r = 0.10) or high in fat (r = 0.05), and neglecting fruits and vegetables (r = 0.06). All other associations became statistically non-significant.

For persons with hyperactivity/impulsivity symptoms, the only associations that remained statistically significant ­- but at tiny effect sizes - were unhealthy dietary patterns (r = 0.04) and consumption of foods high in added sugar (r = 0.03).

The further genetic analysis, therefore, focused on the strongest associations, between ADHD subtypes on the one hand, and unhealthy dietary patterns and eating foods high in added sugar on the other hand. The heritability estimates (the fraction of phenotypic covariance explained by genetic influences) were 44%, 40%, and 37% for inattention and high-sugar food, inattention and unhealthy dietary patterns, and hyperactivity/impulsivity and high-sugar food, respectively.

 When examining only differences between pairs of monozygotic("identical") twins, the correlations became stronger for inattention, rising to r = 0.12 for unhealthy eating habits and r = 0.13 for consumption of foods high in added sugar. For hyperactivity/impulsivity symptoms, the association with unhealthy eating habits was weaker, and the association with consumption of foods high in added sugar became statistically insignificant.

The authors concluded, "we identified positive associations between self-reported trait dimensions of ADHD and intake of seafood, high-fat food, high-sugar food, high-protein food, and an unhealthy dietary pattern, and negative associations with consumption of fruits, vegetables, and a healthy dietary pattern. However, all the associations are small in magnitude. These associations were stronger for inattention compared to hyperactivity/ impulsivity. This pattern of associations was also reflected at the etiological level, where we found a slightly stronger genetic correlation between inattention with dietary habits and hyperactivity/impulsivity with dietary habits. Non-shared environmental influences also contributed to the overlap between ADHD symptom dimensions and consumption of high-sugar food and unhealthy dietary pattern. However, shared environmental influences probably contributed relatively little to the associations between ADHD symptoms and dietary habits. ... significant MZ twin intraplate differences also provided support for a potential causal link between inattention and dietary habits.

November 29, 2021

Meta-analysis Finds Association Between Maternal Polycystic Ovary Syndrome (PCOS) and ADHD in Offspring

The Background:

Women with polycystic ovary syndrome (PCOS) themselves show higher rates of ADHD. Because ADHD is partly heritable (meaning genes contribute to the condition), some of the increased ADHD seen in children of mothers with PCOS could come from shared genetic factors. In other words, a mother’s and her child’s increased risk might sometimes reflect common genes rather than an effect of the pregnancy itself. 

Beyond genetics, growing evidence points to maternal metabolic problems during pregnancy as another important risk factor for neurodevelopmental outcomes. PCOS is one of these conditions and is considered both potentially modifiable (treatable or manageable) and biologically plausible as a contributor to risk. PCOS affects an estimated 5–10% of women of reproductive age worldwide and is characterized by signs such as hyperandrogenism (higher-than-normal levels of “male” hormones), insulin resistance (poorer ability to use the hormone insulin, which can affect blood sugar and metabolism), and chronic low-grade inflammation. 

However, studies to date have not all reached the same conclusions. Some research suggests the association between maternal PCOS and offspring ADHD is stronger for girls, while other studies did not analyze results by child sex. Methodological differences make it harder to draw clear conclusions. 

The Study:

It’s important to note that the studies included in this meta-analysis were observational (cohort studies and case-control studies). Observational studies can identify associations (that two things occur together) but cannot prove that one causes the other. A cohort study follows people over time, and a case-control study compares people with a condition to similar people without it. 

The pooled results came from six studies that together included almost 1.4 million mother–child pairs and that adjusted for confounders (other factors that might influence the result, such as maternal age or socioeconomic status). After statistical adjustment, children of mothers with PCOS had about 40% greater odds of ADHD than children of mothers without PCOS. The analysis reported no evidence of publication bias (no clear sign that only positive studies were published) and zero heterogeneity (the results were consistent across the studies). 

There was no meaningful difference in results between cohort and case-control studies, and the meta-analysis did not find a significant difference in the association when comparing male and female offspring. 

The Take-Away:

The research team concluded that this large-scale synthesis found an association between maternal PCOS and higher odds of ADHD and other neuropsychiatric conditions in children. They suggested that children born to mothers with PCOS may benefit from developmental monitoring to identify and address problems early, while emphasizing that causal relationships have not been established. They called for further studies to confirm these findings and to investigate the biological and environmental mechanisms that might explain the association. Indeed, because women with PCOS show higher rates of ADHD than other women, we need genetically informed research designs to see if the reported association is confounded.

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October 1, 2026

Large Cohort Study Finds Dose-Response Association Between Food Insecurity and ADHD

The Background:

Food insecurity is a widespread public‑health problem. Food insecurity refers to limited or uncertain access to enough safe, nutritious food. This term is used to describe households that sometimes or often can’t afford enough food or can only buy cheaper, less‑healthy options. 

In the United States, almost eleven million children and teens (14%) lived in food‑insecure households in 2019. By 2023, the share of households with food‑insecure children and adolescents was estimated to have risen to about 18%. 

Food insecurity is linked to worse physical health in children, including conditions like anemia (low red‑blood‑cell count), asthma, and delays in physical or mental development. It is also associated with problems in thinking and conduct (for example, aggressive behavior, anxiety, depression, and trouble concentrating or sitting still). 

Those thinking and behavior problems can look a lot like ADHD (persistent patterns of inattention, hyperactivity, and impulsivity. This can make it hard for clinicians to tell whether symptoms come from ADHD itself, from the stress of poverty and food insecurity, or a mix of both. That overlap can complicate diagnosis and sometimes lead to misdiagnosis. 

Smaller recent studies have looked at mental‑health links and found higher odds of ADHD and other mental‑health conditions among food‑insecure children aged 5–11 years. In one set of findings, moderate food insecurity was associated with 50% greater odds of an ADHD diagnosis and severe food insecurity with about 67% greater odds relative to food‑secure children. 

The Study:

Because many past studies looked at single risk factors or only measured symptom severity, fewer investigations have focused specifically on household food insecurity as it relates to actual ADHD diagnoses and how that might matter for care. To address that gap, researchers used multiple years (2016–2022) of data from the U.S. National Survey of Children’s Health (NSCH). This survey is designed to be nationally representative and asks parents about their child’s health, including whether a doctor or other clinician has diagnosed ADHD. 

The study included 232,571 children and adolescents (ages 3–17) and used statistical methods to adjust for other factors that could affect ADHD risk. Those factors included the child’s sex and race/ethnicity; the mother’s age; family income expressed as a percentage of the federal poverty level (a government measure used to classify income groups); the highest level of parent education; adverse childhood experiences (such as exposure to abuse, household substance use, or parental separation); birthweight (for example, low birthweight); and not getting enough sleep. Adjusting for these variables helps isolate the association between food insecurity and ADHD, though it cannot prove cause and effect. 

The Results:

In this large, nationally representative sample, the researchers found a clear dose–response relationship: as the level of household food insecurity increased, so did the odds of a child having a clinician‑diagnosed ADHD (as reported by parents). In other words, greater food insecurity was linked to a higher likelihood of ADHD. 

Compared with children in households that “could always afford to eat good, nutritious meals” (the reference group), the study found the following increases in odds of ADHD: children in households that “could always afford enough to eat but not always the kinds of food we should eat” had about 30% greater odds; children in households that sometimes “could not afford enough to eat” had about 55% greater odds; and children in households that often “could not afford enough to eat” had about 80% greater odds. (Saying “30% greater odds,” etc., means the odds were 1.30, 1.55, and 1.80 times those of the reference group, respectively — this describes a relative increase, not the absolute percentage of children with ADHD.) 

The Take-Away:

The authors conclude that household food insecurity was associated with higher odds of parent‑reported clinician‑diagnosed ADHD in a dose‑response pattern. They suggest that reducing food insecurity (for example, ,by improving access to nutritious food and combining nutritional supports with mental‑health care) may help lower ADHD risk or reduce symptoms in some children. Reducing food insecurity should be a priority for society, but it is premature to conclude it will reduce the risk for ADHD. We know that parents with ADHD are more likely to lose their jobs and have lower incomes compared to parents with ADHD.  That might create food insecurity for their children who we know are at high risk for ADHD from genetic studies.  

 

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Meta-analysis Finds Long-term Exercise Associated with Moderate Improvements in Executive Functioning for Children and Adolescents with ADHD

The Background: 

Many studies have tried to determine whether exercise improves executive function in children and adolescents with ADHD, but their conclusions have not always agreed. To bring the evidence together more clearly, the research team re-analyzed the available randomized controlled trials using a statistical approach designed to handle the kinds of data common in this field. 

Executive functions are skills that help us control attention and behavior. The three core components are inhibitory control (the ability to stop or override impulses), working memory (holding and manipulating information in mind), and cognitive flexibility (switching between tasks or perspectives). Because a single study often reports multiple tests that tap these different skills, one study can contribute several related results (called effect sizes). Traditional meta-analysis typically treats each effect size as independent; when they are actually correlated, that can bias the combined estimate or force reviewers to discard useful data. 

To avoid those problems, the team used a three-level meta-analysis. In this model, variance in the data is separated into three sources: 

(1) sampling variance: the random error in each measured effect 

(2) within-study variance: differences between multiple effect sizes reported in the same study

(3) between-study variance: differences in effects from one study to another

Accounting for all three levels makes it possible to include every eligible effect size from each study, which preserves information and statistical power and reduces the risk that correlations among effect sizes will overstate results. 

The Study:

The review focused on long-term exercise interventions and also tested whether certain factors might change (or moderate) the effects. These potential moderators included participant age, which executive-function subcomponent was measured, the type of exercise, how long each session lasted, the total length of the intervention, and how often sessions occurred. 

To be included, studies had to be randomized controlled trials (RCTs) of children or adolescents aged 6–18 diagnosed with ADHD. RCTs randomly assign participants to an intervention or a comparison group and are considered a strong design for testing cause-and-effect. The exercise programs had to be structured and last at least six weeks. Comparison groups varied by study and could include usual care, medication, sedentary activities, health education, waiting lists, or everyday life without the specific exercise program. Fifteen studies including 658 participants met these criteria. 

The Results:

The three-level meta-analysis showed that long-term exercise interventions were associated with moderate-to-strong improvements in overall executive function. When statistical outliers were removed, the result remained positive: 13 RCTs with 598 participants showed moderate improvements. In plain terms, this suggests improvements that are noticeable and meaningful on average, not just tiny changes that are unlikely to matter in daily life. 

Those moderate gains appeared across all three executive-function domains  (inhibitory control, working memory, and cognitive flexibility, meaning the benefits were not limited to a single cognitive skill. The authors also examined exercise type: 

“Open-skill” activities, which require reacting to changing situations (for example, many team sports, martial arts sparring, or racket sports), produced moderate-to-large improvements. 

“Closed-skill” activities, which are more predictable and repetitive (for example, running or stationary cycling), showed only small, non-significant improvements in this analysis. 

The review also found dose-related patterns. Interventions lasting at least twelve weeks were about three times more effective than interventions of six to twelve weeks, and sessions longer than an hour were about twice as effective as shorter sessions. Benefits were largest among adolescents aged 13 and older. 

These patterns suggest that longer, more intensive programs, and those that involve open-skill activities, may produce larger gains. However, the authors caution that the overall certainty of the evidence was low. “Low certainty” means that limitations in the available studies (for example, small sample sizes, variability in methods, or possible bias) make it difficult to be confident that the observed effects will hold up exactly the same way in future research. Some subgroup findings (age, intervention duration, and others) were based on only a small number of effect sizes, so those moderator results should be treated as exploratory rather than definitive. 

The Take-Away:

In short, this three-level meta-analysis suggests that regular, structured exercise (particularly longer programs and open-skill activities) may help improve executive functions in children and adolescents with ADHD. The evidence is promising but not yet strong enough to be considered conclusive, and the authors recommend more, larger randomized trials to confirm specifically which types and doses of exercise are most effective.  Moreover, neither this meta-analysis or others show that exercise can replace standard treatments for reducing the core symptoms of ADHD (inattention, hyperactivity, impulsivity).

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September 11, 2026