July 4, 2021

Researchers have found the first risk genes for ADHD

Our genes are very important for the development of mental disorders-including ADHD, where genetic factors capture up to 75% of the risk. Until now, the search for these genes had yet to deliver clear results.   In the 1990s, many of us were searching for genes that increased the risk for ADHD because we know from twin studies that ADHD had a robust genetic component.  Because I realized that solving this problem required many DNA samples from people with and without ADHD, I created the ADHD Molecular Genetics Network, funded by the US NIMH.  We later joined forces with the Psychiatric Genomics Consortium (PTC) and the Danish psych group, which had access to many samples.  
The result is a study of over 20,000 people with ADHD and 35,000 who do not suffer from it - finding twelve locations (loci) where people with a particular genetic variant have an increased risk of ADHD compared to those who do not have the variant.  The results of the study have just been published in the scientific journal Nature Genetics, https://www.nature.com/articles/s41588-018-0269-7.
These genetic discoveries provide new insights into the biology behind developing ADHD. For example, some genes have significance for how brain cells communicate with each other, while others are important for cognitive functions such as language and learning.
Our study used the genome-wide association study (GWAS)methodology because it allowed us to discover genetic loci anywhere on the genome.  The method assays DNA variants throughout the genome and determines which variants are more common among ADHDvs. control participants.  It also allowed for the discovery of loci having very small effects.  That feature was essential because prior work suggested that, except for very rare cases, ADHD risk loci would individually have small effects.
The main findings are:

A) we found 12 loci on the genome that we can be certain harbor DNA risk variants for ADHD.  None of these loci were traditional candidate genes' for ADHD, i.e., genes involved in regulating neurotransmission systems that are affected by ADHD medications.  Instead, these genes seem to be involved in the development of brain circuits.  
B) we found a significant polygenic etiology in our data, which means that there must be many loci(perhaps thousands) having variants that increase the risk for ADHD.  We will need to collect a much larger sample to find out which specific loci are involved;

We also compared the new results with those from a genetic study of continuous measures of ADHD symptoms in the general population. We found that the same genetic variants that give rise to an ADHD diagnosis also affect inattention and impulsivity in the general population.  This supports prior clinical research suggesting that, like hypertension and hypercholesteremia, ADHD is a continuous trait in the population.  These genetic data now show that the genetic susceptibility to ADHD is also a quantitative trait comprised of many, perhaps thousands, of DNA variants
The study also examined the genetic overlap with other disorders and traits in analyses that ask the questions: Do genetic risk variants for ADHD increase or decrease the likelihood a person will express other traits and disorders.   These analyses found a strong negative genetic correlation between ADHD and education. This tells us that many of the genetic variants which increase the risk for ADHD also make it more likely that a person will perform poorly in educational settings. The study also found a positive correlation between ADHD and obesity, increased BMI, and type-2 diabetes, which is to say that variants that increase the risk of ADHD also increase the risk of overweight and type-2 diabetes in the population. This work has laid the foundation for future work that will clarify how genetic risks combine with environmental risks to cause ADHD.  When the pieces of that puzzle come together, researchers will be able to improve the diagnosis and treatment of ADHD.

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Meta-analysis Identifies Resilience Factors Associated with Improved Outcomes in Children and Adolescents with ADHD

Background:

While ADHD is generally linked to negative childhood outcomes, individual variability exists. Researchers have found that factors like cognition, emotion, parenting, and social interactions can help some adversity-exposed children develop better than expected. This variability has driven extensive resilience research, which now views resilience not as a single trait, but as a combination of biological, psychological, social, and ecological processes supporting adaptation. 

The Study:

This meta-analysis sought to address several key research gaps. First, while many potential resilience factors have been identified, no previous meta-analysis has quantitatively synthesized evidence focused specifically on children with ADHD. Second, relatively little research has clarified how particular resilience factors relate to specific developmental outcomes. Third, there is currently no integrated conceptual model of resilience processes tailored to children and adolescents with ADHD. 

To keep the analysis focused and clinically relevant, the authors examined psychosocial and ecological resilience factors only. Biological factors (such as genetics or cardiovascular health) and non-modifiable demographic characteristics (such as age and sex) were excluded, as they do not readily inform interventions. The analysis also focused strictly on outcomes for children and adolescents with ADHD, excluding adult outcomes and those reported for parents or teachers. Only studies based on clinical ADHD diagnoses were included. 

In total, 28 studies involving more than 11,600 participants met the inclusion criteria. Fifteen studies were rated as high quality and 13 as fair quality; none were rated low quality. However, the evidence base was relatively thin for many analyses. Of the 50 components examined, only one included five studies, six included four studies, ten included three studies, and most (33) were based on just two studies. While some components involved large samples, most did not, meaning the findings should be viewed as suggestive rather than definitive. 

Results:

Unsurprisingly, academic skills and cognitive functioning – specifically including working memory and intelligence – were strongly associated with better educational outcomes for children and adolescents with ADHD. In contrast, social skills and proactive attitudes or behaviors showed no significant link to educational attainment

Well-being outcomes showed a different pattern. Proactive attitudes and behaviors, cognitive functioning, and parental resources were associated with small-to-moderate improvements in well-being. Emotional regulation and positive parenting or attachment, however, were not significantly related to well-being in this analysis. 

For relationship outcomes, peer relationships – especially close friendships – stood out as particularly important, showing strong associations with better relational functioning. Social skills and positive parenting or attachment were linked to moderate improvements, although positive parenting alone had no significant effect. This suggests that the observed benefit likely stemmed from parental warmth and secure parent–child attachment rather than parenting practices in isolation. Parental resources (such as parental social support) and school-based support (including student–teacher relationships) showed no significant association with relationship outcomes. 

The study also examined behavioral symptoms. Externalizing symptoms refer to outward-directed behaviors that affect others or the environment, such as aggression, defiance, impulsivity, hyperactivity, and rule-breaking. Peer relationships were linked to a modest reduction in these behaviors, while positive relationships with adults were associated with a strong reduction. In contrast, disciplinary parenting – particularly harsh punishment – was strongly associated with increased externalizing symptoms. 

Internalizing symptoms involve inward-directed distress, such as anxiety, depression, withdrawal, excessive worry, and unexplained physical complaints. Here again, positive relationships with adults were important, showing a moderate association with fewer internalizing symptoms. Emotional regulation was also linked to small-to-moderate improvements. 

Conclusion: 

Overall, the findings highlight that resilience factors tend to be closely tied to specific outcomes rather than broadly protective across domains. For example, emotional regulation was associated with lower levels of both internalizing and externalizing symptoms but showed no significant link to well-being, educational achievement, or relationship quality. This suggests that emotional regulation may play a particularly important role in protecting mental health in children with ADHD, rather than driving broader developmental gains – consistent with evidence that emotional dysregulation is a core difficulty in ADHD. 

Similarly, academic skills, social competence, and prosocial behaviors were linked mainly to their most closely related outcomes. Cognitive functioning was associated with both educational and well-being outcomes, but its impact was much stronger in education and more modest for well-being. Together, these context-specific patterns underscore the importance of designing interventions that target particular resilience factors with strategies tailored to specific developmental goals, rather than assuming that any single factor will promote resilience across all areas of life. 

Key takeaway: resilience is individual and resilience isn’t one trait; different types of support help different individuals, in different areas.

Higher Relative Fat Mass (RFM) Associated with Lower ADHD Risk in Boys but Higher ADHD Risk in Girls

Background: 

Traditional measures of obesity, like body mass index (BMI) and waist circumference, have been linked to ADHD risk — but they aren’t great at capturing where fat is actually stored in the body. A newer index called relative fat mass (RFM), which combines height and waist circumference, does a better job of estimating overall body fat and predicting metabolic risks like heart disease and metabolic syndrome. Because those conditions share some underlying biological mechanisms with ADHD, researchers wondered whether RFM might also help explain the relationship between obesity and ADHD — particularly in children. 

That question is complicated by the fact that ADHD doesn't look the same in boys and girls. Boys tend to display more hyperactive and impulsive behavior, making their ADHD easier to spot. Girls more often show inattention, which is quieter and frequently goes undiagnosed. 


The Study: 

A new study set out to test whether RFM is associated with ADHD in children, and whether that association differs between sexes. Using data from the National Health and Nutrition Examination Survey (NHANES) collected between 1999 and 2004, the researchers narrowed a large initial pool of over 31,000 participants down to 5,089 children and adolescents aged 6 to 14 who had complete data on height, waist circumference, ADHD screening, and other relevant variables. 

After adjusting for age, race/ethnicity, Poverty-Income Ratio, maternal age at delivery, maternal smoking during pregnancy, health insurance coverage, and birth weight, the results revealed a striking split along sex lines.  

In boys, higher RFM was associated with lower odds of ADHD. Compared to boys in the lowest fat-mass quartile, those in the second quartile had about 10% lower odds of ADHD, rising to over 30% lower in the third quartile and nearly 40% lower in the highest. In girls, the pattern reversed entirely. While girls in the second quartile showed similar odds to those with the lowest RFM, girls in the third and fourth quartiles had 60% to 70% greater odds of ADHD. 

Conclusion & Why This Matters:  

In recent years, the relationship between obesity and ADHD has become an increasingly important focus in pediatric neurodevelopmental research. Studies have reported higher rates of ADHD symptoms among children and adolescents with obesity compared with their non-obese peers, and difficulties with peer relationships have also been linked to increased obesity risk (Sönmez et al., 2019). From a neurobiological standpoint, both conditions may involve shared underlying mechanisms, particularly dysfunction in dopaminergic pathways.

The authors concluded that higher body fat levels appear to lower ADHD risk in boys while raising it in girls. This finding highlights why sex-specific analysis matters in ADHD research. The underlying biological reasons for this divergence, however, remain an open question and open the door for future research. 

US Study Highlights the Social Roots of ADHD

While ADHD is a developmental disorder, shaped by biology and genetics, growing evidence shows that it is also influenced by the social and environmental conditions in which children grow up. Research on the social determinants of health emphasizes that development is shaped not only by biology but also by factors such as family income, access to healthcare, neighborhood safety, and material stability. These factors can affect both how developmental challenges appear and whether they are recognized and diagnosed. 

Children facing socioeconomic disadvantage consistently show higher risks of developmental and behavioral difficulties. Chronic stress linked to poverty – including financial strain, food insecurity, and limited access to resources – has been associated with problems in attention, emotional regulation, and daily functioning. Children from lower-income families also tend to experience more severe ADHD symptoms and face greater barriers to ongoing care. 

Neighborhood conditions matter as well. Unsafe environments can limit opportunities for play and social interaction while increasing caregiver stress, all of which may influence children’s behavior and development. Material hardships, such as food insecurity, can further undermine stability at home. 

The Study:

The study analyzed six years of data from the National Survey of Children’s Health (2018–2023), covering more than 205,000 U.S. children aged 3 to 17. After accounting for age, sex, race and ethnicity, region, family structure, survey year, and other social factors, the researchers found a strong income gradient in ADHD prevalence. Compared with children in households earning at least four times the federal poverty level, those in households earning two to four times that level had 28 percent higher odds of ADHD. Odds rose to 70 percent higher in households earning one to two times the poverty level, and more than doubled among children living below the poverty line. 

Parental education showed a similar pattern. Compared with children whose parents had completed college, ADHD odds were 20 percent higher among those whose parents had some college education, 40 percent higher among those whose parents had only a high school education, and 80 percent higher among those whose parents had not finished high school. 

Children living in unsafe neighborhoods had nearly twice the odds of ADHD compared with those in safe neighborhoods, and food insecurity was also linked to almost double the odds. 

By contrast, race and ethnicity alone were associated with much smaller differences. Compared with non-Hispanic White children, children in non-Hispanic Black households had an 18 percent higher likelihood of ADHD, while children in Hispanic households had a 25 percent lower likelihood. No substantial differences were observed for children from other or multiracial households. 

Conclusion and Takeaway:

The study team concluded, “Children living in lower-income households, experiencing food insecurity, and residing in unsafe neighborhoods consistently showed higher prevalence and higher adjusted odds of both conditions. … Overall, these findings reinforce the need to view neurodevelopmental disorders within a broader social and structural framework.” 

It should be noted that this study is not aiming to name social factors as direct causes of ADHD. Rather, it points to socioeconomic disparities as contributing to the way ADHD develops and how it is treated. This type of research, as well as acknowledging barriers to care, is crucial for clinicians, counselors, teachers, etc., to consider when working with youth with ADHD.