Cookie Preferences
By clicking, you agree to store cookies on your device to enhance navigation, analyze usage, and support marketing. More Info
Thank you! Your submission has been received!
Oops! Something went wrong while submitting the form.
January 10, 2023
Sex chromosome abnormalities are replication errors that produce an atypical number of sex chromosomes. Most people have 23 pairs of chromosomes for a total of 46. One pair is called the sex chromosome pair. It is either XX (for biological females) or XY (for biological males). The term 46,XY refers to a typical biological male and the term 46,XX refers to the typical biological female.
In rare cases a person may have only 45 chromosomes due to having only one sex chromosome, the X chromosome (45,X). Some people, rarely, have an extra sex chromosome and are designated: 47,XXX, 47,XXY, and 47,XYY. These rare sex chromosome differences occur in between 0.5 and 1.3 per 1,000 livebirths.
These differences have physical manifestations. For example, 45,X is associated with shorter height and abnormal development of the ovaries. The other three are associated with greater height. 47,XXX is associated with premature ovarian failure and 47,XXY with low testosterone.
A Danish and U.S. team used data from Denmark’s single-payer universal health insurance system to assess the association of these sex chromosome differences with the prevalence of ADHD.
They performed a case-cohort study. The source population was all 1,657,449 singleton births in Denmark between May 1, 1981, and Dec 31, 2008. The cases consisted of all 93,608 individuals in this population who were diagnosed with any of five psychiatric disorders, including ADHD. These were compared with a cohort consisting of 50,615 individuals randomly selected from the source population.
The combined population prevalence of these four sex chromosome differences was 1.45 per 1,000. 47,XXY was the most common, at 1.23 per 1,000, followed by 47,XYY at .82 per 1,000, then 47,XXX at .66 per 1,000. 45,X was by far the least common, at less than .23 per 1,000.
All four conditions were associated with significantly increased risk of ADHD:
These data are intriguing because we know there are sex differences in the prevalence of ADHD but the causes of those differences are unknown.
Given that ADHD is more common in boys than girls, one would have predicted that having an extra Y chromosome would increase risk for ADHD. That is the case here but we also see that having an extra X chromosome also increases risk, which means that the impact of sex chromosomes on ADHD is not straightforward.
Xabier Calle Sánchez, Simone Montalbano, Morteza Vaez, Morten Dybdahl Krebs, Jonas Byberg-Grauholm, Preben B Mortensen, Anders D Børglum, David M Hougaard, Merete Nordentoft, Daniel H Geschwind, Alfonso Buil, Andrew J Schork, Wesley K Thompson, Armin Raznahan, Dorte Helenius, Thomas Werge, and Andrés Ingason, “Associations of psychiatric disorders with sex chromosome aneuploidies in the Danish iPSYCH2015 dataset: a case-cohort study,” The Lancet Psychiatry (2023) 10(2):129-138, https://doi.org/10.1016/S2215-0366(23)00004-4.
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.
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.
Counting umbilical cord vessels is standard in prenatal ultrasounds and confirmed at birth. Single umbilical artery (SUA) occurs in about 1 in 200 cases, with roughly 10% associated with anomalies, including central nervous system defects. Isolated SUA (iSUA) means one artery is missing without other structural issues.
Research on SUA, especially isolated iSUA, and childhood neurodevelopmental disorders (NDD) is limited and inconclusive. iSUA is linked to preterm birth and small-for-gestational age (SGA), both of which are NDD risk factors.
This Norwegian nationwide population study aimed to assess NDD risk in children with iSUA at birth, the influence of sex, and how preterm birth and SGA mediate this relationship.
The nation’s universal single-payer health insurance and comprehensive population registries made it possible to analyze all 858,397 single births occurring from 1999 to 2013, with follow-up continuing through 2019. Among these cases, 3,532 involved iSUA.
After adjusting for confounders such as parental age, education, and maternal health factors, no overall link was found between iSUA and later ADHD diagnosis. However, females with iSUA had about a 40% higher risk of subsequent ADHD compared to those without iSUA, even after adjustment.
The authors concluded, “The present study indicates that iSUA is weakly associated with ID [intellectual disability] and ADHD, and these associations are influenced by sex. This association is mediated negligibly through preterm birth and SGA. The associations were not clinically significant, and the absence of associations of iSUA with other NDD is reassuring. This finding can be useful in the counseling of expectant parents of fetuses diagnosed with iSUA.”
_logo%201.svg)
