January 10, 2023

Danish population study: Sex chromosome abnormalities increase risk of ADHD

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:

  • 47,XXY roughly doubled the risk. 
  • 47,XXX increased the risk 2.5-fold.
  • 47,XYY more than quadrupled the risk.
  • 45,X more than sextupled the risk.

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.

Related posts

No items found.

Population Study Finds Strong Association Between Assisted Reproductive Technologies and Offspring ADHD

Taiwanese Nationwide Population Study Finds Strong Association Between Assisted Reproductive Technologies and Offspring ADHD

Background: 

Since the first in vitro fertilization (IVF) in 1978, assisted reproductive technology (ART) has led to over 10 million births worldwide.  

There are four types of embryo transfers, depending on whether they are fresh or frozen, and on their developmental stage. 

Fresh cleavage stage embryos are transferred on day 2 or 3 following fertilization and typically contain four to eight relatively large, undifferentiated cells. Fresh blastocyst embryos are transferred on day 5 or 6 after fertilization. At this point, they have developed over a hundred cells and have differentiated into two types: the inner cell mass, which develops into the fetus, and the outer cell layer, which forms the placenta. 

Globally, more children are now born through assisted reproductive technology using frozen-thawed embryo transfer than fresh embryo transfer.  

Research suggests that ART-conceived offspring may face increased risks of cardiovascular, musculoskeletal, chromosomal, urogenital diseases, and cancers. Might they also be at increased risk for ADHD? 

Study:

Taiwan’s single-payer health insurance covers over 99% of people and records all their healthcare activity. Since 1998, it has kept an ART database for all couples registered for IVF treatment. 

A Taiwanese research team reviewed all records for the five-year period from 2013 through 2017, ultimately analyzing 3,125 live singleton births from fresh cleavage stages, 1,332 from fresh blastocysts, 1,465 from frozen cleavage stages, and 4,708 from frozen blastocysts, alongside 878,643 naturally conceived singleton births. 

The team controlled for the following potential confounders: pregnancy-induced hypertension, chronic hypertension, diabetes mellitus, gestational diabetes mellitus, unhealthy lifestyle, placenta previa, placenta abruption, preterm premature rupture of membrane, and postpartum hemorrhage. 

Results:

With these adjustments, cleavage stage embryo transfers, whether fresh or frozen, were associated with a seven-fold higher rate of ADHD diagnosis in offspring than natural conception. 

Frozen blastocyst embryo transfers were likewise linked to a seven-fold increase in ADHD diagnoses in offspring compared to natural conception. Notably, fresh blastocyst transfers showed a 19-fold increase, likely due to the smaller number of cases in this category. 

The team concluded, “Compared to natural conception, ART is associated with higher risks, particularly for preterm birth, ADHD, and developmental delay.” 

Conclusion: 

This large national cohort suggests that ART-conceived singletons face higher rates of several adverse outcomes, including preterm birth, ADHD, and developmental delay. Clinicians and prospective parents should therefore weigh these potential associations when counseling and planning care, prioritize optimized ART protocols and perinatal management, and ensure early developmental surveillance for ART-conceived children so concerns can be identified and addressed promptly.

It is important to note that the findings also point to the likely contribution of underlying parental infertility in these developmental outcomes. Future research should aim to disentangle parental- versus procedure-related risks to clarify absolute risk magnitudes. As always, associations of this time should not be interpreted as causal due to the inability of observational studies to rule out all possible confounding factors.

October 1, 2025

Why Do So Many Young People Miss an ADHD Diagnosis? Insights from a New Study

Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental conditions, yet many young people, especially girls, receive a diagnosis late or not at all. This matters, because a delayed diagnosis often means missed opportunities for support, treatment, and improved long-term outcomes. A recent study by Barclay and colleagues (2024) sheds new light on why ADHD recognition is inconsistent, and what we can do about it.

The Study:

Researchers analyzed data from nearly 10,000 children in the UK Millennium Cohort Study. They compared children whose ADHD was recognized early (ages 5–7), later (ages 11–14), or not recognized at all, despite evidence of symptoms. The team also looked at differences between boys and girls to better understand why diagnosis patterns vary by sex.

Key Findings:
  1. Severity Drives Earlier Recognition
    Children who were diagnosed at a younger age often had more visible difficulties: emotional outbursts, peer conflict, conduct issues, and lower cognitive scores. In other words, the “louder” and more disruptive the symptoms, the more likely ADHD was flagged early.

  2. “Quieter” ADHD May Be Overlooked
    Children with stronger prosocial skills or higher cognitive ability were less likely to be recognized, even if they had clear ADHD symptoms. These children may be able to “mask” their difficulties, or adults may misinterpret their struggles as personality quirks rather than signs of ADHD.

  3. Emotional Dysregulation Matters
    Emotional dysregulation—big swings in mood, difficulty calming down, intense frustration—was strongly linked to recognized ADHD in boys, but not in girls. This suggests that clinicians may pay closer attention to these behaviors in boys, while overlooking them in girls.

  4. Co-occurring Conditions Can Influence Diagnosis
    Children with autism were more likely to have their ADHD identified. On the flip side, those who engaged in more physical activity were slightly less likely to be recognized, though the reasons for this are not yet clear.

What This Means for Clinicians:

The study highlights the importance of looking beyond the “classic” hyperactive child stereotype when considering ADHD. Clinicians should:

  • Pay attention to symptoms of emotional dysregulation, even if they are not part of standard diagnostic checklists.

  • Consider ADHD in children with good grades or strong social skills if other symptoms are present.

  • Be mindful of gender differences, since girls may be more likely to internalize symptoms or present with inattentiveness rather than hyperactivity.

What This Means for Parents and Patients:

If you’re a parent, it’s important to trust your observations. If your child struggles with focus, organization, or emotional regulation—even if they are doing well academically or socially—these could still be signs of ADHD. Advocating for an evaluation can make a big difference.

Moving Forward

This study makes clear that ADHD is not one-size-fits-all. Recognition often depends on how symptoms show up, how disruptive they appear, and even the child’s gender. By broadening our awareness and refining our screening practices, we can ensure that fewer children slip through the cracks and more receive the support they need early in life.

September 30, 2025

ADHD Medication and Academic Achievement: What Do We Really Know?

Parents and teachers often ask: Does ADHD medication actually improve grades and school performance? The answer is: yes, but with important limitations. Medications are very effective at reducing inattention, hyperactivity, and impulsivity but their impact on long-term academic outcomes like grades and test scores is not as consistent.

In the Classroom

The medications for ADHD consistently: Improve attention, reduce classroom disruptions, increase time spent on-task and help children complete more schoolwork and homework. Medication can help children with ADHD access learning by improving the conditions for paying attention and persisting with work.

Does Medication Improve Test Scores and Grades?

This is where the picture gets more complicated.  Medications have  stronger effect on how much work is completed but a weaker effect on accuracy. Many studies show that children on medication attempt more problems in reading, math, and spelling, but the number of correct answers doesn’t always improve as much. Some studies find small but significant improvements in national exam scores and higher education entrance tests during periods when children with ADHD are medicated.

Grades improve, as well, but modestly. Large registry studies in Sweden show that students who consistently take medication earn higher grades than those who don’t. However, these gains usually do not close the achievement gap with peers who do not have ADHD.

Keep in mind that small improvements for a group as a whole mean that some children are benefiting greatly from medication and others not at all.  We have no way of predicting which children will improve and which do not. 

Medication Alone Isn’t Enough

Academic success depends on more than just reducing inattention, hyperactivity and impulsivity. Skills like organization, planning, studying, and managing long-term projects are also critical.  Medication cannot teach these skills.

So, in addition to medication, the patient's treatment program should include educational support (tutoring, structured study skills programs), behavioral interventions (parent training, classroom management strategies), and accommodations at school (extra time, reduced distractions, organizational aids) Parents should discuss with their prescriber which of these methods would be appropriate.

Conclusions 

ADHD medication is a powerful tool for reducing symptoms and supporting learning. It improves test scores and grades for some children, especially when taken consistently. But it is not a magic bullet for academic success. The best results come when medication is combined with educational and behavioral supports that help children build the skills they need to thrive in school and beyond.

September 17, 2025