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.
There has been consistent evidence of an association between ADHD and subjectively reported sleep problems even in patients not medicated for the disorder. There have also been studies using wrist-worn actigraphy (a wrist watch-like device that measures gross motor activity) and sleep lab-based polysomnography that measure objective sleep parameters.
What has been missing are large population-based cohort studies to explore the prevalence rates of different sleep disorders and medical prescriptions in ADHD.
Methods Used:
Sweden has a single-payer health insurance system and a series of national population registers that track virtually its entire population. Using the Swedish Total Population Register, a local research team created a cohort of all 6,470,658 persons born between 1945 and 2008. They linked this to the Swedish National Patient Register, which includes inpatient hospitalizations from 1975 to 2013, and outpatient specialist diagnoses from 2001 to 2013, to identify diagnoses of sleep disorders. They also linked to the Prescribed Drug Register, covering 2005 to 2013, to identify prescriptions for sleep medications.
Summary of Findings:
Overall, persons with ADHD were eight times more likely to be diagnosed with any sleep disorder relative to normally developing peers. Broken down by age, adolescents with ADHD were 16 times more likely to receive such diagnoses, young adults (18-30) twelve times more likely, children and mid-age adults (31-45) eight times more likely, and older adults six times more likely.
Broken down by specific sleep disorder diagnoses, relative to normally developing peers, persons with ADHD were:
As for sleep medication, relative to normally developing peers, persons with ADHD were:
Conclusion:
The team concluded, “Our findings also suggest that greater clinical attention should be directed towards addressing sleep problems in individuals with ADHD. This entails implementing proactive measures through sleep education programmes and providing both pharmacological and non-pharmacological approaches such as cognitive behavioural therapy and parental sleep training.”
Attention is a critical determinant of academic achievement, influencing domains such as language, literacy, and mathematics. To explore whether physical activity can improve attention in children with ADHD, an international team conducted a meta-analysis of peer-reviewed studies. The goal was to evaluate the impact of various physical activity regimens on attention-related outcomes in this population.
The researchers performed a comprehensive search of the medical literature to identify studies examining the effects of physical activity on attention in schoolchildren with ADHD. They included 10 studies with a total of 474 participants in their meta-analysis. The studies evaluated two main types of physical activity:
Additionally, they examined variations based on the frequency, duration, and type of control groups used in the studies. To assess consistency, they also analyzed heterogeneity (variability of outcomes) and checked for potential publication bias.
Key findings from the meta-analysis include:
The authors concluded that mentally engaging exercise is more effective than aerobic exercise in improving attention problems in schoolchildren with ADHD. Furthermore, higher frequency and longer duration of physical activity do not necessarily yield better outcomes.
This research underscores the importance of tailoring physical activity interventions to emphasize cognitive engagement over intensity or duration. By refining strategies, educators and parents can better support children with ADHD in achieving academic success. But take note: given the results from controlled studies, it seems clear that if there is a positive effect of exercise, it is very small so should not replace standard treatments for ADHD.
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Previous studies have examined how stimulant medications affect the brain in controlled settings, but less is known about their impact in real-world conditions, where children may not always take their medication consistently or may combine it with other treatments. A new study leverages data from the Adolescent Brain Cognitive Development (ABCD) study to explore how real-world stimulant use impacts brain connectivity and ADHD symptoms over two years.
Changes in Brain Connectivity Researchers used brain imaging data from the ABCD study to examine the functional connectivity—communication between brain areas—of six regions within the striatum, a brain area involved in motivation and movement control. They focused on how stimulant use influenced connectivity between the striatum and other networks involved in executive functioning and visual-motor control.
The study found that stimulant exposure was linked to reduced connectivity between key striatal areas (such as the caudate and putamen) and large brain networks, including the frontoparietal and visual networks. These changes were more pronounced in children taking stimulants compared to those who were not medicated, as well as compared to typically developing children. Importantly, this reduction in connectivity seemed to regulate certain brain networks that are typically altered in children with ADHD.
Symptom Improvement In addition to brain changes, 14% of children taking stimulants experienced a significant reduction in ADHD symptoms over the two-year period. These children showed the strongest connectivity reductions between the right putamen and the visual network, suggesting that stimulant-induced connectivity changes may contribute to improvements in visual attentional control, which is a common challenge for children with ADHD.
Why This Matters This study is one of the first to examine how stimulant use in real-world conditions affects brain networks in children with ADHD over time. The findings suggest that stimulants may help normalize certain connectivity patterns associated with ADHD, particularly in networks related to attention and control. These insights could help clinicians better understand the potential long-term effects of stimulant treatment and guide personalized approaches to ADHD management.
Conclusion Stimulant medications appear to alter striatal-cortical connectivity in children with ADHD, with some changes linked to symptom improvement. This research highlights the potential for stimulant medications to impact brain networks in ways that support attention and control, highlighting the importance of understanding how real-world medication use influences ADHD treatment outcomes.
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