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.

How Early Parent–Child Interactions May Shape the Expression of ADHD Traits: A Longitudinal Study

We know that Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition with strong biological and genetic underpinnings; However, emerging research suggests that early environmental influences—particularly parent–child interactions—may shape how ADHD traits, such as impulsivity and delay aversion, are expressed during development.

This longitudinal study explored whether negative parental reactions during moments of delay contribute to the intensification of ADHD-related behaviors in preschool-aged children. A total of 112 mother–child pairs from the UK and Hong Kong participated. Children were screened for ADHD traits using the Strengths and Difficulties Questionnaire, ensuring a range of symptom severity. 

The experimental task—the Parent–Child Delay Frustration Task (PC-DeFT)—was designed to assess how children responded to brief, unpredictable waiting periods during a game-like activity, and how parents reacted in turn. During the task, children operated a button to change a red light to green, allowing their parent to retrieve a toy item. While most trials had no delay, six included unexpected 5–10 second pauses, creating mild frustration. Trained observers recorded children’s behavioral responses and parents' emotional reactions.

At follow-up (12–18 months later), teacher ratings revealed that children whose parents showed more negative reactions during delay trials (e.g., impatience, criticism) were more likely to exhibit increases in ADHD traits—especially impulsivity and difficulty waiting. Importantly, this link was mediated by increases in delay aversion, a motivational style where the child seeks to avoid frustrating waiting experiences. No such associations were found in free play or non-delay tasks, underscoring the specificity of this interaction.

The study’s findings suggest that, while these interactions do not cause ADHD, early social environments can influence how and when symptoms manifest. Interventions aimed at supporting positive parent–child interactions—particularly in challenging contexts like waiting—may help shape the developmental trajectory of children predisposed to ADHD.

May 15, 2025

Study Finds LSD Microdosing No More Effective Than Placebo For ADHD

Double-blind Randomized Clinical Trial Finds LSD Microdosing No More Effective Than Placebo in Treating ADHD Symptoms

Background:

Stimulants, such as methylphenidate and amphetamines, are currently considered effective medications for treating ADHD. However, approximately one-third of patients do not have an adequate response to these treatments. Additionally, long-term adherence is relatively low, with only about half of the patients still using methylphenidate after six years. 

Recently, there has been increasing attention to the concept of microdosing with psychedelic drugs such as psilocybin and LSD. A microdose typically ranges from one-tenth to one-twentieth of a recreational dose and does not produce noticeable perceptual effects or interfere with daily activities.  

The Study:

A European research team recently published the findings of the first double-blind, placebo-controlled randomized clinical trial examining the safety and efficacy of repeated low doses of LSD in adults diagnosed with ADHD. 

The six-week trial took place at University Hospital in Basel, Switzerland, and Maastricht University, Netherlands. Participants, aged 18 to 65, had clinical diagnoses of ADHD with moderate to severe symptoms.  

The team excluded persons with a past or present diagnosis of psychotic disorders, substance use disorders, or other psychiatric or somatic disorders likely to require hospitalization or treatments. 

Participants were randomly assigned in a 1:1 ratio to receive either LSD or placebo. Neither study staff nor participants were aware of the assignments until the conclusion of the trial. 

During the six-week trial, participants received twice-weekly doses on-site, amounting to a total of 12 doses. Following the first and final doses, participants were asked to determine whether they had been administered LSD or a placebo in order to assess blinding. Four weeks after the conclusion of the microdosing period, participants returned for an evaluation of the treatment's safety and efficacy. 

Twenty-seven of the 53 participants were randomized to receive the LSD microdosing treatment in a liquid solution, and 26 to receive placebo. Placebo consisted of the same drinking solution, minus the microdose of LSD. 

The average age was 37, and 42% of participants were female. Forty-six of the 53 participants completed the study. 

Out of 29 participants, 21 from the LSD group and eight from the placebo group correctly guessed their allocation, totaling 63% overall.  

As assessed through the Adult ADHD Investigator Symptom Rating Scale, ADHD symptoms improved by 7.1 points in the LSD group and 8.9 points in the placebo group, with no significant difference between them. 

Regarding safety, the LSD group experienced nearly double the adverse events compared to the placebo group. None of the events in either group were classified as serious. The five most frequent adverse events were headache, nausea, fatigue, insomnia, and visual alterations, occurring around three times more frequently in the LSD group than in the placebo group. 

The team concluded, “although repeated low-dose LSD administration was safe in an outpatient setting, it failed to demonstrate efficacy compared with placebo in improving ADHD symptoms among adults.” 

Conclusion: Microdosing with LSD did not offer significant advantages over placebo in treating ADHD symptoms, despite being physically safe and well tolerated in the trial setting. This suggests that further research is needed to explore alternative treatments for ADHD.

------

Struggling with side effects or not seeing improvement in your day-to-day life? Dive into a step-by-step journey that starts with the basics of screening and diagnosis, detailing the clinical criteria healthcare professionals use so you can be certain you receive an accurate evaluation. This isn’t just another ADHD guide—it’s your toolkit for getting the care you deserve. This is the kind of care that doesn’t just patch up symptoms but helps you unlock your potential and build the life you want. Whether you’ve just been diagnosed or you’ve been living with ADHD for years, this booklet is here to empower you to take control of your healthcare journey.

Proceeds from the sale of this book are used to support www.ADHDevidence.org.

Get the guide now– Navigating ADHD Care: A Practical Guide for Adults

April 23, 2025

Acupuncture for ADHD: A Promising Alternative or Placebo? A Look at Recent Research

Attention Deficit Hyperactivity Disorder (ADHD) is a common condition affecting children and adolescents worldwide, characterized by symptoms such as hyperactivity, impulsivity, and inattention. While traditional treatments like medication and behavioral therapy are often used, some individuals are turning to complementary and alternative therapies (CAM) for help. One such option gaining attention is acupuncture. But does it really work for ADHD?

A recent comprehensive study aimed to evaluate the effectiveness of acupuncture in treating ADHD symptoms. Here’s a breakdown of the findings, with a focus on the age groups included in the research and what these findings could mean for ADHD treatment options.

What the Study Explored

The study in question conducted a systematic review and meta-analysis (SR/MA) of acupuncture trials for ADHD, comparing its effects to traditional treatments such as pharmacotherapy and behavioral therapy. The researchers focused on acupuncture’s impact on core ADHD symptoms like hyperactivity, impulsivity, inattention, and conduct problems, while also exploring how acupuncture might help with other issues, such as learning difficulties and psychosomatic symptoms.

One key feature of this study was the inclusion of a broad age range of participants, specifically children and adolescents. These two groups are the most commonly diagnosed with ADHD, and their responses to treatments can vary significantly. Understanding how acupuncture works for these age groups is critical for evaluating its effectiveness as an ADHD treatment.

Here’s what the study found across the different age groups:

  • Children: Acupuncture appeared to be particularly effective in reducing hyperactivity and impulsivity in younger children with ADHD. These symptoms, often more prominent in younger populations, responded well to acupuncture when used alongside other treatments like medication.

  • Adolescents: For adolescents, acupuncture seemed to improve both hyperactivity and inattention, two symptoms that can often become more challenging as children grow older. This age group also benefited from acupuncture’s ability to reduce side effects from ADHD medications, such as irritability or sleep disturbances.

  • Combined Effects for Both Groups: When acupuncture was used in combination with pharmacotherapy, it also helped reduce side effects such as sleep problems and appetite loss in both children and adolescents. This could make it an attractive adjunctive treatment for those already on medication but experiencing undesirable effects.

  • Inattention and Conduct Problems: For both children and adolescents, acupuncture used in conjunction with either medication or behavioral therapy showed notable improvements in inattention and conduct problems—two of the most difficult symptoms of ADHD to manage.

  • Learning Difficulties and Psychosomatic Symptoms: Interestingly, the combination of acupuncture and medication provided significant improvements in learning difficulties, which are particularly relevant for children with ADHD. Meanwhile, acupuncture paired with behavioral therapy had a positive impact on psychosomatic symptoms, such as anxiety or stress, that often co-occur with ADHD.

Despite these promising results, the study also highlighted several limitations:

  • Study Quality Issues: The quality of the studies reviewed was often low, with many trials lacking the rigorous controls needed for high confidence in their results. For example, only a small number of trials used objective ADHD diagnostic tools, which could lead to biases in assessing acupuncture’s effectiveness.

  • Need for More Research: There is a lack of large-scale, high-quality randomized controlled trials (RCTs) comparing acupuncture with placebo treatments, which makes it hard to determine whether acupuncture’s effects are truly therapeutic or simply a placebo.

Conclusion: Is Acupuncture a Good Option for ADHD?

In short, and as is so often the way of evidence-based medicine, we still can’t say with absolute certainty one way or the other. These studies may show promise in improving hyperactivity, impulsivity, inattention, and conduct problems– in both children and adolescents. However, the evidence is not yet strong enough to recommend it as a primary treatment. While it may serve as a helpful complement to standard therapies, especially for those struggling with medication side effects or access to behavioral therapy, more research is needed to establish its effectiveness.

April 21, 2025