August 1, 2021
The ENIGMA-ADHD Working Group published a second large study on the brains of people with ADHD in the American Journal of Psychiatry this month. In this second study, the focus was on the cerebral cortex, which is the outer layer of the brain.
ADHD symptoms include inattention and/or hyperactivity and acting impulsively. The disorder affects more than one in twenty (5.3%) children, and two-thirds of those diagnosed continue to experience symptoms as adults.
In this study, researchers found subtle differences in the brain's cortex when they combined brain imaging data on almost 4,000 participants from 37 research groups worldwide. The differences were only significant for children and did not hold for adolescents or adults. The childhood effects were most prominent and widespread for the surface area of the cortex. More focal changes were found in the thickness of the cortex. All differences were subtle and detected only at a group level, and thus these brain images cannot be used to diagnose ADHD or guide its treatment.
These subtle differences in the brain's cortex were not limited to people with the clinical diagnosis of ADHD: they were also present - in a less marked form - in youth with some ADHD symptoms. This second finding results from a collaboration between the ENIGMA-ADHD Working Group and the Generation Study from Rotterdam, which has brain images of, 2700 children aged 9-11 years from the general population. The researchers found more symptoms of inattention to be associated with a decrease in cortical surface area. Furthermore, siblings of those with ADHD showed changes to their cortical surface area that resembled their affected sibling. This suggests that familial factors such as genetics or shared environment may play a role in brain cortical characteristics.
This is the largest study to date to look at the cortex of people with ADHD. It included 2246 people with a diagnosis of ADHD and 1713 people without, aged between 4 and 63 years old. This is the second study published by the ENIGMA-ADHD Working Group; the first examined structures that are deep in the brain. The ADHD Working Group is one of over 50 working groups of the ENIGMA Consortium, in which international researchers pull together to understand the brain alterations associated with different disorders and the role of genetic and environmental factors in those alterations.
The authors say the findings could help improve understanding of the disorder. 'We identify cortical differences that are consistently associated with ADHD, by combining data from many research groups internationally. We find that the differences extend beyond narrowly-defined clinical diagnoses and are seen, in a less marked manner, in those with some ADHD symptoms and unaffected siblings of people with ADHD. This finding supports the idea that the symptoms underlying ADHD may be a continuous trait in the population, which has already been reported by other behavioral and genetic studies.'. In the future, the ADHD Working Group hopes to look at additional key features in the brain - such as the structural connections between brain areas - and to increase the representation of adults affected by ADHD, on whom limited research has been performed to date.
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.
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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.
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:
Despite these promising results, the study also highlighted several limitations:
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.
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This New York Times article, “5 Takeaways from New Research about ADHD”, earns a poor grade for accuracy. Let’s break down their (often misleading and frequently inaccurate) claims about ADHD.
The Claim: A.D.H.D. is hard to define/ No ADHD Biomarkers exist
The Reality: The claim that ADHD is hard to define “because scientists haven’t found a single biological marker” is misleading at best. While it is true that no biomarker exists, decades of rigorous research using structured clinical interviews and standardized rating scales show that ADHD is reliably diagnosed. Decades of validation research consistently show that ADHD is indeed a biologically-based disorder. One does not need a biomarker to draw that conclusion and recent research about ADHD has not changed that conclusion.
Additionally, research has in fact confirmed that genetics do play a role in the development of ADHD and several genes associated with ADHD have been identified.
The Claim: The efficacy of medication wanes over time
The Reality: The article’s statement that medications like Adderall or Ritalin only provide short-term benefits that fade over time is wrong. It relies almost entirely on one study—the Multimodal Treatment Study of ADHD (MTA). In the MTA study, the relative advantage of medication over behavioral treatments diminished after 36 months. This was largely because many patients who had not initially been given medication stopped taking it and many who had only been treated with behavior therapy suddenly began taking medication. The MTA shows that patients frequently switched treatments. It does not overturn other data documenting that these medications are highly effective. Moreover, many longitudinal studies clearly demonstrate sustained benefits of ADHD medications in reducing core symptoms, psychiatric comorbidity, substance abuse, and serious negative outcomes, including accidents, and school dropout rates. A study of nearly 150,000 people with ADHD in Sweden concluded “Among individuals diagnosed with ADHD, medication initiation was associated with significantly lower all-cause mortality, particularly for death due to unnatural causes”. The NY Times’ claim that medications lose their beneficial effects over time ignores compelling evidence to the contrary.
The Claim: Medications don’t help children with ADHD learn
The Reality: ADHD medications are proven to reliably improve attention, increase time spent on tasks, and reduce disruptive behavior, all critical factors directly linked to better academic performance.The article’s assertion that ADHD medications improve only classroom behavior and do not actually help students learn also oversimplifies and misunderstands the research evidence. While medication alone might not boost IQ or cognitive ability in a direct sense, extensive research confirms significant objective improvements in academic productivity and educational success—contrary to the claim made in the article that the medication’s effect is merely emotional or perceptual, rather than genuinely educational.
For example, a study of students with ADHD who were using medication intermittingly concluded “Individuals with ADHD had higher scores on the higher education entrance tests during periods they were taking ADHD medication vs non-medicated periods. These findings suggest that ADHD medications may help ameliorate educationally relevant outcomes in individuals with ADHD.”
The Claim: Changing a child’s environment can change his or her symptoms.
The Reality: The Times article asserts that ADHD symptoms are influenced by environmental fluctuations and thus might not have their roots in neurobiology. We have known for many years that the symptoms of ADHD fluctuate with environmental demands. The interpretation of this given by the NY Times is misleading because it confuses symptom variability with underlying causes. Many disorders with well-established biological origins are sensitive to environmental factors, yet their biology remains undisputed.
For example, hypertension is unquestionably a biologically based condition involving genetic and physiological factors. However, it is also well-known that environmental stressors, dietary
habits, and lifestyle factors can significantly worsen or improve hypertension. Similarly, asthma is biologically rooted in inflammation and airway hyper-reactivity, but environmental triggers such as allergens, pollution, or even emotional stress clearly impact symptom severity. Just as these environmental influences on hypertension or asthma do not negate their biological basis, the responsiveness of ADHD symptoms to environmental fluctuations (e.g., improvements in classroom structure, supportive home life) does not imply that ADHD lacks neurobiological roots. Rather, it underscores that ADHD, like many medical conditions, emerges from the interplay between underlying biological vulnerabilities and environmental influences.
Claim: There is no clear dividing line between those who have A.D.H.D. and those who don’t.
The Reality: This is absolutely and resoundingly false. The article’s suggestion that ADHD diagnosis is arbitrary because ADHD symptoms exist on a continuum rather than as a clear-cut, binary condition is misleading. Although it is true that ADHD symptoms—like inattention, hyperactivity, and impulsivity—do vary continuously across the population, the existence of this continuum does not make the diagnosis arbitrary or invalidate the disorder’s biological basis. Many well-established medical conditions show the same pattern. For instance, hypertension (high blood pressure) and hypercholesterolemia (high cholesterol) both involve measures that are continuously distributed. Blood pressure and cholesterol levels exist along a continuum, yet clear diagnostic thresholds have been carefully established through decades of clinical research. Their continuous distribution does not lead clinicians to question whether these conditions have biological origins or whether diagnosing an individual with hypertension or hypercholesterolemia is arbitrary. Rather, it underscores that clinical decisions and diagnostic thresholds are established using evidence about what levels lead to meaningful impairment or increased risk of negative health outcomes. Similarly, the diagnosis of ADHD has been meticulously defined and refined over many decades using extensive empirical research, structured clinical interviews, and validated rating scales. The diagnostic criteria developed by experts carefully delineate the point at which symptoms become severe enough to cause significant impairment in an individual’s daily functioning. Far from being arbitrary, these thresholds reflect robust scientific evidence that individuals meeting these criteria face increased risks for the serious impairments in life including accidents, suicide and premature death.
The existence of milder forms of ADHD does not undermine the validity of the diagnosis; rather, it emphasizes the clinical reality that people experience varying degrees of symptom severity.
Moreover, acknowledging variability in severity has always been a core principle in medicine. Clinicians routinely adjust treatments to meet individual patient needs. Not everyone diagnosed with hypertension receives identical medication regimens, nor does everyone with elevated cholesterol get prescribed the same intervention. Similarly, people with ADHD receive personalized treatment plans tailored to the severity of their symptoms, their specific impairments, and their individual circumstances. This personalization is not evidence of arbitrariness; it is precisely how evidence-based medicine is practiced. In sum, the continuous nature of ADHD symptoms is fully compatible with a biologically-based diagnosis that has substantial evidence for validity, and acknowledging symptom variability does not render diagnosis arbitrary or diminish its clinical importance.
In sum, readers seeking a balanced, evidence-based understanding of ADHD deserve clearer, more careful reporting. By overstating diagnostic uncertainty, selectively interpreting research about medication efficacy, and inaccurately portraying the educational benefits of medication, this article presents an overly simplistic, misleading picture of ADHD.
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