November 27, 2023
Although there are numerous kinds of perfluoroalkyl substances (PFAS), the primary ones used in the manufacture of fluoropolymers are perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). Because of their strong water-repelling properties, fluoropolymers are used in stain repellents, polishes, paints, and other coatings, as well as in water-resistant outdoor clothing. They are long-lasting and therefore both pervasive in the home and environment and subject to accumulation in our bodies, especially in urbanized and industrialized areas. These substances can be passed from mother to child both through the placenta and through breastfeeding.
With support from the European Union, a large international team of European and North American researchers set out to investigate possible associations between early-life exposure to PFOS and PFOA and subsequent ADHD. They performed a meta-analysis on nine European population studies encompassing 4,826 mother-child pairs.
Participants were restricted to live-born single births with data on concentrations of PFOS and/or PFOA, and available information on ADHD diagnosis or symptoms.
Because a) some studies looked at maternal serum/plasma, others at maternal breast milk; b) timing of sample collection varied (first trimester, delivery); and c) children's levels during the first two years of life were unavailable (ethical constraints limit drawing blood samples from infants), the team used a validated pharmacokinetic model of pregnancy and lactation to estimate pre-and postnatal concentrations of PFASs in offspring.
The team adjusted for seven potential confounders: maternal pre-pregnancy body mass index, maternal age at delivery, maternal education, maternal smoking, number of previous children, duration of breastfeeding, and child sex.
With these adjustments, no association was found between estimated exposures to either PFOS or PFOA at birth, at three months, and at two years and subsequent diagnosis or symptoms of ADHD. While the raw data showed slightly higher odds for girls than for boys to develop ADHD with identical exposures, the differences were statistically non-significant.
Joan Forns, Marc-Andre Verner, Nina Iszatt, Nikola Nowack, Cathrine Carlsen Bach, Martine Vrijheid, Olga Costa, Ainara Andiarena, Eva Sovcikova, Birgit Bjerre Høyer, Jürgen Wittsiepe, Maria-Jose Lopez-Espinosa, Jesus Ibarluzea, Irva Hertz-Picciotto, Gunnar Toft, Hein Stigum, Mònica Guxens, Zeyan Liew, and Merete Eggesbø https://doi.org/10.1289/EHP5444.
Background
ADHD (Attention-Deficit/Hyperactivity Disorder) is one of the most studied neurodevelopmental conditions, with many clinical trials evaluating the effectiveness and safety of various medications. These trials, known as randomized controlled trials (RCTs), are considered the gold standard for assessing treatments. However, strict eligibility criteria often exclude many real-world patients, raising questions about whether the findings from these trials apply to everyday clinical settings.
Our latest study sheds light on this issue, revealing just how many individuals with ADHD might be excluded from RCTs and the impact this exclusion has on their treatment outcomes.
Method
Researchers used Swedish national registries to analyze data from 189,699 individuals diagnosed with ADHD who started medication between 2007 and 2019. They applied exclusion criteria from 164 international RCTs to identify who would have been considered ineligible for these trials in order to determine the proportion of individuals with ADHD who would not meet the eligibility criteria for RCTs.
Key Findings
Many Patients Are Ineligible for Clinical Trials:
Ineligible Patients Face Unique Challenges:
Higher Risk of Adverse Outcomes:
What This Means
These findings highlight a major gap between the controlled environments of clinical trials and the realities faced by individuals with ADHD in everyday life. While RCTs provide valuable insights, their restrictive criteria often exclude patients with more complex health profiles or co-existing conditions. This limits the generalisability of trial results, meaning that treatment guidelines based solely on RCTs may not fully address the needs of all patients.
Conclusion
This study demonstrated that a significant proportion of individuals with ADHD, particularly adults, do not meet the eligibility criteria for standard RCTs. These results emphasize the importance of bridging the gap between research settings and real-world applications. By recognizing and addressing the limitations of RCTs, we can work towards more equitable and effective ADHD treatment strategies for everyone.
Background:
Our understanding of Attention-deficit/hyperactivity disorder (ADHD) has grown and evolved considerably since it first appeared in the DSM-II as “Hyperkinetic Reaction of Childhood.” This study aimed to find the disorder’s placement within the modern psychopathology classification systems like the Hierarchical Taxonomy Of Psychopathology (HiTOP).
The HiTOP model aims to address limitations of traditional classification systems for mental illness, such as the DSM-5 and ICD-10, by organizing psychopathology according to evidence from research on observable patterns of mental health problems.. Is ADHD best categorized under externalizing conditions, neurodevelopmental disorders, or something else entirely? A recent study by Zheyue Peng, Kasey Stanton, Beatriz Dominguez-Alvarez, and Ashley L. Watts takes a closer look at this question using a symptom-focused approach.
The Study:
Traditionally, ADHD has been associated with externalizing behaviors, such as impulsivity and hyperactivity, or with neurodevelopmental traits, like cognitive delays. However, this study challenges the idea of placing ADHD into a single category. Instead, it maps ADHD symptoms across three major psychopathology spectra: externalizing, neurodevelopmental, and internalizing.
The findings reveal that ADHD symptoms don’t fit neatly into one box. For example, symptoms like impulsivity, poor school performance, and low perseverance were strongly associated with externalizing behaviors. On the other hand, cognitive disengagement (e.g., daydreaming, blank staring) and immaturity were closely linked to neurodevelopmental challenges. Interestingly, cognitive disengagement also showed ties to internalizing symptoms, such as anxiety or depression.
This research underscores the complexity of ADHD. Rather than treating ADHD as a single, unitary construct, the study advocates for a symptom-based approach to better understand and treat individuals. By acknowledging that ADHD symptoms relate to multiple psychopathology spectra, clinicians and researchers can move toward more nuanced classification systems and targeted interventions.
Conclusion:
Ultimately, this study highlights the need for modern systems to move beyond rigid categories and adopt a more flexible, symptom-focused framework for understanding ADHD’s place in psychopathology.
Exposure to heavy metals like lead, arsenic, mercury, cadmium, and manganese is known to harm developing nervous systems. However, past studies on whether heavy metals specifically increase the risk of ADHD have shown mixed results.
A research team from China (Gu et al., 2024) reviewed medical studies and conducted meta-analyses to better understand this issue.
The team included studies on children and teens, focusing on cohort studies, case-control studies, and cross-sectional studies. They only used articles written in English and required validated biomonitoring (like blood tests) to measure heavy metal exposure. ADHD diagnoses had to come from clinical evaluations.
To be included, studies had to report effect sizes such as odds ratios and relative risks with confidence intervals. The team focused on comparisons between groups with high, low, or no exposure, which made it harder to analyze dose-response relationships.
They also evaluated the quality of each study. All cohort studies were rated high-quality. Of the 15 case-control studies, 6 were high-quality, and 9 were moderate-quality. Among cross-sectional studies, only 2 were high-quality, and the rest were moderate-quality.
There was no evidence linking ADHD to other heavy metals like arsenic, mercury, cadmium, or manganese. Both meta-analyses suggest that lead exposure is associated with the risk for ADHD. However, because these studies cannot rule out other explanations, one cannot conclude that lead exposure causes ADHD. For example, other work shows that people with ADHD are likely to have lower incomes than those without ADHD.
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