December 19, 2021
Polycystic ovary syndrome (PCOS) is a disorder affecting women of reproductive age, characterized by elevated levels of male hormones (androgens). The name is derived from the presence of cysts surrounding the ovum, which cause enlargement of the ovaries. Its cause remains unknown. There is speculation that high androgen levels could affect brain development in the fetus.
A team of Iranian researchers (Maleki et al.) published a twofold meta-analysis earlier this year exploring the relationship between PCOS and offspring ADHD. A systematic search of the peer-reviewed medical literature came up with six studies, consisting of three cohort studies, and three case-control studies.
A meta-analysis of the three case-control studies with a combined total of 79,978 participants found that children of mothers with PCOS were 42 percent more likely to develop ADHD.
A separate meta-analysis of the three cohort studies with a combined total of 325,435 participants produced essentially identical outcomes: children of mothers with PCOS were 43 percent more likely to develop ADHD.
There was no indication of publication bias in either meta-analysis and virtually no heterogeneity. Except for one case-control study, all studies were considered to be of high quality.
The authors concluded, "Our study showed that maternal PCOS is a risk factor for ADHD. Therefore, Screening for ADHD among children of these women should be considered as part of the comprehensive clinical care for women with PCOS."
More recently, a second-team (Dubey et al.), based in Texas, published a meta-analysis on the same subject. Their systematic search produced the same studies, but classified one study described as case-control by Malekiet al. as a cohort study.
Their meta-analysis of four cohort studies with a combined total of over two million participants (they counted participants differently than Maleki et al.) found that children of mothers with PCOS were 43 percent more likely to develop ADHD. Adjusting for confounders made no difference.
Again, there was no indication of publication bias, and between-study heterogeneity was virtually nil.
Considering they relied on the same studies, the fact that both teams reported identical outcomes is unsurprising, confirming there's a clear association between maternal PCOS and ADHD in offspring.
Pallavi Dubey, Bhaskar Thakur, Sheryl Rodriguez, JessikaCox, Sheralyn Sanchez, Anacani Fonseca, Sireesha Reddy, Deborah Clegg, and Alok Kumar Dwivedi, "A systematic review and meta-analysis of the association between maternal polycystic ovary syndrome and neuropsychiatric disorders in children" TranslationalPsychiatry (2021), 11:569, published online,https://doi.org/10.1038/s41398-021-01699-8.
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.
The Background:
Caffeine and its primary breakdown compounds – paraxanthine, theophylline, and theobromine (also the primary alkaloid in chocolate) – readily cross the placenta and tend to linger due to the underdevelopment of fetal caffeine metabolizing enzymes.
Could accumulating caffeine metabolites harm the developing fetal brain? Studies to date have come to contradictory conclusions, some finding an association, others finding none.
Norway has a national single-payer health insurance system with a national health registry comprehensively tracking virtually all residents.
The Methods:
An international study team used Norways’s registry, and its Mother, Father, and Child Cohort Study (MoBa) to explore the relationship between maternal and paternal coffee consumption and offspring neurodevelopmental difficulties (ND), including symptoms of ADHD as determined from validated rating scales, using 58,964 mother-child pairs and 22,576 father-child pairs, covering the decade 1999-2008.
Unadjusted results indicated a strong association between maternal coffee consumption before and during pregnancy with offspring ADHD, but none with paternal coffee consumption. Superficially, that might seem like compelling evidence.
Yet after adjusting for education, income, smoking, and alcohol, “previously significant effects attenuated towards zero and some associations switched from being positive to negative.”
Then, after further adjusting for genetic confounding, ADHD symptoms at 1.5 years, 3 years, 5 years (on both of two different rating scales), and 8 years (including separate measures of inattention and hyperactivity symptoms) all became indistinguishable between offspring from mothers consuming coffee during pregnancy and offspring of mothers abstaining from coffee during pregnancy.
Conclusion:
The team concluded, “This study applied several conventional and genetic epidemiological approaches to investigate the potential relationship between maternal coffee consumption during pregnancy and offspring NDs [neurodevelopmental difficulties]. When considering the results of the conventional and genetic epidemiological analyses, as well as the broader literature, we conclude that there is little evidence that maternal coffee consumption during pregnancy is strongly causally related to offspring NDs.”
More specifically, the team found no evidence of any causal relationship with offspring ADHD.
_logo%201.svg)
