December 9, 2024

Taiwanese Population Study Finds Strong Association Between Cleft Lip and Palate and Subsequent ADHD

Congenital cleft lip and palate (CCLP) are birth defects associated with genetic and environmental factors. The latter include heavy maternal consumption of alcohol and fetal exposure to retinoid drugs derived from vitamin A. 

Methods:

Taiwan has an island-wide single-payer health insurance system that reaches over 99% of the population. To explore the relationship between CCLP and various psychiatric disorders including ADHD, a Taiwanese study team used the island’s National Health Insurance Research Database to identify all 1,158 children and adolescents with CCLP during a ten-year period. They matched them ten-to-one with 11,580 age and sex-paired controls without CCLP. 

Summary of Results:

Further adjusting for demographic data (income, residence) and family history of major psychiatric disorders, children and adolescents with CCLP were more than seven times more likely to be diagnosed with ADHD during the follow-up period than controls. Patients with both cleft palate and cleft lip were more than nine times more likely to be subsequently diagnosed with ADHD than controls. 

Patients with CCLP were also six times more likely to be diagnosed with autism spectrum disorder and more than seven times as likely to be diagnosed with schizophrenia as non-CCLP controls. They were also more likely to be diagnosed with bipolar disorder or major depressive disorder, but these results did not reach statistical significance. 

Conclusion:

This study highlights a significant association between congenital cleft lip and palate (CCLP) and an increased risk of developing ADHD, with CCLP patients being more than seven times as likely to be diagnosed with the disorder. Additionally, CCLP was linked to a higher prevalence of other psychiatric conditions, including autism spectrum disorder and schizophrenia. These findings underscore the importance of monitoring mental health in individuals with CCLP and call for further research into the risk factors connecting these birth defects with psychiatric disorders.

 

Hsiang-Hsuan Huang, Ju-Wei Hsu, Kai-Lin Huang, Tung-Ping Su, Tzeng-Ji Chen, Shih-Jen Tsai, and Mu-Hong Chen, “Congenital cleft lip and palate and elevated risks of major psychiatric disorders: A nationwide longitudinal study,” Clinical Child Psychology and Psychiatry (2023) online first, https://doi.org/10.1177/13591045231200665

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Inflammation and Childhood ADHD: Platelet-to-Lymphocyte Ratios

Dose-response Association Found Between Platelet-to-Lymphocyte Ratio (PLR) and Childhood ADHD

Recent research suggests that inflammation may play a role in ADHD. Inflammation, marked by elevated proteins and cytokines, affects brain development and structure. Evidence suggests it plays a role in the development of ADHD, making the study of inflammatory markers crucial. 

The platelet-to-lymphocyte ratio (PLR) is a cost-effective test for predicting outcomes of chronic inflammation and neuroimmune diseases. Studies show PLR may be an important inflammatory marker in the pathophysiology of ADHD in children. 

The Study:

A Chinese study team used the National Health and Nutrition Examination Survey (NHANES) database maintained by the National Center for Health Statistics of the United States to investigate the association between PLR and ADHD in children aged 6–14. 

The team identified ADHD through prescriptions of ADHD medications. 

After exclusions for missing information, the study encompassed 1,455 children. 

The authors adjusted for the following potential confounders: sex, age, race, poverty-to-income ratio, maternal age at childbirth, smoking during pregnancy, asthma, health insurance status, dietary inflammatory index, monocyte count, segmented neutrophil count, eosinophil count, and basophil count. 

They also split the PLR results into quartiles, with the first quartile having the lowest readings. 

Prescriptions of ADHD medications were twice as frequent among children in the second quartile as they were among children in the first quartile. They were four times as frequent among children in the third quartile than among children in the first quartile.  

Conclusion

The team concluded, “These findings further support the potential role of inflammation in the onset and development of ADHD, providing preliminary evidence for PLR as a potential biomarker for ADHD and suggesting its possible use in identifying high-risk populations. However, considering the limitations of this study, future research should be designed as larger-scale, prospective, multi-center randomized controlled trials to validate these findings and further explore the relationship between inflammatory mechanisms and ADHD.” 

In other words, this study suggests that while high PLR values may serve as a potential biomarker for ADHD, particularly in specific high-risk groups, further research is needed to confirm these findings and fully understand the role of inflammation in ADHD development. Larger, more robust studies will be crucial to validating PLR as a reliable tool for identifying at-risk populations.

April 15, 2025

Meta-analysis of Two Nationwide Population Studies Finds No Harm to Offspring from Taking ADHD Medications During Pregnancy

ADHD is the most prevalent neurodevelopmental disorder. Nearly 1% of pregnant women in the Nordic countries and more than 1% in the United States are prescribed ADHD medications, ranking these among the most commonly used medications during pregnancy. However, the safety of exposing a fetus to ADHD medications is still uncertain, prompting many expectant mothers to stop using them out of fear for their unborn child’s well-being. 

The Study:

A European research team conducted a comprehensive nationwide study on the safety of ADHD medications during pregnancy using populations from Sweden and Denmark. The Swedish population was studied first, followed by inclusion of a separate study of the Danish population. Results were then combined through meta-analysis. Nordic countries, with their single-payer national health insurance systems and national population registers, facilitate the tracking of residents’ health from birth to death, thus providing robust data for such studies. 

The team accounted for various potential confounders, including maternal age, year of delivery, whether the mother was a first-time parent, self-reported smoking during pregnancy, and any psychiatric history. They also considered psychiatric inpatient or outpatient treatment received within two years before pregnancy, as well as the dispensing of other psychotropic medications during pregnancy, including antidepressants, antipsychotics, antiseizure medications, and anti-anxiety medications. Additionally, they examined the highest level of maternal education and civil status at delivery (married or cohabiting compared to single, divorced, or widowed). 

Out of 861,650 Swedish children, 2,257 were exposed to ADHD medications during pregnancy. Another 3,917 were born to mothers who discontinued ADHD medications before pregnancy.  

Children exposed to ADHD medications had lower rates of ADHD, autism spectrum disorder, and overall neurodevelopmental disorders; however, none of these differences were significant. 

Limiting the analysis to siblings to control for family environmental influences and genetics likewise found no significant differences.  

A meta-analysis combining the Swedish results with a separately conducted nationwide population study in neighboring Denmark similarly found no significant differences between children exposed to ADHD medications during pregnancy and children born to mothers who discontinued ADHD medications before pregnancy. 

Conclusion:

The team concluded, “Overall, our study provides reassuring evidence that continuing ADHD medication during pregnancy does not increase the risk of long-term NDDs [neurodevelopmental disorders] in offspring." 

From Meds to Mindfulness: What Actually Works for Adult ADHD?

A new large-scale study has shed light on which treatments for attention-deficit/hyperactivity disorder (ADHD) in adults are most effective and best tolerated. 

Researchers analyzed 113 randomized controlled trials involving nearly 15,000 adults diagnosed with ADHD. These studies included medications (like stimulants and atomoxetine), psychological therapies (such as cognitive behavioral therapy), and newer approaches like neurostimulation.

The Findings

Stimulant medications (lisdexamfetamine and methylphenidate) as well as selective norepinephrine reuptake inhibitors (SNRI) (atomoxetine) were the only treatments that consistently reduced core ADHD symptoms—both from the perspective of patients and clinicians. It may be worth noting that atomoxetine, while effective, was less well tolerated, with more people dropping out due to side effects.

Psychological therapies such as CBT, mindfulness, and psychoeducation showed some benefits, but mainly according to clinician ratings—not necessarily from the patients themselves. Neurostimulation techniques like transcranial direct current stimulation also showed some improvements, but only in limited contexts and with small sample sizes. Interestingly, none of the treatments—medication or otherwise—made a clear impact on long-term quality of life or emotional regulation. 

Conclusion 

So, what does this mean for people navigating ADHD in adulthood? Stimulant medications remain the most effective treatment for managing ADHD symptoms day-to-day but nonstimulant medication are not far behind, which is good given the problems we’ve had with stimulant shortages. This study also supports structured psychotherapy as a viable treatment option, especially when used in conjunction with medication. 

The study emphasizes the importance of ongoing, long-term research and the need for treatment plans that are tailored to the individual ADHD patient– Managing adult ADHD effectively calls for flexible, patient-centered care.

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April 9, 2025