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January 16, 2024
Infants begin to transition from breast or formula milk to solid food at about six months of age, as they gradually develop interest in food and the ability to chew.
The American Academy of Pediatrics recommends breastfeeding for the first six months. The European Society of Pediatric Gastroenterology Hepatology and Nutrition recommends initiation of supplementary food around that time. The World Health Organization (WHO) has set a 2025 goal of getting most mothers worldwide to breastfeed exclusively through the first six months of infancy.
Noting that “inconsistent findings have been reported in previous national survey-based studies,” a South Korean study team conducted a nationwide population study to explore the relationship between breastfeeding and subsequent rates of ADHD.
South Korea has a mandatory single-payer national health insurance system – the National Health Insurance Service (NHIS) – that covers virtually the entire population. Detailed and consistent NHIS records facilitate nationwide population studies.
One NHIS program is the National Health Screening Program for Infants and Children (NHSPIC), which includes periodic examinations by trained pediatricians up to six years of age.
Using these national records, the team identified a cohort of over 1.1 million infants. These same records show that a little over a third (36%) received nothing but formula milk feeding during their first six months. About a fifth (21%) received a mix of formula and breast feeding. Almost a half (43%) were exclusively breastfed.
ADHD diagnoses were made by physicians during hospital visits.
The team adjusted for a series of confounders that were found to influence outcomes: sex, year of examination, residence, socioeconomic status, preterm birth, birth weight, and body measurements (weight, microcephaly) at examination (4–6 months of age).
With these adjustments, partial breastfeeding was associated with a small but significant (9%) reduction in the odds of infants later being diagnosed with ADHD, relative to infants receiving only formula milk feeding.
Exclusive breastfeeding was associated with a much larger 23% reduction in the odds of infants later being diagnosed with ADHD, relative to exclusive formula feeding.
What’s especially noteworthy is the dose-response pattern that suggests that breastfeeding may have a protective effect.
A separate analysis comparing infants who began transitioning to supplementary solid food before versus after six months found absolutely no difference in the odds of subsequently being diagnosed with ADHD.
A similar pattern emerged for autism spectrum disorder on all counts, again reflecting a dose-response pattern, pointing to what may be a broader beneficial effect of breastfeeding for healthy neurologic development.
The team concluded, “The risk of ADHD and ASD [autism spectrum disorder] considerably decreased with breastfeeding, and this tendency was more prominent in children who received EBF [exclusive breastfeeding] than in those who received PBF [partial breastfeeding]. Our study strengthens and supports the idea that breastfeeding is beneficial in preventing NDDs [neurodevelopmental disorders] in children. We suggest that breastfeeding be encouraged and recommended to promote good neurodevelopmental outcomes.”
Jong Ho Cha, Yongil Cho, Jin-Hwa Moon, Juncheol Lee, Jae Yoon Na, and Yong Joo Kim, “Feeding practice during infancy is associated with attention-deficit/ hyperactivity disorder and autism spectrum disorder: a population-based study in South Korea,” European Journal of Pediatrics (2023), https://doi.org/10.1007/s00431-023-05022-z.
Methylphenidate is an effective treatment for ADHD in adults who also have bipolar disorder (BD), but it carries a potential risk of triggering manic episodes. Current guidelines therefore recommend using it only alongside mood-stabilizing medication. A new study using French nationwide claims data sought to test and extend those recommendations with greater statistical power than previous research.
The study built on findings by Viktorin et al. (2017), who observed that adults with BD not taking mood stabilizers had more than a sixfold higher risk of manic events (defined as hospitalization for mania or a new antimanic prescription) within six months of starting methylphenidate. Patients on mood-stabilizing treatment, by contrast, showed nearly half the baseline risk in the first three months. Those findings were limited, however, by small event counts (fewer than 61 manic episodes) and an effect that did not persist beyond the initial three-month window.
To build on this, researchers drew on the French National Health Data System (which is a claims database covering more than 60 million people) spanning 2008 to 2024. The final sample included 6,022 adults with BD (56% women) who had started methylphenidate. Using a self-controlled design, the study compared each patient's rate of manic events in the six months before their first methylphenidate prescription with the rate in the six months after, effectively eliminating stable individual differences as a confound.
Patients were classified as receiving continuous mood-stabilizing treatment if they had been dispensed at least two courses of specific antipsychotics (aripiprazole, olanzapine, or quetiapine) or mood stabilizers (lithium or valproate) in the nine months before starting methylphenidate, including at least one dispensation in the final six months of that window.
The results largely confirmed the earlier findings. Among the 2,745 patients not on mood stabilizers, the rate of inpatient mania diagnosis was 5.1 times higher in the first three months after starting methylphenidate, though this elevation fell to a non-significant level over the subsequent three months. Patients receiving continuous mood-stabilizing treatment showed no statistically significant change in mania risk across the full six-month post-initiation period. A formulation-specific pattern also emerged: patients without mood-stabilizing treatment had a 2.5-fold higher risk associated with extended-release methylphenidate, while no significant risk increase was seen with the immediate-release formulation or in treated patients regardless of formulation.
The authors conclude that methylphenidate at doses below 30 mg does not appear to elevate manic relapse risk when prescribed alongside mood stabilizers. The elevated risk seen in untreated patients, particularly with extended-release formulations, must be interpreted cautiously, given limited statistical power and the likelihood that it partly reflects the natural fluctuation of manic relapse over time. The authors flag this as an inherent limitation of self-controlled survival analyses when studying drug-induced mania, where temporal trends in the underlying condition can be difficult to disentangle from treatment effects.
The FDA has approved a new once-daily pill called centanafadine (trade name SIMTRIYO®). Approved for adults and kids aged 6 and older (weighing at least 44 lbs / 20 kg), centanafadine is a new category of ADHD treatment that aims to give fast results with fewer of the downsides of traditional stimulants.
To understand why centanafadine is unique among medications for ADHD, it helps to look at how ADHD brain chemistry works:
Stimulants like Ritalin and Adderall work mainly in the dopamine system. Nonstimulants like atomoxetine, viloxazine, clonidine and guanfacine work mainly on the norepinephrine system. Centanafadine is the first drug in a new class called NDSRIs (Norepinephrine, Dopamine, and Serotonin Reuptake Inhibitors). We can describe its effects as follows:
What Did Clinical Trials Show?
The FDA approved centanafadine based on studies involving thousands of adults, teens, and children. Here are the key findings:
Centanafadine showed some improvement in ADHD symptoms within the very first week of taking it although a full effect takes about six weeks.
In adult trials, taking 200 mg or 400 mg daily led to significant improvements in real-world skills:
In trials with children (ages 6–12) and teens (ages 13–17), centanafadine significantly reduced core ADHD symptoms like hyperactivity, impulsivity, and lack of focus compared to a placebo.
About 30% to 40% of adults with ADHD also suffer from anxiety. Traditional stimulants can make anxiety worse. In a trial specifically designed for adults dealing with both ADHD and anxiety, centanafadine effectively treated ADHD symptoms without firing up their anxiety, which might be due to its serotonin boost.
Does Centanafadine have Side Effects?
While Centanafadine was well-tolerated by most people in studies, like any prescription medication, it comes with important safety guidelines.
Prescribing Warnings:
Common Side Effects:
Other Warnings:
The Bottom Line
Overall, centanafadine is a new step forward in how we treat ADHD. Because it acts differently in the brain than traditional treatments, patients who struggle with stimulant-related anxiety or side effects may find it useful to explore with their doctor.
A landmark nationwide study from South Korea has uncovered a significant link between prenatal exposure to air pollution — specifically nitrogen dioxide (NO2) — and an increased risk of ADHD in children.
While researchers have long suspected that air pollutants interfere with fetal brain development through inflammation and oxidative stress, this study is one of the largest and most comprehensive of its kind, following nearly 1.5 million births for up to 13 years.
Why South Korea?
South Korea provided a unique countrywide “laboratory” for this research due to two key infrastructure strengths:
Key Findings: The “Smoking Gun” of NO2
While the study looked at several pollutants, nitrogen dioxide — a byproduct of fossil fuel combustion in cars and power plants — emerged as the primary concern.
Pollutant
Association with ADHD Risk
Nitrogen Dioxide (NO2)
Strongest Link: Every 1-ppb (part-per-billion) increase in exposure linked to a 22% rise in risk.
Sulfur Dioxide (SO2)
Minimal Link: Only a slight 4% increase per ppb.
Ozone (O3) carbon monoxide (CO), & particulates
No significant association was found.
The scale of the NO2 risk is particularly striking. Over the typical range of exposure levels found in the study (an interquartile range of 13 ppb), the data suggest a threefold increase in ADHD risk for children in the highest-exposure groups compared to the lowest.
Accounting for Other Factors
To ensure the results weren’t skewed by other variables, the researchers controlled for a wide range of confounders including:
The authors emphasized the strong association between maternal nitrogen dioxide exposure and ADHD, while also noting the small but significant association with sulfur dioxide.
The Take-Away: A New Frontier for Public Health
Historically, air quality laws have been designed to protect our lungs and hearts. However, this study adds to a growing body of evidence suggesting that the brain is likewise vulnerable.
In a commentary on the findings, expert George Ayoub argued that “neurodevelopment should be explicitly considered” when governments perform cost-benefit analyses on air quality regulation. My view is a bit different. The association is intriguing but the study does not establish cause and effect. Many statistically significant environmental risk associations for neurodevelopmental disorders have disappeared after controlling for maternal risk for ADHD. I hope this research team will do those analyses if feasible.
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