Honghui Yao

Background: Attention-deficit/hyperactivity disorder (ADHD) has been linked to elevated risk of type 2 diabetes (T2D). However, the impact of ADHD and ADHD medication use on prognosis and health outcomes in T2D remains unclear. This study investigates the associations of (1) ADHD and (2) ADHD medication use with rates of major adverse cardiac events (MACE) and all-cause mortality after a T2D diagnosis. Methods: This multinational cohort study used population-based data from Australia, Denmark, the Netherlands, Norway, Sweden, the United Kingdom, and the United States. Using a standardized analytical protocol, we identified adults with a first recorded T2D diagnosis during 2010-2020. Exposures were (1) ADHD, defined by a recorded ADHD diagnosis or ADHD medication dispensation, and (2) among adults with ADHD, the use of ADHD medication, both analysed as time-varying exposures. Main outcomes were MACE (acute myocardial infarction, stroke, or cardiovascular disease-related death) and all-cause mortality after T2D diagnosis. Cause-specific Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs); results were pooled using random-effects meta-analyses and stratified by age and sex. Results: The cohort included 1,929,027 adults with T2D (909,176 [47.1%] males). In pooled analyses, adults with T2D and ADHD had a higher rate of all-cause mortality (HR, 2.42; 95% CI, 1.72-3.41), but not MACE (HR, 1.04; 95% CI, 0.81-1.35), after a T2D diagnosis compared with those without ADHD. Among adults with T2D and ADHD, ADHD medication use was associated with higher rate of MACE in those diagnosed with T2D before age 45 years (HR, 1.58; 95% CI, 1.18-2.10). These associations remained consistent, after adjusting for sex, age, calendar year at T2D diagnosis, psychiatric history, other psychotropic medication use, and cardiometabolic medication use. Conclusions: Adults with T2D and co-occurring ADHD were found to have increased risk of all-cause mortality after T2D diagnosis, while ADHD was not consistently associated with MACE across countries. ADHD medication use was linked to higher rate of MACE in adults with early-onset T2D. These findings suggest the potential need for integrated somatic-psychiatric care and careful consideration of ADHD medication use that may help reduce MACE and mortality, particularly in younger-onset T2D.

The potential associations between parental ADHD and a broad spectrum of offspring health outcomes remain uncertain. We explored associations between parental ADHD and multiple adverse outcomes in offspring. We used linked Swedish national registers to identify all individuals born in Sweden between 2000 and 2014 ( N = 1,164,580) and followed them from birth until emigration, death, or December 31, 2020. After matching, 56,853 individuals with parental ADHD and 544,716 individuals without parental ADHD were included in the analysis. Parental ADHD was identified through ADHD diagnoses or ADHD medication prescriptions. Offspring of parents with ADHD were matched to ten individuals whose parents had no ADHD diagnosis. Stratified Cox regression models with robust standard errors were used to estimate associations between parental ADHD and 24 offspring outcomes. Offspring of parents with ADHD had higher rates of most adverse outcomes, compared with those without parental ADHD. Parental ADHD was associated with an increased rate of offspring psychiatric disorders (range of hazard ratios [HRs]: 1.49 for intellectual disability – 4.47 for ADHD), behavioral outcomes (range of HRs: 1.08 for falls – 1.82 for assault/victimization), and somatic disorders (range of HRs: 1.04 for type 1 diabetes–2.47 for sleep disorder). After adjusting for offspring lifetime ADHD, associations weakened but remained significant, except for intellectual disability and epilepsy. Rates were elevated for both maternal and paternal ADHD and highest when both parents with ADHD. Parental ADHD was associated with elevated risks of a broad range of adverse outcomes in offspring, encompassing psychiatric, behavioral, and somatic conditions. These findings highlight the broad intergenerational impact of ADHD and the need for early identification and family-focused preventive strategies.

Background: Early discontinuation of attention-deficit/hyperactivity disorder (ADHD) medication is common and linked to worse outcomes. Identifying clinical predictors could aid personalised treatment yet evidence is inconsistent across ages and countries/regions. Objective: Investigate psychiatric and neurological comorbidity as predictors of early ADHD medication discontinuation in new ADHD medication users across age groups, sex and countries/regions. Methods: Using health records from eight countries/regions, we identified 1 000 411 (44% female) new ADHD medication users (2011–2020). Discontinuation was defined as a ≥180 day gap between dispensations. We examined 23 indicators of psychiatric or neurological comorbidity, severity and psychotropic medication use. Associations were estimated using Cox regression, pooled with random-effects meta-analyses and stratified by age-at-initiation and sex. Findings: Discontinuation rates varied widely (children 19%–61%, adolescents 37%–68%, young adults 52–67%, adults 38%–68%). In pooled analyses, earlier discontinuation in children was predicted by intellectual disability, autism and use of psychotropic medications (HR range 1.32–1.51), while conduct/oppositional defiant disorder (CD/ODD) was protective (HR 0.83, 95% CI 0.73 to 0.94). In adolescents, no indicators remained statistically significant after multiple-testing control. In young adults, CD/ODD (HR 1.42, 95% CI 1.30 to 1.55), and in adults, schizophrenia (HR 1.25, 95% CI 1.09 to 1.44) and tic disorders (HR 1.27, 95% CI 1.11 to 1.46) predicted earlier discontinuation. Statistical heterogeneity was substantial, largely driven by US estimates. In meta-analyses excluding the USA, additional associations emerged. For example, in children, OCD and anxiety disorders predicted earlier discontinuation, while eating disorders and antidepressants/anxiolytics were protective in adults. Associations with schizophrenia, tic disorders and CD/ODD were no longer significant. Country-specific analyses showed similar association patterns, except in the USA, Hong Kong and the UK. Sex differences were limited. Conclusions: Children with neuropsychiatric comorbidity and related comedication are more likely to discontinue ADHD medication early, whereas few consistent predictors were seen from adolescence onwards. Marked cross-country variation, particularly in the USA, points to system-level influences on treatment patterns. Clinical implications: Improving ADHD medication persistence will require consideration of healthcare context and age-specific strategies, including close monitoring for children with complex neuropsychiatric profiles, and consideration of broader factors in adolescents and adults, where clinical predictors were limited.