Associação entre Transtorno do Déficit de Atenção e Hiperatividade (TDAH) e biomarcadores inflamatórios avaliados aos 18 anos em participantes da Coorte de Nascimentos de Pelotas de 2004

Abstract

Introduction: Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder with an estimated prevalence ranging from 6% to 10% in children and about 4% in adults. It is characterized by symptoms such as difficulty maintaining attention, hyperactivity, and impulsivity. Sex differences in prevalence show that boys are approximately twice as likely to be diagnosed with ADHD compared to girls. Recent evidence highlights the central role of inflammation in ADHD, with studies linking immune dysfunction, genetic polymorphisms, prenatal inflammatory exposures, and autoimmune conditions to altered brain development. Blood inflammatory markers, such as C-reactive protein (CRP), uric acid (UA), and albumin (ALB), are valuable tools for identifying inflammation and aiding in the diagnosis and monitoring of diseases. Furthermore, these biological markers often exhibit sex-specific associations. In particular, longitudinal analyses of ADHD trajectories and their relationship with inflammatory markers are essential for understanding how the disorder evolves and interacts with biological processes over time. These analyses help distinguish transient features from chronic manifestations, providing critical insights for more precise and effective interventions. Objective: This study tested the association between cumulative ADHD symptoms from childhood to adolescence and blood inflammatory markers at age 18. We also explored the moderating role of sex in this association among participants from the 2004 Pelotas Birth Cohort. Methods: Data from 2,926 participants were analyzed. ADHD symptoms were assessed at ages 6, 11, and 15 using the Strengths and Difficulties Questionnaire (SDQ) to construct symptom trajectories. Serum inflammatory markers—CRP, ALB, and UA—were measured at age 18. Associations and interactions with sex were tested using multiple linear regression analysis. Results and Discussion: Significant interactions between hyperactivity/inattention symptom trajectories and sex were identified for all inflammatory markers analyzed. The sex-specific associations between ADHD and inflammation may guide more personalized treatment approaches. In males, hyperactivity/inattention symptom trajectories were associated with UA levels, with the "consistently high" trajectory showing an association with higher UA levels. In contrast, no significant association between UA levels and symptoms was observed in females. Additionally, no statistically significant associations were found for CRP or ALB levels in either sex. These findings highlight an important interaction effect between sex and hyperactivity/inattention symptoms in the association with inflammatory biomarkers. Although the literature on specific interactions between ADHD, sex, and CRP, ALB, and UA levels remains limited, the results of this study are consistent with previous research. Prior studies suggest that elevated UA levels are associated with impulsivity traits, a common feature in psychiatric disorders with this profile. Conclusions: Overall, the findings reinforce the potential role of uric acid as a relevant biomarker in the context of ADHD, particularly in relation to hyperactivity and impulsivity traits. The sex-specific association observed in this study underscores the importance of future research to deepen our understanding of the relationship between UA levels and ADHD in different population subgroups.