Gender Differences in Dynamic Functional Network Connectivity in Pediatric and Adult Patients with Attention-Deficit/Hyperactivity Disorder

Attention-deficit/hyperactivity disorder (ADHD) persistence into adulthood depends on gender, with 60% female and 35% male cases. This study sought to investigate gender differences in dynamic functional network connectivity (FNC) using resting-state functional magnetic resonance imaging data of pediatric ADHD patients (female: N = 24; 11.02 ± 2.60 years, male: N = 20;11.87 ± 2.62 years) and adult ADHD patients (female = 19; 31.11 ± 10.40 years, males: N = 20;32.05 ± 10.10 years). We identified nine and eight networks in pediatrics and adult data, respectively, using group independent component analysis (GICA). Each age group was clustered into four states using K-means. Significant gender differences in the pediatric group were only found in temporal profiles, particularly in "fraction of time"(FOT) and "mean dwell time"(MDT), but not in FNC. FOT spent by the female pediatric group in state 4 showed a negative relationship with hyperactivity severity. Compared with the adult male group, reduced connectivity was observed within the visual network (VN), between the VN and default-mode network (DMN), and frontoparietal network, as well as between the DMN and cerebellum networks in female adult ADHD patients. Significant FOT and MDT differences were observed between the two groups in state 3. Our results imply gender differences in ADHD, especially in the adult group. Furthermore, given the gender differences observed, our work provides insights into the pathophysiology of ADHD subserved by gender. Attention-deficit/hyperactivity disorder (ADHD) symptoms differ between genders; however, little has been done to determine gender differences in pediatric and adult ADHD patients. The present work presents the first gender-specific dynamic functional network connectivity study for different age groups of ADHD patients and highlights the discrepancies between male and female ADHD patients, particularly in the adult group, which may be due to the persistence of inattentive symptoms in female ADHD patients from childhood into adulthood. Given the gender differences observed in the current study, clinicians could consider treatment strategies that target each gender in each age group. The present work provides further insight into the connectivity patterns of the resting-state network in ADHD and may also serve as a basis for future sex-specific studies in different age groups in other disorders.