Factors associated with the severity of tuberous sclerosis complex-associated neuropsychiatric disorders (TAND) in tuberous sclerosis complex.

Research on tuberous sclerosis complex-associated neuropsychiatric disorders (TAND) in China remains limited. This study aimed to identify determinants of TAND severity to guide clinical management. This multicenter registry-based study included 42 patients with genetically confirmed TSC recruited from nine tertiary hospitals in Henan Province between April 2021 and April 2024. TAND severity was estimated at follow-up using a domain-based scoring framework informed by the TAND checklist. Demographic, epilepsy-related, and genetic factors were analyzed using group comparisons, interaction analysis, univariable linear regression, and hierarchical regression. Among 42 patients with TSC, 25 carried TSC2 mutations and 23 had active epilepsy. Total TAND scores were significantly higher in patients with active epilepsy than in seizure-free patients (p < 0.001), and in patients with TSC2 mutations than in those with TSC1 mutations (p = 0.002). A significant interaction between genotype and seizure status was observed for total TAND score (p = 0.038). In hierarchical regression, genotype remained an independent correlate of TAND severity, while each additional year of education was associated with a 1.306-point reduction in total TAND score. TSC2 mutation, active epilepsy, and lower educational attainment were associated with greater TAND severity. TSC2 mutation remained independently associated with greater TAND severity after adjustment for epilepsy-related variables, whereas higher educational attainment showed a protective association. These findings support the need for early TAND screening and targeted follow-up in clinically vulnerable patients with TSC.