Although rare, childhood- or adolescent-onset schizophrenia is frequently associated with significantly more deleterious clinical and functional prognoses compared to adult-onset schizophrenia (Coulon et al., 2020; Diaz-Caneja et al., 2015; Hollis, 2000). Neurodevelopmental disorders (NDDs)—encompassing autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD)—are increasingly recognized as significant antecedents that confer an elevated liability for subsequent psychotic disorders (Maibing et al., 2015; Nourredine et al., 2021; Varcin et al., 2022). For example, children diagnosed with ADHD demonstrate an estimated 4∼5-fold increase in the odds of manifesting a psychotic disorder compared to their neurotypical peers (Nourredine et al., 2021). Furthermore, meta-analytic estimates suggest that approximately 9 % of individuals with ASD present with comorbid psychotic disorder in adulthood (Varcin et al., 2022)—a prevalence magnitude significantly exceeding the ∼1 % rate observed in the general population. Notably, a comprehensive Danish registry study reported that adolescents diagnosed with any antecedent psychiatric disorder exhibited 8.7 % cumulative incidence of schizophrenia-spectrum disorders over 8-years follow-up period, in contrast to the 1∼2 % incidence observed in age-matched controls without early diagnoses (Maibing et al., 2015). Collectively, these data delineate youth with neurodevelopmental or psychiatric conditions as a phenotypically “risk-enriched” population for schizophrenia, notwithstanding the fact that only a minority will ultimately undergo transition to overt psychosis.

However, applying population-level risk estimates to individualized prognostic assessments in clinical practice remains a significant practical challenge. While existing registry studies often lack clinical specificity, research focusing on the "Clinical High Risk" (CHR) state primarily recruits help-seeking individuals presenting with attenuated psychotic symptoms rather than those with pre-established NDDs. (Collins et al., 2023; Hartmann et al., 2024; Lang et al., 2022; Lee et al., 2022). Consequently, a critical gap remains regarding the elucidation of the "natural history" of psychosis risk among children managed for NDDs within routine tertiary clinical settings. Furthermore, in many Western cohorts, the transition from NDD to psychosis is heavily confounded by adolescent substance abuse, obscuring the intrinsic neurobiological trajectory.

To address these gaps, we investigated the clinical transition risk within a Korean tertiary care cohort. This study is distinguished by two methodological strengths: (1) the utilization of an Internal Clinical Control Group to mitigate the ascertainment bias inherent to specialized referral centers, and (2) the leveraging of the unique sociocultural context of South Korea, where adolescent illicit substance use is negligible which allows for the isolation of neurodevelopmental trajectories with minimal confounding from substance confounding.