Psychiatric Comorbidities and Schizophrenia in Youths With Attention-Deficit/Hyperactivity Disorder

IMPORTANCE: The association between attention-deficit/hyperactivity disorder (ADHD) and schizophrenia has received increased attention; however, evidence on the association between psychiatric comorbidities and subsequent schizophrenia in patients with ADHD is limited. OBJECTIVE: To investigate the risk of being diagnosed with schizophrenia in children and adolescents with ADHD considering the presence of psychiatric comorbidity. DESIGN, SETTING, AND PARTICIPANTS: This was a population-based, retrospective cohort study using the Health Insurance Review and Assessment claims database from January 1, 2007, to December 31, 2019. Participants were children and adolescents aged 5 to 19 years who received an ADHD diagnosis between January 1, 2010, and December 31, 2018, in the nationwide claims data of Korea. Data were analyzed from January 2010 to December 2019. INTERVENTIONS OR EXPOSURES: The presence of psychiatric comorbidity was assessed from diagnosis records within 1 year before ADHD diagnosis. Comorbidities were further categorized according to the number of comorbidities and specific comorbid disorders. MAIN OUTCOMES AND MEASURES: Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% CIs, examining the association between psychiatric comorbidities and the risk of being diagnosed with schizophrenia. Furthermore, the occurrence of psychiatric comorbidity during the follow-up period was explored among patients without psychiatric comorbidity at baseline. RESULTS: A total of 211 705 patients with newly diagnosed ADHD were included. A total of 157 272 patients (74.3%) were male, and the age of 5 to 9 years showed the highest distribution (115 081 patients [54.4%]). Patients with psychiatric comorbidity had a significantly higher risk of being diagnosed with schizophrenia than those without (adjusted HR, 2.14; 95% CI, 2.05-2.23). The association between schizophrenia and psychiatric comorbidity became progressively greater with the increasing number of comorbidities. Several individual psychiatric disorders showed an association with development of schizophrenia, with ASD, intellectual disability, tic disorder, depression, and bipolar disorder being the top 5 disorders most associated. Furthermore, 3244 patients (73.8%) without psychiatric comorbidities experienced the emergence of other psychiatric disorders before schizophrenia occurrence. CONCLUSIONS AND RELEVANCE: In this retrospective cohort study involving children and adolescents with ADHD, the presence of psychiatric comorbidity in patients with ADHD was associated with an increased risk of being diagnosed with schizophrenia, with an increased risk observed in multiple comorbidities and a wide variety of comorbidities. These findings highlight the significance of assessing and managing psychiatric comorbidities in patients with ADHD to decrease subsequent schizophrenia risk and allow for early intervention.