Comorbidity of ADHD and subsequent bipolar disorder among adolescents and young adults with major depression: A nationwide longitudinal study

Objectives: Previous studies have found that attention-deficit hyperactivity disorder (ADHD) in childhood and adolescence is associated with an increased risk of major depression and bipolar disorder in later life. However, the effect of ADHD comorbidity on the diagnostic conversion to bipolar disorder among patients with major depression is still uncertain. Methods: Using the Taiwan National Health Insurance Research Database, 58,023 subjects < 30 years of age who had major depression with (n = 1,193) or without (n = 56,830) ADHD comorbidity between the years 2000 and 2008 were enrolled in our study. Subjects who developed bipolar disorder during the follow-up to the end of 2011 were identified. Results: Adolescents and young adults who had major depression with ADHD comorbidity had an increased incidence of subsequent bipolar disorder (18.9% versus 11.2%, p < 0.001) compared to those without ADHD. Cox regression analysis showed that ADHD comorbidity was an independent risk factor (hazard ratio = 1.50, 95% confidence interval 1.30-1.72) predicting subsequent bipolar disorder among those with major depression, adjusting for demographic data and psychiatric comorbidities. Conclusions: Patients with comorbid diagnoses of major depression and ADHD had an increased risk of diagnostic conversion to bipolar disorder compared to those who had major depression alone. Further studies would be required to validate this finding and to investigate the possible underlying mechanisms.