Re-examining the risk for switch from unipolar to bipolar major depressive disorder in youth with ADHD: A long term prospective longitudinal controlled study

Background Recent studies have identified subthreshold forms of bipolar (BP)-I disorder and deficits in emotional regulation as risk factors for bipolar disorder in youth. The primary aim of this study was to investigate whether emotional dysregulation and subthreshold forms of BP-I disorder increase the risk for BP switches in ADHD youth with non-bipolar MDD. Methods We used data from two large controlled longitudinal family studies of boys and girls with and without ADHD. Subjects (N=522) were followed prospectively and blindly over an average follow up period of 11.4 years. Comparisons were made between ADHD youth with unipolar major depression (MDD) who did (N=24) and did not (N=79) switch to BP-I disorder at follow-up. Results The rate of conversion to BP-I disorder at follow up was higher in MDD subjects with subthreshold BP-I disorder at baseline compared to those without (57% vs. 21%; OR=9.57, 95% CI=1.62-56.56, p=0.013) and in MDD subjects with deficient emotional self-regulation (OR=3.54, 95% CI=1.08-11.60, p=0.037). Limitations The sample was largely Caucasian, so these results may not generalize to minority groups. The sample of youth with SED was small, which limited the statistical power for some analyses. Conclusions Switches from unipolar MDD to BP-I disorder in children with ADHD and MDD were predicted by baseline subthreshold BP-I disorder symptoms and baseline deficits in emotional regulation. More work is needed to assess whether these risk factors are operant outside the context of ADHD.