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

Abstract

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.

Can manic switches be predicted in pediatric major depression? A systematic literature review

“…In the first study by Biederman et al (2009a), the investigators reported that subthreshold symptoms of mania were significantly overrepresented in children with ADHD who developed bipolar-I disorder at follow-up compared with those who did not (70% vs 17%, p¼ .002). A subsequent report by Biederman et al (2013) using data from the same sample reported a significantly increased risk for manic switches in ADHD children with baseline MDD with subthreshold symptoms of mania when compared with those without such symptoms (57% vs 21%;OR¼9.57, p¼.013).…”

“…Children with CHT also displayed a wider range of aggressive behavior and a higher rate of suicidality (suicidal ideation in 81% vs 36%, po .05). Likewise, Biederman et al (2013) reported that ADHD children with deficient emotional self-regulation (defined by 41SD and o2SD elevations in the Anxiety/ Depression, Aggression, and Attention subscales of the CBCL) had a significantly increased risk for manic switches (OR ¼3.54, p¼ .037).…”

“…Two studies by Biederman et al (2009aBiederman et al ( , 2013 reported that subthreshold symptoms of mania in ADHD youth with MDD significantly increased the risk of manic switches. In the first study by Biederman et al (2009a), the investigators reported that subthreshold symptoms of mania were significantly overrepresented in children with ADHD who developed bipolar-I disorder at follow-up compared with those who did not (70% vs 17%, p¼ .002).…”

Alterations in regional homogeneity of resting-state brain activity in patients with major depressive disorder screening positive on the 32-item hypomania checklist (HCL-32)

“…Follow-up studies have shown that the rates of diagnostic change to full-blown BD are significantly higher in HCL-32(+) patients than the rates in HCL-32(-) patients (Biederman et al, 2014;Holma et al, 2008).…”

Special Issues

“…This switching of diagnosis from unipolar depression to BD is up to more than 30 % within a 5-year period, and it is significantly higher in children in comparison to adults (Geller and Luby 1997 ). It is also higher for youths with attention defi cit hyperactivity disorder (ADHD) with subthreshold bipolar features at baseline (57 % vs. 21 %) as well as in those with defi cient emotional self-regulation (Biederman et al 2014 ). ADHD is frequently comorbid with BD and both disorder share many clinical and neurobiological features (Galanter and Leibenluft 2008 ).…”