Of 280 probands with ADHD and their 74 siblings with ADHD at baseline, 161 had a lifetime history of a major depressive episode. Of these 161 subjects, 36 were dropped because they also had a history of BP-I disorder at baseline. Of the remaining 125 subjects, 115 had follow-up data (95 probands, 20 siblings). Of 242 Control probands and their 236 siblings without ADHD at baseline, 58 had a lifetime history of a major depressive episode. Of these 58 subjects, 2 were dropped because they also had a history of BP-I disorder at baseline. Of the remaining 56 subjects, 53 had follow-up data (23 probands, 30 siblings). This yielded a total sample of 168 subjects who had a lifetime history of unipolar MDD at baseline (53 Controls, 115 ADHD). The average time from the baseline to the last assessment was 7.1 years (standard deviation=3.2 years).
Of the pool of 181 subjects at baseline with MDD and without BP-I disorder, a higher percentage of subjects from the boys’ study had follow-up data (79/81, 98%) compared to the girls study (89/100, 89%, p=0.05). Subjects assessed at follow-up (N=168) were slightly older at baseline (mean=13.2 years, SD=3.6) than subjects lost to follow-up (N=13, mean=11.0 years, SD=2.8, p=0.02). There were no differences between subjects assessed at follow-up and lost to follow-up on gender (p=0.18), socioeconomic status (SES, p=0.70), or ascertainment source (p=0.41).
Is ADHD a risk factor for Switching from Unipolar Depression to Mania?
As shown in , analysis of data from subjects with unipolar MDD without full or subthreshold BP-I at baseline (N=105 ADHD, N=50 Controls), showed that a significantly higher number of ADHD subjects with unipolar MDD switched to bipolar disorder at follow-up than did Controls with unipolar MDD (ADHD=27.6% [17.1% BP-I, 10.5% subthreshold BP-I] versus Controls=6.0% [4.0% BP-I, 2.0% subthreshold BP-I], z=2.80, p=0.005).
Rates of bipolar spectrum disorders at follow-up in subjects with MDD at baseline.
Baseline Predictors of Switching from Unipolar Depression to Mania
In ADHD subjects, subthreshold BP-I disorder at baseline significantly increased the risk for the development of a full BP-I disorder at follow up (70% vs 17%, z=3.17, p=0.002). In contrast all 3 (6%) of Controls with unipolar MDD and subthreshold bipolar disorder at baseline remitted at follow-up. Six of the subjects with ADHD and subthreshold bipolar disorder at baseline who developed full BP-I at follow-up had symptom data available at baseline. Among these, the symptom prevalences were Distractibility (100%), Flight of Ideas/Racing Thoughts (83%), Decreased Need for Sleep (67%), Irritable Mood (50%), Increased Energy and Poor Judgment (33% each), and Elated Mood, Grandiosity, and Accelerated Speech (17% each).
Comparison of baseline findings between ADHD subjects with unipolar MDD who did (N=29) and did not (N=76) switch to full or subthreshold BP-I disorder showed that the two groups did not significantly differ on age at last assessment, gender distribution, socioeconomic status, ascertainment source (pediatric versus psychiatric), or study of ascertainment (boys or girls study) (). However, subjects who switched from unipolar MDD to bipolar disorder were slightly younger at baseline and more likely to be male compared to subjects who did not switch. Therefore, baseline age and gender were statistically controlled for in all comparisons.
Demographic features of subjects with MDD who did and did not switch to bipolar disorder at follow-up.
There were no significant differences at baseline between subjects who did and did not switch to bipolar disorder on age at onset of MDD (7.4 ± 4.4 years versus 8.0 ± 4.4, respectively, t=1.62, p=0.11), duration of MDD (3.2 ± 3.8 versus 2.4 ± 2.9 years, respectively, t=−1.78, p=0.08), MDD associated impairment (55% versus 39% severely impaired, respectively, z=−0.63, p=0.53), use of pharmacotherapy for MDD (38% versus 30%, respectively, z=0.26, p=0.79), or need for hospitalization for MDD (3% versus 4%, respectively, z=−0.73, p=0.47). There were no meaningful differences between the groups in individual symptoms of MDD either.
In contrast, subjects who switched to bipolar disorder at follow were significantly more likely to have comorbid conduct disorder at baseline compared to subjects who did not switch (34% versus 14%, z=2.64, p=0.008) and were significantly more likely to have more “School behavior problems” compared to subjects who did not switch (83% versus 59%, z=2.27, p=0.02). In addition, subjects who switched from unipolar MDD to bipolar disorder had a significantly higher rate of parental mood disorders compared to subjects who did not switch (68% versus 35%, ). Although failing to reach our threshold for statistical significance, subjects who switched to bipolar disorder had twice the rates of parental MDD (60% versus 32%) and parental BPD (20% versus 11%).
Parental psychopathology in subjects who did and did not switch to BPD.
shows the additive risk of the significant predictors found above. Only 5% (1/20) of subjects with no risk factors switched to bipolar disorder, while 24% (11/46) of subjects with one risk factor (z=1.98, p=0.047 versus no risk factors) and 32% (9/28) of subjects with two risk factors (z=2.12, p=0.03 versus no risk factors) switched. Subjects with all three risk factors had a significantly increased risk; 73% (8/11) of these subjects switched to bipolar disorder (z=3.76, p<0.001 versus no risk factors; z=2.96, p=0.003 versus 1 risk factor; z=2.73, p=0.006 versus 2 risk factors).
Additive risk of multiple risk factors for switching to bipolar disorder (conduct disorder, school behavior problems, parental mood disorder) in ADHD subjects with MDD.
shows rates of BPD symptoms at follow-up in subjects who switched to full and subthreshold BP-I disorder. These rates were compared to those reported by Kowatch et al. (2005) in a meta-analysis of pediatric bipolar disorder (). Over 80% of subjects who switched to full BP-I disorder had pressured speech, racing thoughts, distractibility, poor judgment, and increased activity, followed by over 70% with elated mood, irritable mood, and decreased sleep, and finally grandiosity (62%). Over 80% of subjects who switched to subthreshold BP-I disorder had distractibility, poor judgment, and increased activity, followed by over 40% with irritable mood, grandiosity, decreased sleep, and racing thoughts, and finally elated mood (18%) and pressured speech (36%).
BPD symptoms at follow-up in subjects who switched to BPD.