This study evaluated the prognostic utility of the CBCL-PBD profile as a predictor of a subsequent diagnosis of bipolar disorder in children with ADHD. Consistent with our study hypothesis, we found that a positive CBCL-PBD score predicted a subsequent diagnosis of bipolar disorder and syndrome congruent outcomes including major depression and conduct disorder as well as impaired psychosocial functioning and a higher risk for psychiatric hospitalization. These longitudinal results support the utility of the CBCL-PBD score to predict a diagnosis of bipolar disorder and syndrome congruent associated impairments in ADHD youth.
The finding that the CBCL-PBD profile has predictive value provides further support for the utility of this profile to help identify children at high risk for bipolar disorder. This profile has been previously shown to have high diagnostic efficiency to predict a current diagnoses of bipolar disorder,17
and has been replicated across multiple age groups, multiple treatment settings, and multiple cultures.21–24,46,47
The CBCL-PBD score also predicted subsequent major depression, conduct disorder, poor psychosocial outcomes, and psychiatric hospitalization, all of which are syndromatic features consistent with a diagnosis of pediatric bipolar disorder. For example, major depression is a syndrome congruent expression of bipolar disorder.31,48,49
Likewise, the finding that the CBCL-PBD score predicted subsequent diagnoses of conduct disorder is also congruent with the diagnosis of pediatric BPD. A high and bidirectional overlap between pediatric bipolar disorder and conduct disorder has been documented in studies of both children with bipolar disorder and children with conduct disorder.32,50
Also syndrome congruent with the diagnosis of pediatric bipolar disorder is the finding that the CBCL-PBD score was predictive of compromised psychosocial outcomes and psychiatric hospitalization, adverse outcomes previously documented in studies of youth with bipolar disorder.33,51,52
Psychiatric hospitalization was the strongest association found in our analysis, and because 90% of the hospitalizations involved mood disorders, the CBCL-PBD score may be particularly suited for identifying those children at risk for developing severely impairing mood disorders.
Although Volk et al.27
failed to find a cross-sectional association between the CBCL-PBD profile and structured interview based diagnoses of pediatric BPD using data from a population-based pediatric twin sample, children with a positive CBCL-PBD subjects had more oppositional defiant disorder (ODD), conduct disorder (CD), and attention deficit hyperactivity disorder (ADHD) and more frequently endorsed suicidal behaviors. This is consistent with our finding that ADHD subjects with a CBCL-PBD Positive score had higher rates of ODD and CD at baseline, which is also well documented by prior studies.53,54
Volk et al.27
may not have found a significant association between the CBCL-PBD profile and pediatric BPD due to the low rate of bipolar disorder in their sample. The CBCL-PBD profile in Volk et al.27
study was heritable and associated with the number of dopamine transporter (DAT1) 9-repeat 3’ untranslated region alleles, a region recently associated with pediatric bipolar disorder.
Two other studies did not find a cross-sectional association between the CBCL-BPD profile and bipolar disorder. In the negative study by McGough et al.55
the CBCL-PBD phenotype was associated with generalized anxiety disorder, ODD, and CD. The negative study by Youngstrom et al.26
used data from a large sample derived from six urban community mental health centers (N=3086). Their negative findings could have been due to their reliance on archival data and limited emphasis on operationalized diagnostic algorithms. In addition, Youngstrom et al.’s sample was 42% African American, whereas 99% of our sample was Caucasian, which may have accounted for some of the differences between the studies. More work is needed to help reconcile these discrepant findings.
Although there is some disagreement among the cross-sectional studies, our study and the only other longitudinal study available both find that the CBCL-PBD phenotype predicts subsequent bipolar disorder and other adverse outcomes. Meyer et al.28
found that in childhood and adolescence the CBCL-PBD phenotype was associated with anxiety disorders, disruptive behavior disorders, MDD/dysthymia, suicidal ideation, and suicidal attempt.28
It was not until the young adult follow-up (average age=21.7 years) that the CBCL-PBD phenotype was found to predict bipolar disorder.28
Taken together with our findings, these results suggest that even in the absence of a current diagnosis of pediatric BPD, a positive CBCL-PBD profile may be indicative of a future risk for bipolar disorder in children with a positive profile.
Because the majority of subjects who had a positive CBCL-PBD score did not develop bipolar disorder, and a positive CBCL-PBD score was also associated with subsequent MDD and CD, some may question the naming of this “bipolar disorder” profile. We use the name CBCL-PBD to be consistent with the previous literature16,27,28,55–58
and due to the current findings that a positive CBCL-PBD score is a significant risk factor for bipolar disorder. However, we emphasize that while the CBCL-PBD profile could be useful to help identify children at risk for BPD, clinicians should not use the CBCL to make a diagnosis of bipolar disorder. Clearly, the diagnosis of pediatric bipolar disorder is a complicated and non-trivial enterprise. It involves careful examination of the child and parental reporting of the child’s history, as well as information on family history and life charting to help clarify a diagnosis. Unfortunately, there continues to be debate in the field about the best diagnostic definition of pediatric bipolar disorder,7
which is influenced by clinical traditions, interview methods and differing interpretations of the nature of a mood episode. We expect that advances in the field and the refinements to come with DSM-V will improve the diagnostic process. However, for clinicians who are not skilled in diagnosing bipolar disorder, the CBCL-PBD can identify children who should be referred to an expert diagnostician. At a very minimum, the CBCL-PBD score could alert the clinician that the child is at risk for serious adverse psychopathological outcomes.
Our findings should be evaluated in light of some methodological limitations. We examined only the CBCL-PBD profile as a predictor of subsequent bipolar disorder. Other screening instruments have effectively discriminated pediatric bipolar disorder cases from non-cases59,60
, and future studies should examine their longitudinal utility. The CBCL remains an attractive tool for identifying children at risk for bipolar disorder due to its ease of administration, brevity, and reliability.20
In clinical practice it may be useful to probe some items of the CBCL and re-score them according to clinical judgment. However, our CBCL scores were based solely on the mother’s scoring, thereby using a standardized assessment procedure that ensures rigorous comparison to other studies using the same research methods.20
This raises the possibility of additional variability between sites that do and do not re-score CBCL items. Because the sample consisted of youth with ADHD, uncertainties remain as to whether our finding will generalize outside the context of ADHD. Since subjects were referred, the findings may not generalize to community samples. Since subjects were Caucasians, findings may not generalize to other ethnic groups. Children younger than 12 years of age were not directly interviewed, which may have led to underestimates of psychopathology, especially for internalizing disorders. Although raters administering the structured diagnostic interviews were highly selected, trained and supervised, they were not clinicians. Although our assessment methods may not elicit the same quality of information as of clinician interviews, in prior work we have shown 90 percent agreement between expert clinician-derived diagnoses of pediatric bipolar disorder and the structured interview diagnoses of non-clinical raters.61
Differing diagnostic cultures could account for the different findings of studies at various institutions.
Despite these limitations, this work suggests that the CBCL-PBD score based on the elevations on the Attention Problems, Aggressive Behavior, and Anxious/Depressed subscales is predictive of pediatric bipolar disorder and associated impairments. If confirmed in other studies, the CBCL-PBD score has the potential to be a useful screening instrument to help identify children at high risk to develop bipolar disorder.