CBCL Pediatric Bipolar Disorder Profile and ADHD: Comorbidity and Quantitative Trait Loci Analysis

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Abstract

Objective

The pediatric bipolar disorder profilme of the Child Behavior Checklist (CBCL-PBD), a parent-completed measure that avoids clinician ideological bias, has proven useful in differentiating patients with attention-deficit/hyperactivity disorder (ADHD). We used CBCL-PBD profiles to distinguish patterns of comorbidity and to search for quantitative trait loci in a genomewide scan in a sample of multiple affected ADHD sibling pairs.

Method

A total of 540 ADHD subjects ages 5 to 18 years were assessed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version and CBCL. Parents were assessed with the Schedule for Affective Disorders and Schizophrenia-Lifetime version supplemented by the Schedule for Affective Disorders and Schizophrenia for School-Age Children for disruptive behavioral disorders. Patterns of psychiatric comorbidity were contrasted based on the CBCL-PBD profile. A quantitative trait loci variance component analysis was used to identify potential genomic regions that may harbor susceptibility genes for the CBCL-PBD quantitative phenotype.

Results

Bipolar spectrum disorders represented less than 2% of the overall sample. The CBCL-PBD classification was associated with increased generalized anxiety disorder (p = .001), oppositional defiant disorder (p = .008), conduct disorder (p = .003), and parental substance abuse (p = .005). A moderately significant linkage signal (multipoint maximum lod score = 2.5) was found on chromosome 2q.

Conclusions

The CBCL-PBD profile distinguishes a subset of ADHD patients with significant comorbidity. Linkage analysis of the CBCL-PBD phenotype suggests certain genomic regions that merit further investigation for genes predisposing to severe psychopathology.

Section snippets

Subjects

Study subjects were 540 children and adolescents ages 5 to 18 years (mean 10.6, SD 3.2) and 519 of their parents ascertained from 270 families with ADHD-affected sibling pairs. Families were included if at least one child met full DSM-IV ADHD criteria and a second child had a diagnosis of definite or probable ADHD, defined as being no more than one symptom short of full criteria, but with evidence of impairment in two settings. All of the families were English speaking. Mean socioeconomic

Results

Subjects' mean (SD) age was 10.6 (3.2) years. Twenty-seven percent of ADHD subjects had increases (T > 70) on the AP subscale, with 31% of these, or 8% of the entire sample, also showing increases on AGG and AD subscales. Sibling scores on the quantitative CBCL-PBD phenotype were highly correlated, with Pearson's r = 0.44 (p < .0001). Of 270 families, 42 (16%) had at least one child meeting CBCL-PBD criteria. The occurrence of bipolar spectrum illness was low in the entire sample, with rates of

Discussion

In a genetically enriched sample of ADHD affected sibling pairs, the CBCL-PBD profile identified a small (8%) but distinct subset of individuals with severe psychopathology. These results are consistent with an earlier report describing similarly increased rates of oppositional defiant, conduct, and anxiety disorders in clinical samples.2 Also in other reports, the CBCL-PBD profile identified increased ADHD, oppositional defiant disorder, conduct disorder, and suicidality in a population-based

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      Previous research has indicated that the CBCL-DP has a different genetic architecture than that of any of its constituent syndromes alone.20 In addition, McGough et al.21 reported different genetic markers associated with the CBCL-DP than with bipolar disorder, depression, or attention problems. What is not clear, however, is whether such genetic findings—or outcome findings—for the DP are specific to elevations on just the 3 constituent syndromes or rather are due to the fact that children in the DP class have high scores on most of the 8 syndromes.

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    This work was supported by National Institute of Mental Health grants MH01969 (to J.J.M.), HD40275 (to S.K.L.), MH01805 (to J.T.M.), MH071852 (to S.F.N.), and MH58277 (to S.L.S.).

    The authors dedicate this article to the memory of Richard D. Todd, M.D., Ph.D. (1951–2008).

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