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

Division of Child and Adolescent Psychiatry, UCLA Semel Institute for Neuroscience and Human Behavior and David Geffen School of Medicine,
Journal of the American Academy of Child and Adolescent Psychiatry (Impact Factor: 7.26). 09/2008; 47(10):1151-7. DOI: 10.1097/CHI.0b013e3181825a68
Source: PubMed


The pediatric bipolar disorder profile 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.
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.
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.
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.

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Available from: Shaunna L Clark, Jan 05, 2014
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    • "The disorder has predominantly been studied in children, but at least one-third of patients continue to have impairing symptoms into adulthood [Faraone, 2006]. The clinical presentation of ADHD in adults typically includes comorbidity with other psychiatric disorders [Kessler et al., 2006; Sobanski et al., 2007; McGough et al., 2008; Haavik et al., 2010]. We have recently shown that 12% of our clinically diagnosed adult ADHD patients report a lifetime history of BPD and that 51% of the ADHD patients screened positive for a bipolar spectrum disorder, as defined by the Mood Disorder Questionnaire (MDQ), compared to 1.7% and 8.3% of population derived controls, respectively [Halmøy et al., 2010]. "
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    ABSTRACT: The DISC1 gene was named after its discovery in a Scottish pedigree with schizophrenia (SCZ) patients. However, subsequent studies have shown association of DISC1 variants with a range of different neurocognitive phenotypes and psychiatric disorders, including bipolar disorder (BPD), and major depression. Attention-deficit/hyperactivity disorder (ADHD) shares some symptoms with BPD and ADHD patients often suffer from comorbid affective disorders. We wanted to examine the role of DISC1 in ADHD, and with comorbid symptoms of mood disorders. Eleven single nucleotide polymorphisms (SNPs) previously implicated in SCZ and BPD, and a DISC1 duplication involving exon 1, were genotyped in 561 adult ADHD cases and 713 controls of Norwegian ancestry. The intronic SNP rs1538979 was associated with ADHD in the Norwegian sample [odds ratio (OR): 1.33, 95% confidence interval (CI) 1.03-1.73, P = 0.03] and replicated in a Spanish adult ADHD sample of 694 cases and 735 controls, using the tagging SNP rs11122330 (meta-analysis: P = 0.008, OR 1.25, 95% CI 1.06-1.47). In the Norwegian ADHD sample we also observed an association between the Phe607-variant of rs6675281 and a positive score on the Mood Disorder Questionnaire (MDQ; OR = 1.44, 95% CI 1.08-1.93, P = 0.01). To our knowledge, this is the first study to show an association between DISC1 variants and ADHD. Our study suggests that further studies are warranted to resolve if DISC1 variation is involved in several common neurodevelopmental disorders including ADHD. © 2013 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 04/2013; 162(3). DOI:10.1002/ajmg.b.32136 · 3.42 Impact Factor
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    • "As ADHD is increasingly viewed as a disorder of cognitive , behavioral, and emotional dysregulation (Barkley, 1997), CBCL-DP may be a useful complementary assessment to identify ADHD children with specific clinical or cognitive characteristics, potentially associated with poorer outcomes and specific therapeutic needs. In ADHD children , CBCL-DP has been associated with higher rates of comorbid oppositional defiant disorders, conduct disorders , and generalized anxiety disorders (McGough et al., 2008). The efficacy and safety of pharmacological interventions in this subgroup of ADHD children have not been sufficiently investigated. "
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    ABSTRACT: Objective: The Child Behavior Checklist-Dysregulation Profile (CBCL-DP), characterized by elevated scores on the "Attention Problems," "Aggressive Behavior," and "Anxious/Depressed" scales in the CBCL, has been associated with later severe psychopathology. In a sample of children with ADHD, this study sought to further explore the clinical characteristics, the response to methylphenidate medication, and the cognitive features of ADHD children with CBCL-DP. Method: The sample consisted of 173 ADHD outpatients (age = 10.9 ± 2.81) assessed using symptom severity scales, personality questionnaires (Emotionality Activity Sociability [EAS] and Junior Temperament and Character Inventory [JTCI]), and neuropsychological tests. A subsample of 136 participants was reassessed after optimal adjustment of methylphenidate dosage. Results and conclusion: Variables that were independently associated with CBCL-DP were clinical severity (ADHD Rating Scale [ADHD-RS]), internalized disorders, high emotionality (EAS), and low self-directedness (JTCI). CBCL-DP was associated neither with poorer response to methylphenidate nor with more side effects. There were no differences in cognitive performances between participants with and without CBCL-DP.
    Journal of Attention Disorders 07/2012; 19(1). DOI:10.1177/1087054712452135 · 3.78 Impact Factor
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    • "Consistent with our hypotheses, multivariate analyses revealed that preschoolers with the CBCL-DP were distinguished by depressive and ODD symptoms, impaired functioning, high temperamental negative affectivity and low effortful control, maternal authoritarian parenting, and paternal permissive parenting. These findings are consistent with studies of community (Althoff et al., 2010; Holtmann et al., 2011; Volk & Todd, 2007) and clinical (Diler et al., 2009; McGough et al., 2008; Youngstrom et al., 2005) samples of older youth reporting that the CBCL-DP is associated with high levels of internalizing symptoms, externalizing symptoms, and functional impairment. Thus, even as early as the pre-school period, the CBCL-DP identifies children with a range of emotional and behavioral problems and impaired functioning. "
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    ABSTRACT: A growing literature indicates that the Child Behavior Checklist-Dysregulation Profile (CBCL-DP) identifies youths with heightened risk for severe psychopathology, comorbidity, and impairment. However, this work has focused on school-age children and adolescents; no studies have examined whether preschool-aged children with the CBCL-DP exhibit a similar constellation of problems. Using a community sample of preschoolers, we compared children with (N = 61) and without (N = 488) the CBCL-DP on a broad range of variables assessed using multiple methods. Univariate analyses revealed numerous differences between children with the CBCL-DP and their peers on psychiatric symptomatology, temperament, parenting behavior, and parental personality, psychopathology, and marital functioning. In multivariate analyses, children with the CBCL-DP exhibited greater temperamental negative affectivity and lower effortful control. They also had more depressive and oppositional defiant symptoms, as well as greater functional impairment. Parents of CBCL-DP children reported engaging in more punitive, controlling parenting behavior than parents of non-profile children. In a non-clinical sample of preschoolers, the CBCL-DP is associated with extensive emotional and behavioral dysregulation and maladaptive parenting.
    Journal of Child Psychology and Psychiatry 03/2012; 53(9):918-26. DOI:10.1111/j.1469-7610.2012.02546.x · 6.46 Impact Factor
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