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
    • "If semi-structured interviews have been used to study irritability and tantrums diagnostically, the Child Behavior Checklist (CBCL;Achenbach, 1991) has been used most frequently to address mood dysregulation dimensionally. Elevated scores on the anxiety/depression, attention/hyperactivity and aggression subscales have been associated with conditions characterized by mood dysregulation (e.g.,Ayer et al., 2009;Holtmann et al., 2007, McGough et al., 2008, Volk & Todd, 2006). T-scores from the aforementioned scales are generally added together with a 180 cut-off for non-clinic samples (Meyer et al., 2009;Kim et al., 2012), which is equivalent to about 1 standard deviation from the mean. "
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    ABSTRACT: Background: This study explores the relationship of irritability to tantrums and loss of temper in a community and clinical sample. Methods: The community sample, recruited via commercial mailing lists, consisted of 462 6-year-olds whose parents completed the Child Behavior Checklist (CBCL), and Preschool Age Psychiatric Assessment (PAPA). Tantrums were assessed in the oppositional defiant disorder (ODD) section of the PAPA. Irritability was assessed in the depression section to identify persistently irritable and/or angry mood. The clinic sample, drawn from a child psychiatry clinic, included 229 consecutively referred 6-year-olds from 2005 through 2014 whose parents completed the CBCL and Child and Adolescent Symptom Inventory (CASI). Temper loss and irritability items came from the ODD and depression sections of the CASI, and tantrum description was taken from an irritability inventory. Children's Global Assessment Scale (CGAS) and the CBCL Dysregulation Profile were examined in both samples. Logistic and multiple regression were used to compare rates of diagnosis, CBCL subscales, CGAS, and tantrum quality between children with tantrums only and tantrums with irritability. Results: Almost half (45.9%) of clinic children had severe tantrums; only 23.8% of those were said to be irritable. In the community, 11% of children had tantrums, but 78.4% of those were called irritable. However, irritability in the clinic, although less common, was associated with aggressive tantrums and substantial impairment. In contrast, irritability was associated with only a relatively small increase in impairment in the community sample. Conclusions: Irritability may have different implications in community versus clinic samples, and tantrums assessed in the community may be qualitatively different from those seen in clinics.
    No preview · Article · Jan 2016 · Journal of child and adolescent psychopharmacology
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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.
    Full-text · Article · Apr 2013 · American Journal of Medical Genetics Part B Neuropsychiatric Genetics
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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.
    Full-text · Article · Jul 2012 · Journal of Attention Disorders
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