Latent Class Analysis Shows Strong Heritability of the Child Behavior Checklist–Juvenile Bipolar Phenotype

Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Biological Psychiatry (Impact Factor: 10.26). 12/2006; 60(9):903-11. DOI: 10.1016/j.biopsych.2006.02.025
Source: PubMed


The Child Behavior Checklist (CBCL) has been used to provide a quantitative description of childhood bipolar disorder (BPAD). Many have reported that children in the clinical range on the Attention Problems (AP), Aggressive Behavior (AGG), and Anxious-Depressed (A/D) syndromes simultaneously are more likely to meet the criteria for childhood BPAD. The purpose of this study was to determine if Latent Class Analysis (LCA) could identify heritable phenotypes representing the CBCL-Juvenile Bipolar (CBCL-JBD) profile and whether this phenotype demonstrates increased frequency of suicidal endorsement.
The CBCL data were received by survey of mothers of twins in two large twin samples, the Netherlands Twin Registry. The setting for the study was the general community twin sample. Participants included 6246 10-year-old Dutch twins from the Netherlands Twin Registry. The main outcome measure consisted of the LCA on the items comprising the AP, AGG, and A/D subscales and means from the suicidal items #18 and #91 within classes.
A 7 class model fit best for girls and an 8 class fit best for boys. The most common class for boys or girls was one with no symptoms. The CBCL-JBD phenotype was the least common--about 4%-5% of the boys and girls. This class was the only one that had significant elevations on the suicidal items of the CBCL. Gender differences were present across latent classes with girls showing no aggression without the CBCL-JBD phenotype and rarely showing attention problems in isolation. Evidence of high heritability of these latent classes was found with odds ratios.
In a general population sample, LCA identifies a CBCL-JBD phenotype latent class that is associated with high rates of suicidality, is highly heritable, and speaks to the comorbidity between attention problems, aggressive behavior, and anxious/depression in children.

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    • "This clinical phenotype appears to be frequently associated with a variety of psychosocial and psychopathological problems, and longitudinal studies suggest that it represents a developmental risk marker of a persistent deficit in the self-regulation of affect and behavior underlying several psychiatric disorders (Holtmann et al., 2011). Twin studies reported relatively high heritability of emotional dysregulation, which ranges from 60% to 80%, depending on the age group of the sample (Althoff et al., 2006; Boomsma et al., 2006; Hudziak et al., 2005; Volk and Todd, 2007). Additive genetic and shared environmental factors represent the major contributions to the variation of this clinical phenotype, with the latter being greater in the youngest children (Boomsma et al., 2006; Hudziak et al., 2005). "
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    ABSTRACT: Background: Two different polymorphisms (TPH2 G-703T and 5-HTTLPR) involved in the serotonergic pathway have been reported to play a role, both alone and in interaction with the environment, in early and adult emotion regulation. As most of these studies are cross-sectional, we know little about the impact of these polymorphisms over time, particularly during adolescence. Methods: Because we were interested in the effects of these polymorphisms and environment (i.e., family structure) at different time-points on the emotional dysregulation profile, we performed a path analysis model in a general adolescent population sample of a five-year follow-up study. Results: We found a high stability of Dysregulation Profile problems independently from the examined allelic variants. We also found that early family structure directly influences the levels of dysregulation problems in early adolescence, both alone and in interaction with TPH2, suggesting the presence of a gene-environment interaction effect. Furthermore, we found that in adolescents homozygous for the TPH2 G allele, the effect of the early family structure remains active during late adolescence, albeit mediated by earlier emotional problems. Limitations: The high attrition rate, the use of only one source on behavioral problems of adolescents, and the focus on a single polymorphism in the investigated genes could limit the generalizability of the present results. Conclusions: These results suggest that early family structure could play a significant role in the development and maintenance of emotional and behavioral problems not only in early adolescence but also in late-adolescence, although this effect was mediated and moderated by behavioral and genetic variables.
    Journal of Affective Disorders 11/2015; 190. DOI:10.1016/j.jad.2015.10.057 · 3.38 Impact Factor
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    • "Hudziak et al (2005) estimated that in their sample of Dutch twins, the prevalence of this phenotype occurs in approximately 1% of children of all ages sampled (7, 10 & 12 years). When a Latent class analysis (LCA) approach was used, 4% of girls and 5% of boys were found to be consistent with this phenotype (Althoff et al., 2006). This research group has also shown stability of the phenotype across time (Boomsma et al., 2006), with genetic factors accounting for the majority of the variance in stability (Boomsma et al., 2006). "
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    ABSTRACT: To assess the late adolescent psychiatric outcomes associated with a positive Child Behavior Checklist-Juvenile Bipolar Disorder Phenotype (CBCL-JBD) in children diagnosed with ADHD and followed over a 9-year period. Parents of 152 children diagnosed as ADHD (ages 7-11 years) completed the CBCL. Ninety of these parents completed it again 9 years later as part of a comprehensive evaluation of Axis I and II diagnoses as assessed using semi-structured interviews. As previously proposed, the CBCL-JBD phenotype was defined as T-scores of 70 or greater on the Attention Problems, Aggression, and Anxiety/Depression subscales. The CBCL-JBD phenotype was found in 31% of those followed but only 4.9% of the sample continued to meet the phenotype criteria at follow-up. Only two of the sample developed Bipolar Disorder by late adolescence and only one of those had the CBCL-JBD profile in childhood. The proxy did not predict any Axis I disorders. However, the CBCL-JBD proxy was highly predictive of later personality disorders. Only a subgroup of the original childhood sample was followed. Given this sample was confined to children with ADHD, it is not known whether the prediction of personality disorders from CBCL scores would generalize to a wider community or clinical population. A positive CBCL-JBD phenotype profile in childhood does not predict Axis I Disorders in late adolescence; however, it may be prognostic of the emergence of personality disorders.
    Journal of Affective Disorders 11/2010; 130(1-2):155-61. DOI:10.1016/j.jad.2010.10.019 · 3.38 Impact Factor
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    • "LCA is a statistical procedure that allows the investigator to test empirically for the existence of discrete groups who endorse similar patterns of symptoms (Hudziak et al., 1998). In a general population Dutch twin sample, we have conducted LCA on maternal reports of the attention problems, aggressive behavior, and anxious/depressed subscales of the CBCL (Althoff et al., 2006). A class that approximated the Dysregulation Profile was the least common -about 4–5% of the boys and girls by maternal report. "
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    ABSTRACT: The Dysregulation Profile (DP) of the Child Behavior Checklist (CBCL) (previously called the CBCL-Juvenile Bipolar Disorder or CBCL-JBD profile) characterized by elevated scores on CBCL attention problems, aggressive behavior, and anxious/depressed scales is associated with severe psychopathology and suicidal behavior. The stability of this profile across informants has not been established. In this study, agreement across parent, teacher, and self-reports was examined for the Dysregulation Profile phenotype derived using latent class analysis of a national probability sample of 2031 children aged 6-18. The Dysregulation Profile latent class was found for each informant and accounted for 6-7% of the sample. There was mild to fair agreement on the Dysregulation Profile latent class between parents and youth (Kappa=0.22-0.25), parents and teachers (Kappa=0.14-0.24) and youth and teachers (Kappa=0.19-0.28). When parents and youth reports both placed children into the Dysregulation Profile latent class, 42% of boys and 67% of girls reported suicidal thoughts or behavior. We conclude that the Dysregulation Profile latent class is identified across informants although agreement of specific individuals is mild. Children in this class as identified by parental and youth reports have a very high risk for suicidal thoughts and behaviors.
    Psychiatry Research 08/2010; 178(3):550-5. DOI:10.1016/j.psychres.2010.05.002 · 2.47 Impact Factor
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