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Genetics of callous-unemotional behavior in children.

ABSTRACT: Callous-unemotional behavior (CU) is currently under consideration as a subtyping index for conduct disorder diagnosis. Twin studies routinely estimate the heritability of CU as greater than 50%. It is now possible to estimate genetic influence using DNA alone from samples of unrelated individuals, not relying on the assumptions of the twin method. Here we use this new DNA method (implemented in a software package called Genome-wide Complex Trait Analysis, GCTA) for the first time to estimate genetic influence on CU. We also report the first genome-wide association (GWA) study of CU as a quantitative trait. We compare these DNA results to those from twin analyses using the same measure and the same community sample of 2,930 children rated by their teachers at ages 7, 9 and 12. GCTA estimates of heritability were near zero, even though twin analysis of CU in this sample confirmed the high heritability of CU reported in the literature, and even though GCTA estimates of heritability were substantial for cognitive and anthropological traits in this sample. No significant associations were found in GWA analysis, which, like GCTA, only detects additive effects of common DNA variants. The phrase 'missing heritability' was coined to refer to the gap between variance associated with DNA variants identified in GWA studies versus twin study heritability. However, GCTA heritability, not twin study heritability, is the ceiling for GWA studies because both GCTA and GWA are limited to the overall additive effects of common DNA variants, whereas twin studies are not. This GCTA ceiling is very low for CU in our study, despite its high twin study heritability estimate. The gap between GCTA and twin study heritabilities will make it challenging to identify genes responsible for the heritability of CU.

SUBMITTER: Viding E

PROVIDER: S-EPMC3706442 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Genetics of callous-unemotional behavior in children.

Viding Essi E Price Thomas S TS Jaffee Sara R SR Trzaskowski Maciej M Davis Oliver S P OS Meaburn Emma L EL Haworth Claire M A CM Plomin Robert R

PloS one 20130709 7

Callous-unemotional behavior (CU) is currently under consideration as a subtyping index for conduct disorder diagnosis. Twin studies routinely estimate the heritability of CU as greater than 50%. It is now possible to estimate genetic influence using DNA alone from samples of unrelated individuals, not relying on the assumptions of the twin method. Here we use this new DNA method (implemented in a software package called Genome-wide Complex Trait Analysis, GCTA) for the first time to estimate ge ...[more]

PMID: 23874384

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Project description:ObjectiveDisrupted reward processing is implicated in the etiology of disruptive behavior disorders (DBDs) and callous-unemotional traits. However, neuroimaging investigations of reward processing underlying these phenotypes remain sparse. The authors examined neural sensitivity in response to reward anticipation and receipt among youths with DBDs, with and without callous-unemotional traits.MethodsData were obtained from the Adolescent Brain and Cognitive Development Study (mean age=9.51 years [SD=0.50]; 49% female). Reward-related activation during the monetary incentive delay task was examined across 16 brain regions, including the amygdala, anterior cingulate cortex (ACC), nucleus accumbens (NAcc), and orbitofrontal cortex (OFC). Latent variable modeling was used to examine network-level coactivation. The following diagnostic groups were compared: typically developing youths (N=693) and youths with DBDs (N=995), subdivided into those with callous-unemotional traits (DBD+CU, N=198) and without callous-unemotional traits (DBD only, N=276).ResultsDuring reward anticipation, youths in the overall DBD group (with and without callous-unemotional traits) showed decreased dorsal ACC activation compared with typically developing youths. The DBD-only group exhibited reduced ventral and dorsal striatal activity compared with the DBD+CU and typically developing groups. During reward receipt, youths with DBDs showed increased cortical (e.g., OFC) and subcortical (e.g., NAcc) regional activation compared with typically developing youths. The DBD+CU group demonstrated greater activation in several regions compared with those in the typically developing (e.g., amygdala) and DBD-only (e.g., dorsal ACC) groups. At the network level, the DBD-only group showed reduced anticipatory reward activation compared with the typically developing and DBD+CU groups, whereas youths in the DBD+CU group showed increased activation during reward receipt compared with those in the typically developing group.ConclusionsThese findings advance our understanding of unique neuroetiologic pathways to DBDs and callous-unemotional traits.

Project description:Callous-unemotional (CU) traits are characterized by a lack of responsiveness to the emotions of others, particularly negative emotions. A parenting environment where the child's own distress emotions are sensitively responded to may help foster the child's ability to respond to the emotions of others. We tested whether maternal sensitivity to distress, and other parenting characteristics, were associated with CU traits over the preschool period, and examined whether this was mediated via infant attachment status.In an epidemiological cohort, CU traits were assessed at age 2.5, 3.5, and 5.0 years by mother report. Dimensions of parenting were assessed in free play at age 29 weeks in a stratified subsample of 272, and attachment status at 14 months (n = 265). Structural equation modelling with maximum likelihood estimation was used to examine predictions from parenting dimensions and attachment status.A parenting factor comprised of sensitivity to distress (n = 207), sensitivity to non-distress, positive regard toward the infant (or warmth), and intrusiveness, predicted child CU traits (p = .023). This effect was accounted for mainly by sensitivity to distress (p = .008) and positive regard (p = .023) which showed a synergistic effect as evidenced by a significant interaction (p = .01). This arose because the combination of low sensitivity to distress and low positive regard created the risk for elevated CU traits. Although sensitivity and positive regard predicted attachment security and disorganization, there were no associations between attachment status and CU traits.The finding of contributions from both sensitivity to distress and positive regard to reduced CU traits suggests that children's responsiveness to others' emotions may be increased by their own mothers' responsiveness to them and their mothers' warmth. There was no evidence that this was mediated via attachment status. Implications for intervention and future directions are discussed.

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Genetics of callous-unemotional behavior in children.

Publications

Genetics of callous-unemotional behavior in children.

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