Citation

Rubin DH, Althoff RR, Ehli EA, Davies GE, Rettew DC, Crehan ET, Walkup JT, Hudziak JJ. J. Child Psychol. Psychiatry 2013; 54(12): 1337-1345.

Copyright

(Copyright © 2013, John Wiley and Sons)

DOI

10.1111/jcpp.12108

PMID

unavailable

Abstract

BACKGROUND: Social withdrawal is a core neuropsychiatric phenomenon in developmental psychopathology. Its presence predicts psychopathology across many domains, including depression, psychosis, autism, anxiety, and suicide. Withdrawn behavior is highly heritable, persistent, and characteristically worsens without intervention. To date, few studies have successfully identified genetic associations with withdrawn behavior, despite the abundance of evidence of its heritability. This may be due to reliance of categorical over dimensional measures of the behaviorally inhibited phenotype. The aim of this study is to identify associations between known psychiatric candidate genes and a dimensionally derived measure of withdrawn behavior.

METHODS: Genetic information was collected on 20 single-nucleotide polymorphisms (SNPs) from a custom-designed SNP chip and TAQMAN arrays of 4 variable number of tandem repeat (VNTR) genes for 551 individuals from 187 families. Linear mixed modeling was employed to examine the relationship between genotypes of interest and Child Behavior Checklist (CBCL) Withdrawn Behavior Subscale Score (WBS) while controlling for gender and age through multiple linear regressions.

RESULTS: Withdrawn behavior was highly associated with polymorphism "rs6314" of the serotonin receptor 2A ("HTR2A") [p = 0.009, estimate = 0.310 (bootstrap 95% CI 0.155-0.448), bootstrap p = 0.001] and "rs1800544" of the alpha 2-adrenergic ("ADRA2A") [ p = 0.001, estimate = -0.310 (bootstrap 95% CI -0.479 to -0.126), bootstrap p = 0.001] genes after correction for gender and age. The association between withdrawn behavior and "ADRA2A" was stronger for younger children.

CONCLUSIONS: "HTR2A" and "ADRA2A" genes are associated with withdrawn behavior. This reinforces the role of catecholaminergic genes in the heritability of withdrawn behavior.

Language: en