Candidate gene associations with withdrawn behavior. (28th June 2013)

• Record Type: Journal Article
• Authors: Rubin, David H.; Althoff, Robert R.; Ehli, Erik A.; Davies, Gareth E.; Rettew, David C.; Crehan, Eileen T.; Walkup, John T.; Hudziak, James J.
• Is Part Of: Journal of child psychology and psychiatry and allied disciplines. Volume 54:Number 12(2013:Dec.)
• Page Start: 1337
• Page End: 1345
• Publication Date: 2013-06-28
• Subjects: Child psychology -- Periodicals; Child psychiatry -- Periodicals; 155.4
• DOI: 10.1111/jcpp.12108
• Languages: English
• ISSNs: 0021-9630

Abstract

<abstract abstract-type="main" id="jcpp12108-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="jcpp12108-sec-0001" sec-type="section"> <title>Background</title> <p>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 Withdrawn behavior is highly heritable, persistent, and characteristically worsens without intervention. To date, few studies have successfully identified genetic associations with withdrawn behavior, despite the abundance of evidence of its heritability.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this study is to identify associations between known psychiatric candidate genes and a dimensionally derived measure of withdrawn behavior.</p> </sec> <sec id="jcpp12108-sec-0002" sec-type="section"> <title>Methods</title> <p>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modeling was employed to examine the relationship between genotypes of interest and Child Behavior Checklist (CBCL) Withdrawn Behavior Subscale Score (WBS) while controlling for gender and age through multiple linear regressions.</p> </sec> <sec id="jcpp12108-sec-0003" sec-type="section"> <title>Results</title> <p>Withdrawn behavior was highly associated with polymorphism <ext-link ext-link-type="gen" xlink:href="http://www.ncbi.nlm.nih.gov/nuccore/rs6314?report=GenBank" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">rs6314</ext-link> of the serotonin receptor 2A (<italic>HTR2A</italic>) [<italic>p</italic> = .009, estimate = 0.310 (bootstrap 95% CI 0.155–0.448), bootstrap <italic>p</italic> = .001] and <ext-link ext-link-type="gen" xlink:href="http://www.ncbi.nlm.nih.gov/nuccore/rs1800544?report=GenBank" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">rs1800544</ext-link> of the alpha 2‐adrenergic (<italic>ADRA2A</italic>) [<italic>p</italic> = .001, estimate = −0.310 (bootstrap 95% CI −0.479 to −0.126), bootstrap <italic>p</italic> = .001] genes after correction for gender and age. The association between withdrawn behavior and <italic>ADRA2A</italic> was stronger for younger children.</p> </sec> <sec id="jcpp12108-sec-0004" sec-type="section"> <title>Conclusions</title> <p> <italic>HTR2A</italic> and <italic>ADRA2A</italic> genes are associated with withdrawn behavior. This reinforces the role of catecholaminergic genes in the heritability of withdrawn behavior.</p> </sec> </abstract>