Sibling-based association analyses of the serotonin transporter polymorphism and internalizing behavior problems in children.
BACKGROUND
Childhood internalizing problems are often precursors in the development of more serious psychiatric syndromes including anxiety and depressive disorders. Twin studies of the etiology of these disorders suggest that the genetic risk factors underlying anxiety and depression are highly correlated. However, the specific genetic mechanisms responsible for this risk have not yet been identified.


METHODS
We examined the association between childhood internalizing problems and a functional polymorphism in the serotonin transporter gene (5-HTTLPR) in 711 children participating in a longitudinal twin study of behavioral and emotional development. Internalizing problems were measured at ages 4, 7, 9, 10, 11 and 12 years using the Child Behavior Checklist (CBCL) parent report form. We applied a sibling-based methodology for estimating allelic association with quantitative traits, while controlling for population stratification.


RESULTS
No associations were found for CBCL Internalizing problems at any age, including the subscales for Somatic Complaints, Withdrawn and Anxiety/Depression.


CONCLUSIONS
Thus, although our results did not support the hypothesis that the 5-HTTLPR contributes to a dimensional expression of internalizing behavior problems, this does not rule out the possibility that it is an interesting polymorphism to pursue in the search for genetic risk factors related to major depressive and/or anxiety disorders.
Young
Susan E
SE
Institute for Behavioral Genetics, University of Colorado, Boulder 80309, USA. Susan.Young@Colorado.edu
Smolen
Andrew
A
Stallings
Michael C
MC
Corley
Robin P
RP
Hewitt
John K
JK
D001008:Anxiety Disorders / Q000235:genetics* / Q000503:physiopathology*; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003866:Depressive Disorder / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins