Abstract 1390: Tryptophan Hydroxylase Gene Haplotypes Modify the Effect of Childhood Emotional Abuse on Symptoms of Depression
Background Tryptophan hydroxylases (TPH) are involved in the biosynthesis of serotonin and are therefore candidate genes for depression, an independent risk factor for cardiovascular disease. Childhood trauma is also an important contributor to depression and is likely to moderate the effect of TPH polymorphisms on the susceptibility to depression. No previous study has examined the interactions between TPH1 and TPH2 haplotypes and childhood trauma on vulnerability to depressive symptoms.
Hypothesis TPH polymorphisms are implicated in depressive symptoms, and childhood trauma moderates the association between TPH haplotypes and depressive symptoms.
Methods We conducted gene-based haplotype analyses using 17 tag SNPs across the TPH1 and TPH2 genes to test main haplotypic effects and haplotype x childhood trauma interactions on depressive symptoms, controlling for known risk factors. A twin sample including 169 middle-aged male twin pairs drawn from the Vietnam Era Twin Registry was used. Depressive symptoms were assessed by Beck Depressive Inventory-II. Childhood trauma, before age 18, was measured with the Early Trauma Inventory and included physical, emotional and sexual abuse and general trauma. Generalized estimating equation was used to account for within-pair correlations.
Results No main haplotypic effects were found. However, childhood emotional abuse significantly moderated the effects of three TPH haplotypes, one in the TPH1 gene (Hap-T1) and two in the TPH2 gene (Hap-T2 and Hap-T3), on vulnerability to depressive symptoms. In the absence of emotional abuse, haplotype carrier status was not associated with depressive symptoms. However, in the presence of emotional abuse, carriers for Hap-T1 and Hap-T2 exhibited significant higher depressive scores (both p=0.03), whereas carriers of Hap-T3 had significant lower depressive scores than noncarriers of these haplotypes (p=0.01), demonstrating the dependency of TPH haplotypes on emotional abuse in leading to susceptibility for depressive symptoms.
Conclusions This study demonstrates, for the first time, that childhood emotional abuse significantly modulates the association between TPH haplotypes and depressive symptoms, independent of traditional risk factors.
This research has received full or partial funding support from the American Heart Association, National Center.