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The low transcriptionally efficient short-allele of the 5HTTLPR serotonin transporter


has been implicated to moderate the relationship between the experience of

stressful life events (SLEs) and depression. Despite numerous attempts at replicating this

observation, results remain inconclusive.


We examined this relationship in young-adult Non-Hispanic white males and females between

the ages of 22 and 26 (n = 4724) participating in the National Longitudinal Study of Adolescent

to Adult Health (Add Health) with follow-up information every six years since 1995.


Linear and logistic regression models, corrected for multiple testing, indicated that carriers

of one or more of the S-alleles were more sensitive to stress than those with two L-alleles

and at a higher risk for depression. This relationship behaved in a dose-response manner

such that the risk for depression was greatest among those who reported experiencing

higher numbers of SLEs. In post-hoc analyses we were not able to replicate an interaction

effect for suicide ideation but did find suggestive evidence that the effects of SLEs and

5HTTLPR on suicide ideation differed for males and females. There were no effects of childhood



Our results provide partial support for the original hypothesis that 5-HTTLPR genotype interacts

with the experience of stressful life events in the etiology of depression during young

adulthood. However, even with this large sample, and a carefully constructed a priori analysis

plan, the results were still not definitive. For the purposes of replication, characterizing

the 5HTTLPR in other large data sets with extensive environmental and depression measures

is needed.

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