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Serotonin transporter polymorphism (5HTTLPR), severe childhood abuse and depressive symptom trajectories in adulthood

Abstract

Background Cross-sectional studies suggest that the serotonin transporter promoter region polymorphism (5-HTT gene-linked polymorphic region, 5HTTLPR) moderates the relationship between childhood abuse and major depressive disorder.

Aims To examine whether the 5HTTLPR polymorphism moderates the effect childhood abuse has on 5-year depressive symptom severity trajectories in adulthood.

Method At 5-year follow-up, DNA from 333 adult primary care attendees was obtained and genotyped for the 5HTTLPR polymorphism. Linear mixed models were used to test for a genotype × childhood abuse interaction effect on 5-year depressive symptom severity trajectories.

Results After covariate adjustment, homozygous s allele carriers with a history of severe childhood abuse had significantly greater depressive symptom severity at baseline compared with those without a history of severe childhood abuse and this effect persisted throughout the 5-year period of observation.

Conclusions The 5HTTLPR s/s genotype robustly moderates the effects of severe childhood abuse on depressive symptom severity trajectories in adulthood.

Declaration of interest None.

Copyright and usage © The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

Exposure to adverse life events during childhood has consistently been linked to increased risk of depression in adulthood.^1,2 However, early life exposure to adversity alone is likely not sufficient to elicit depression later in life. In fact, evidence to date suggests that some individuals are more susceptible to negative outcomes following exposure to adversity and that this susceptibility in part may reside in an individual's genome.

Over the past decade, genetic variation in over 35 genes have been examined for their interaction with adverse life events.³ Among these genes, the serotonin transporter (SLC6A4) and its corresponding length polymorphisms located in the 5′-flanking promoter region (5-HTT gene-linked polymorphic region, 5HTTLPR)⁴ is arguably the most studied in relation to depression and exposure to adverse life events, namely severe childhood abuse. The initial study conducted by Caspi et al⁵ reported that young adults with the s allele were more likely to develop depression after exposure to severe childhood abuse compared with those with the l allele and proposed that the s allele may be a moderator (effect modifier) of the relationship between stress and depression. However, meta-analyses have both supported⁶ and rejected this notion⁷ and researchers have since criticised the reliance on cross-sectional designs, inadequate adjustment for potential confounders and clinical utility of the gene × environment studies conducted to date.^8,9

In response to these criticisms, the present study examined the interaction between the 5HTTLPR polymorphism and history of severe childhood abuse on depressive symptom trajectories in a 5-year prospective cohort of primary care attendees. Linear mixed modelling was used to test whether 5HTTLPR genotype moderated the effect of severe childhood abuse on depressive symptom trajectories. We hypothesised that s/s carriers would be more likely to experience severe depressive symptom trajectories following exposure to severe childhood abuse compared with s/l or l/l.