Social Adversity, the Serotonin Transporter (5-HTTLPR) Polymorphism and Major Depressive Disorder

Strangeways Research Laboratory and University of Cambridge Department of Public Health and Primary Care, Worts Causeway, Cambridge, UK.
Biological Psychiatry (Impact Factor: 10.26). 03/2006; 59(3):224-9. DOI: 10.1016/j.biopsych.2005.07.014
Source: PubMed


Recent evidence has suggested that the short allele of the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR of the human serotonin gene [SLC6A4]) is associated with increased risk of depressive disorder but only among individuals exposed to social adversity. We report an investigation designed to replicate this finding.
Data were available from a non-clinical sample of 4,175 adult men and women, ages 41-80 years, selected from participants in the European Prospective Investigation into Cancer and Nutrition in Norfolk (EPIC-Norfolk, United Kingdom) study. Evidence of past-year prevalent episodic major depressive disorder (MDD), defined by restricted DSM-IV diagnostic criteria, was assessed through questionnaire. Adverse experiences in childhood and in adulthood (during the five years preceding assessment) were also assessed through self-report. The 5-HTTLPR variant was genotyped according to published protocols.
One-year prevalent MDD criteria were met by 298 study participants. The experience of social adversity (both in childhood and adulthood) was strongly associated with increased rates of past-year prevalent MDD. No gene by environment (GxE) interactions between the 5-HTTLPR genotype, social adversity, and MDD were observed.
This study has not replicated a previous finding of a GxE interaction between the 5-HTTLPR genotype, social adversity, and depression.

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    • "Vulnerability to depression following adverse childhood exposures has been observed to be modulated by 5-HTTLPR polymorphism, with carriers of the short (S) allele having increased risk although not consistently (Karg et al., 2011; Risch et al., 2009). The reverse risk has also been observed, with carriers of the L allele being more vulnerable, and this has been related to insecure attachment, family adversity and lower resilience capacity in younger (Olsson et al., 2005; Laucht et al., 2009; Carli et al., 2011 ) as well as in older populations (Surtees et al., 2006; Ritchie et al., 2009). We only found a weak association in men with the S allele being protective which disappeared after adjustment for early adverse events including parental risk. "
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    • "In recent years, studies have suggested an important interplay between genetic and environmental factors in the pathophysiology of MDD (Surtees et al., 2006). Epigenetic regulatory processes have now come into the spotlight to explain the mediating role of social environmental factors, such as childhood adversity or stressful life events, on gene expression (Carballedo et al., 2012b). "
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