Interactions between the serotonin transporter gene and early life environment: Effects on anxiety and anhedonia

Abstract

The development of generalised anxiety and major depressive disorders have overlapping aetiologies driven by both genetic and environmental influences. Study of the serotonin transporter (SERT) gene, SLC6A4 has shown that allelic variants linked to reduced SERT expression interact with early-life maltreatment to increase the likelihood of developing anxiety and depression. However, it has also been proposed that genetically reduced SERT expression increases sensitivity to the environment, implying that such genetics would enhance the protective effects of a nurturing early-life environment. The current study aimed to investigate the effects of such gene by environment interactions on anxiety- and depression-like behaviour in an experimental model. Female heterozygous (SERT+/-) and homozygous (SERT-/-) SERT knockout rats were used to model the genetically reduced SERT expression of humans. A 24 hr period of maternal deprivation on postnatal day 9 and early handling from postnatal days 2 – 14 were used to model adverse and nurturing early-life environments respectively. The effect on anxiety-like behaviour was examined through the successive alleys and novelty suppressed feeding paradigms, while anhedonia-like behaviour was examined through the anticipatory locomotor activity and pleasure attenuated startle paradigms. While no main effect of environment, or interaction between genotype and environment were found, there was a main effect of genotype. This revealed that SERT-/- rats showed greater anxiety- and anhedonia-like behaviour than their wildtype and SERT+/- counterparts. From these results, it was concluded that the environmental manipulations used were insufficient to alter anxiety- and anhedonia-like behaviour, which could be the result of other resilience factors. It was also concluded that SERT expression influences the development of anxiety and depression, but up to a point, the behavioural consequences of reduced SERT expression are buffered by protective mechanisms.