Major depression (MD) is projected to become the world's second leading cause of disability by 2020 [Murray and Lopez, 1996]. Despite heritability estimates of MD ranging from 31% to 42% [Sullivan et al., 2000], few genetic variants have been discovered [Lopez-Leon et al., 2008]: one of the most studied is the length polymorphism repeat (LPR) in the promotor region of the serotonin transporter gene (5HTT renamed SLC6A4). The 5HTTLPR polymorphism comprises a 43-bp insertion or deletion (long, “L,” or short, “S,” alleles, respectively) [Nakamura et al., 2000; Hu et al., 2005, 2006; Kraft et al., 2005; Wendland et al., 2006]. The S allele reduces transcriptional efficiency, resulting in decreased SLC6A4 expression and 5HTT uptake in lymphoblasts [Lesch et al., 1996]. Meta-analyses show a small association between suicide and 5HTTLPR [Li and He, 2007] and an inconsistent association between MD and 5HTTLPR with effects observed by some [Serretti et al., 2007; Lopez-Leon et al., 2008] but not others [Anguelova et al., 2003; Lasky-Su et al., 2005; Levinson, 2005].
