Altered serotonergic neurotransmission is hypothesized to be central to the pathogenesis of a wide variety of CNS disorders including migraine headaches, major depression (MD), autism and alcoholism [Glover et al., 1993; Conroy et al., 2004; Feinn et al., 2005]. The serotonin transporter (5HTTor SLC6A4) is a key regulator of serotonergic neurotransmission. This gene, which is localized to 17p13, consists of 14 exons and a single promoter [Lesch et al., 1994]. Two structural elements of SLC6A4 are of particular relevance to this communication. The first is a variable nucleotide repeat (VNTR), referred to as 5HTTLPR, which is approximately 1,400 bp upstream of the transcription start site [Collier et al., 1996; Heils et al., 1996]. The second is a recently discovered CpG island that surrounds Exon 1 [Philibert et al., 2007a].
