In this experiment, we proposed to study the efficacy of quetiapine relative to citalopram in patients with MDD and high risk serotonin transporter gene polymorphism (5-HTTLPR)S/Lg alleles. Since 5-HTTLPR-S/Lg allele confers vulnerability to depression in the context of emotional stress (Caspi et al., 2003) and also mediates poor and slower response to SSRI antidepressants (Serretti et al., 2007), a study of this nature will have significant treatment implications in depressed patients with high risk for stress induced relapses and treatment resistance. Given that quetiapine has no affinity for 5-HTT and may normalize the receptor changes that occur in conditions with low 5-HTT expression (S and Lg carriers and patients with MDD), we predict that compared to citalopram treatment, quetiapine treatment will be more effective in reducing amygdala responses to negative stimuli as well as depressive symptoms in patients with MDD and high risk S/Lg alleles. It is also predicted that because of its direct action on post synaptic 5-HT1A and 5-HT2A receptors, quetiapine treatment will show early onset of action on amygdala responses than citalopram treatment especially in patients with S allele.