Amygdala responses to quetiapine XR and citalopram treatment in major depression: the role of 5-HTTLPR-S/Lg polymorphisms.

Objectives: Genotype and drug pharmacology may contribute to variations in brain response to antidepressants. We examined the impact of two antidepressants with differential actions on serotonin transporter and the 5-HHTLPR-S/Lg polymorphisms on amygdala responses in major depressive disorder (MDD).

Methods: Caucasians with MDD were given either citalopram or quetiapine extended release for 8 weeks. Patients were genotyped for 5-HTTLPR. Clinical efficacy was assessed using the Hamilton Depression Rating Scale. fMRI responses to negative emotional faces were acquired at baseline, week 1 and week 8. The outcome measure was change in amygdala responses at week 8.

Results: Citalopram had no effect on amygdala responses in MDD patients with S/Lg alleles at weeks 1 and 8 compared with baseline, whereas it induced changes in amygdala responses in LL homozygotes. By contrast, quetiapine decreased amygdala responses at both time points in S/Lg carriers, and changes in amygdala responses at week 8 correlated with a reduction in depression scores. The small number of LL homozygotes in quetiapine group was a limitation. Efficacy of both treatments was comparable.

Conclusions: These preliminary data suggest that pharmacological mechanisms and genetics need to be considered in the development of neuroimaging markers for the evaluation of antidepressant treatments.