Serotonin Transporter Genetic Variation and Amygdala Responses to Antidepressant Medications in Major Depression

Major depressive disorder (MDD) is a highly prevalent, chronic and/or recurrent condition with substantial morbidity and mortality. It is one of the leading causes of disability worldwide. Despite significant advances in pharmacological treatment for depression over the last two decades, a significant proportion of patients (10-20%) are resistant to currently available treatment. The development of new effective treatment for depression is limited by the fact that MDD is a heterogeneous disorder with subgroups based on variations in etiological factors and treatment response. Functional magnetic resonance imaging (fMRI) approaches offer promise in the prediction and evaluation of clinical response of antidepressant treatment. Previous fMRI studies have identified increased activity in dorso-lateral prefrontal cortex (DLPFC) and decreased amygdala activity from the baseline as imaging markers of antidepressant response in patients with MDD. However, these studies have examined MDD as a homogenous group without specifying the type of patient group, and brain regions as a priori hypothesis.We therefore need studies using combined genetics and neuroimaging measures as biomarkers in the prediction and evaluation of clinical response to antidepressants. In this study we attempted to determine imaging clinical efficacy markers in previously defined brain regions (amygdala and prefrontal regions) for two classes of antidepressants (citalopram and quetiapine extended release (XR)) with differential action on serotonin transporter inhibition in a subgroup of MDD patients with high risk allele ( S/Lg) of serotonin transporter gene polymorphism.