Major Depressive Disorder is a debilitating illness that impacts 1 in 6 people in the United States during their lifetime. Particularly when monoamine levels are low, depression is associated with reduced volume in the front-limbic-striatum emotional processing network. Catechol-O-Methyltransferase (COMT) is responsible for most dopamine degradation in the frontal cortex. Guided by past literature, we examined the effect of COMT genotype on white matter integrity in the amygdala, hippocampus and parahippocampus in depressed patients along with healthy controls. Our results suggest the existence of sex-genotype interaction which is clinically relevant for women suffering from depression.