The effects of estradiol on subcortical brain volumes in perimenopausal-onset depression.

Background: Perimenopause is associated with increases in depressive and vasomotor symptoms (VMS), which can be alleviated with transdermal estradiol (TE2) administration. Subcortical brain regions are commonly implicated in depression, are dense with E2 receptors and are susceptible to volumetric changes resulting from E2 regulation of synaptic density. No studies have examined linkages among TE2 administration, perimenopausal-onset major depression (PO-MDD) and subcortical brain volumes.

Methods: This is an exploratory data analysis of change in subcortical brain volumes measured via 3 T MRI before and after three-weeks of TE2 administration in 14 women with PO-MDD and 17 euthymic controls. Regions of interest were the hippocampus, amygdala, putamen, thalamus, and caudate nucleus. Multilevel models examined relations between baseline volumes and volumetric changes with symptom trajectories in the PO-MDD group.

Results: In the PO-MDD group, anhedonia (p < 0.004) and VMS (p < 0.001) significantly reduced following TE2 administration. There was a significant Group X Time interaction in the right hippocampus (p < 0.01), driven by volume increases in the control group (p < 0.001). In the PO-MDD group, change in right hippocampal volumes significantly predicted decreases in anhedonia trajectories from baseline to week 2 and week 3 (p's < 0.001) and decreases in VMS across all timepoints (p's < 0.001).

Discussion: Women with PO-MDD, who presented with more severe baseline anhedonia and VMS, experienced greater reductions in anhedonia, VMS, and hippocampal volumes, demonstrating a greater response to E2. Hippocampal volume change may be a candidate for predicting treatment response to E2 for anhedonia and vasomotor symptoms in women with PO-MDD. These findings should be validated with a placebo-controlled trial.