Cortisol effects on brain functional connectivity during emotion processing in women with depression.

Background: Depression is associated with altered functional connectivity and altered cortisol sensitivity, but the effects of cortisol on functional connectivity in depression are unknown. Previous research shows that brief cortisol augmentation (CORT) has beneficial neurocognitive effects in depression.

Methods: We investigated the effects of CORT (20mg oral cortisol) on functional connectivity during emotion processing in women with depression. Participants included 75 women with no depression or a depressive disorder. In a double-blind, crossover study, we used functional magnetic resonance imaging to measure effects of CORT vs. placebo on task-based functional connectivity during presentation of emotionally-laden images. We performed psychophysiological interaction (PPI) to test interactions among depression severity, cortisol administration, and task-dependent functional connectivity using the hippocampus and amygdala as seeds.

Results: During the presentation of negative images, CORT (vs. placebo) increased functional connectivity between the hippocampus and putamen in association with depression severity. During the presentation of positive pictures CORT increased functional connectivity between the hippocampus and middle frontal gyrus as well as superior temporal gyrus in association with depression.

Limitations: Because cortisol was pharmacologically manipulated, results cannot be extrapolated to endogenous increases in cortisol levels. The sample did not permit investigation of differences due to race, ethnicity, or sex. Co-morbidities such as anxiety or PTSD were not accounted for.

Conclusions: The results suggest that CORT has normalizing effects on task-dependent functional connectivity in women with depression during emotion processing. Increasing cortisol availability or signaling may have therapeutic benefits within affective disorders.