Neural Signaling of Cortisol, Childhood Emotional Abuse, and Depression-Related Memory Bias

Abstract Background Cortisol has potent effects on learning and neuroplasticity, but little is known about its effects on negative memory biases in depression. Animal models show that aversive caregiving alters effects of glucocorticoids (primarily corticosterone in rodents and cortisol in primates) on learning and neuroplasticity into adulthood. Methods We investigated whether history of childhood emotional abuse (EA) moderated effects of cortisol administration (CORT) versus placebo on emotional memory formation in depression. Participants included 75 unmedicated women with varying levels of depression severity and/or EA history. In a double-blind crossover investigation, we used functional magnetic resonance imaging to measure effects of CORT (vs. placebo) on neural function during emotional memory formation. Results CORT eliminated the well-known relationship between depression severity and negative memory bias, a finding explained by EA severity. For women with a history of severe EA, CORT reduced depression-related negative memory bias and normalized recall for pleasant stimuli. EA severity also moderated CORT effects on neural function: in women with history of severe EA, CORT increased activation in the supplementary motor area during viewing of unpleasant relative to pleasant pictures. Additionally, supplementary motor area activation predicted reduced negative bias for pictures encoded during CORT. Conclusions These results suggest that increasing cortisol signaling may be neurocognitively beneficial in depressed women with a history of maltreatment. The findings corroborate prior research suggesting that presence or absence of adverse caregiving is etiologically important in depression. These findings suggest potential neurocognitive mechanisms of therapeutics targeting cortisol signaling, which show promise in treating affective disorders.