Recall test for previously encoded words Acute cortisol elevations bias memory formation in a negative direction only in depressed individuals with a history of early loss Heather C. Abercrombie PhD1, Allison L. Jahn PhD2, & Roxanne M. Hoks1 1Department of Psychiatry, University of Wisconsin School of Medicine & Public Health; 2VA Boston Healthcare System Poster sponsored by David Spiegel, MD Do enduring qualities of individuals (e.g., early life experiences or affective style) moderate the effects of stress hormones on emotional memory? Recent research in our laboratory in healthy humans has shown that affective style moderates the effects of cortisol on memory formation.1 In adult rats, a history of low maternal care biases learning toward threatening contexts, and alters the effects of corticosteroids on neuroplasticity in the hippocampus.2,3 In humans, depressed adults with a history of adversity show greater dysregulation in cortisol than do depressed adults without history of adversity.4 However, it is unknown whether the effects of cortisol on memory formation in humans vary as a function of the early environment. We hypothesized that history of early loss in depressed adults would moderate the effects of cortisol administration on formation of negatively biased memories. An increase in negative recall bias for words encoded on the CORT (vs. placebo) day was found for depressed adults with history of loss, but CORT did not significantly alter recall bias in depressed adults without history of loss, t(16) = 2.55, p < .03. In summary, acute cortisol elevation caused an increase in negative recall bias in depressed participants with a history of early loss due to parental divorce, but cortisol elevation did not alter recall bias in those without history of loss or adversity. These findings in depressed adults replicate animal literature showing that individual differences in early life experience moderate corticosteroids’ effects on learning.2,3 The results further substantiate research suggesting that history of early adversity vs. no adversity engenders distinct depressive subtypes, especially with regard to hypothalamic pituitary adrenal functioning.4 Possibly, early adversity causes long-lasting sensitization of neural processes associated with threat-related learning, and acute cortisol elevation may heighten threat-related learning in those with a history of early loss. The current findings come from a small sample without a matched control group, and therefore must be replicated. If replicated, the findings have significance for personalized medicine, and lay the groundwork for research on treatment selection based on early history. Corticosteroid receptor ligands show promise as treatment augmentation strategies for depression.5,6 Research is needed to determine whether history of early adversity predicts the efficacy of pharmacological alteration of cortisol signaling in depression. Although cortisol alterations in depression have been studied for decades, the role of cortisol in psychological features of depression is relatively unknown. This research has the potential to bring the vast research on cortisol’s effects on emotional memory to the study of cortisol’s role in depression. RESULTS DISCUSSION INTRODUCTION The data are significant when including men and women (shown above). When separating the data by sex, the effect is apparent only in women. CORT (vs. placebo) biased recall in a negative direction by an average of 4.2 (.73) words in depressed women with history of early loss. CORT had no effect in depressed women who did not experience early loss, with CORT altering bias by an average of only 0.2 (1.2) words. Thus, the finding is driven primarily by women. No differences were found for perceived stress, depression severity, or at-home endogenous cortisol for participants with vs. without early loss, p’s > 0.29. Furthermore, the moderating effects of early loss on CORT’s effects on recall bias remained significant after first accounting for these variables, p’s < .05. In a repeated measures design (see schematic below), 18 unmedicated depressed adults (10 women) received 15 mg oral hydrocortisone (i.e., cortisol; CORT) or placebo on two different days separated by 48 hours. Drug administration was double-blind and counterbalanced (i.e., half of the participants received CORT on Day 1, and the other half received placebo on Day 1). One hour after drug administration, participants encoded unpleasant and pleasant words. Free recall for words was tested several days later, and recall bias was calculated (pleasant minus unpleasant words recalled) for words encoded on the CORT and the placebo days. Schematic of study procedures: METHODS Recall test for previously encoded words Beginning 4:30 PM CORT 15 mg Counterbalanced Phone Screen Screening Visit Day 1 Day 3 Day 7 Placebo 1. Abercrombie HC, Wirth MM, Hoks RM. (in press). Psychoneuroendocrinology. 2. Champagne DL, et al. (2008). The Journal of Neuroscience. 3. Bagot RC, et al. (2009). Neurobiology of Learning & Memory. 4. Heim C. (2008). Psychoneuoendocrinology. 5. Otte C. (2010). Journal of Psychiatric Research. 6. Schatzberg AF & Lindley S. (2008). European Journal of Pharmacology. REFERENCES This research was supported by the NIMH (K08-MH074715), a NARSAD Young Investigator Award, & an NSF Graduate Research Fellowship. All authors report no biomedical financial interests or potential conflicts of interest. Effects of early loss None of the participants experienced early abuse or neglect, but eight of the depressed adults had experienced early loss before age 13 due to parental divorce. We tested whether early loss moderated the effects of CORT (vs. placebo) on negative recall bias. contact: hcabercr@wisc.edu