Faculty Bibliography

Preclinical studies have shown long-term alterations in several hormonal systems including cortisol, dehydroepiandrosterone (DHEA) and DHEA-Sulfate, and estradiol. The purpose of this study was to assess cortisol, DHEA, and estradiol over a 24-hour period in women with early childhood sexual abuse and posttraumatic stress disorder (PTSD); with early abuse and without PTSD; and women without early abuse or PTSD. Forty-three women with early childhood sexual abuse and PTSD, early abuse without PTSD, and without abuse or PTSD, underwent a comprehensive assessment of hormones in plasma at multiple time points over a 24-hour period. Abused women with PTSD had lower concentrations of cortisol during the afternoon hours (12-8 p.m.) compared with women with abuse without PTSD and women without abuse or PTSD. DHEA-Sulfate was elevated throughout the 24-hour period in PTSD women, although this was of marginal statistical significance. There were no differences between groups in DHEA or estradiol. PTSD women also had increased cortisol pulsatility compared with the other groups. These findings suggest that a resting hypocortisolemia in the afternoon hours with increased cortisol pulsatility is associated with childhood abuse-related PTSD in women.

BACKGROUND: Multiple studies have documented deficits in verbal declarative memory function in depression that improve with resolution of symptoms; imaging studies show deficits in anterior cingulate function in depression, a brain area that mediates memory. No studies to date have examined neural correlates of emotionally valenced declarative memory using affectively negative (sad) verbal material that is clinically relevant to understanding depression. Also no studies have examined the effects of treatment on neural correlates of verbal declarative memory. The purpose of this study was to examine the effects of treatment with antidepressants on verbal declarative memory in patients with depression. METHODS: Subjects with (N=18) and without (N=9) mid-life major depression underwent positron emission tomography (PET) imaging during verbal declarative memory tasks with both neutral paragraph encoding compared to a control condition, and emotional (sad) word pair retrieval compared to a control condition. Imaging was repeated in 13 subjects with depression after treatment with antidepressants. RESULTS: Patients with untreated depression had a failure of anterior cingulate activation relative to controls during retrieval of emotional word pairs. Antidepressant treatment resulted in increased anterior cingulate function compared to the untreated baseline for both neutral and emotional declarative memory. LIMITATIONS: Limitations include a small sample size and variety of antidepressants used. CONCLUSIONS: These results are consistent with alterations in anterior cingulate function that are reversible with treatment in patients with depression. These findings may have implications for understanding the mechanism of action of antidepressants in the treatment of depression.