Extraversion modulates cortisol responses to acute social stress in chronic major depression.

BACKGROUND: Chronic Major Depressive Disorder (CMDD) is a common, disabling illness that is often complicated by high reactivity to social stress. To further elucidate the nature of this reactivity, the current study evaluated whether the personality dimensions of neuroticism and extraversion influenced cortisol responses to a social challenge in CMDD patients vs. controls. METHODS: Fifty participants with CMDD and 58 healthy controls completed the Trier Social Stress Test (TSST) using a standard protocol. Neuroticism and extraversion were measured using the Revised NEO Personality Inventory. Hierarchical linear regressions assessed associations between independent variables neuroticism and extraversion and dependent variable cortisol area-under-the-curve increase (AUCi) in response to the TSST in the two study groups. RESULTS: The extraversion-by-group interaction was a significant predictor of cortisol AUCi, while no significant findings related to neuroticism were found. Simple slopes analysis revealed a significant negative association between extraversion and AUCi in the CMDD group, but not in healthy controls. Post-hoc analysis of the raw cortisol data over time found that CMDD participants with higher extraversion scores had significantly higher pre-challenge cortisol levels than did other study participants, however this did not explain or confound the AUCi results. CONCLUSIONS: In participants with CMDD but not in controls, higher levels of extraversion were associated with higher pre-challenge cortisol levels and decreased cortisol reactivity during the TSST, however these two findings were statistically independent. These findings underline the importance of considering personality factors when studying stress biology in CMDD patients. Extraversion may prove to be an important intermediate target for both research and clinical work in this complex, heterogenous and often treatment-resistant population.

Rat hepatocyte culture model of macrosteatosis: effect of macrosteatosis induction and reversal on viability and liver-specific function.

BACKGROUND & AIMS: A common cause of liver donor ineligibility is macrosteatosis. Recovery of such livers could enhance donor availability. Living donor studies have shown diet-induced reduction of macrosteatosis enables transplantation. However, cadaveric liver macrosteatotic reduction must be performed ex vivo within hours. Towards this goal, we investigated the effect of accelerated macrosteatosis reduction on hepatocyte viability and function using a novel system of macrosteatotic hepatocytes. METHODS: Hepatocytes isolated from lean Zucker rats were cultured in a collagen sandwich, incubated for 6 days in fatty acid-supplemented medium to induce steatosis, and then switched for 2 days to medium supplemented with lipid metabolism promoting agents. Intracellular lipid droplet size distribution and triglyceride, viability, albumin and urea secretion, and bile canalicular function were measured. RESULTS: Fatty acid-supplemented medium induced microsteatosis in 3 days and macrosteatosis in 6 days, the latter evidenced by large lipid droplets dislocating the nucleus to the cell periphery. Macrosteatosis significantly impaired all functions tested. Macrosteatosis decreased upon returning hepatocytes to standard medium, and the rate of decrease was 4-fold faster with supplemented agents, yielding 80% reduction in 2 days. Viability of macrosteatosis reduced hepatocytes was similar to control lean cells. Accelerated macrosteatotic reduction led to faster recovery of urea secretion and bile canalicular function, but not of albumin secretion. CONCLUSIONS: Macrosteatosis reversibly decreases hepatocyte function and supplementary agents accelerate macrosteatosis reduction and some functional restoration with no effect on viability. This in vitro model may be useful to screen agents for macrosteatotic reduction in livers before transplantation.