UC San Diego

Circadian rhythms are endogenous biological rhythms that oscillate on a 24-hour period. Dysfunction in the circadian system has been implicated in mood disorders, including bipolar disorder (BD). While genetics can explain 60-80% of the variance in expression of this disorder, 20-40% is unaccounted for and could be due to psychosocial factors such as stress. We hypothesized that cells from patients with BD would be more susceptible to rhythm alterations than those of healthy controls when exposed to conditions modeling stress. In order to explore our hypothesis we employed dexamethasone, a synthetic version of the glucocorticoid hormones that are released in response to stress via the hypothalamic-pituitary- adrenal axis. We used qPCR to examine expression of genes indicating cellular stress and bioluminescent reporter assays of clock gene expression to examine circadian rhythm parameters of period, amplitude, and goodness-of- fit. We report that there are no differences in response to dexamethasone between the control and BD cells for period and amplitude. However, we found significant differences in goodness-of-fit, suggesting that glucocorticoid mediated stress could provoke symptoms of BD through a circadian clock mechanism