Project Summary

Jorge A. Quiroz, M.D. (Young Investigator 2004) of the National Institute of Mental Health, aims to study why sleep deprivation (SD) may have an antidepressant effect. Recent studies show acute SD rapidly upregulates mediators of neuronal plasticity, most notably CREB and BDNF, effects which depend upon noradrenergic system activation. CREB and
BNDF are upregulated by chronic antidepressant use and underlie the delayed therapeutic effects of the drug. Furthermore, the locus coeruleus (LC) noradrenergic projection is quiescent only during rapid eye movement sleep (REM), when the target tissues display their greatest sensitivity. Dr. Quiroz hypothesizes that activating the quiescent noradrenergic system during REM sleep will upregulate CREB and BDNF, and create a rapid antidepressant effect. In his proposed study, Dr. Quiroz plans on using yohimbine, a noradrenergic activator, on major depressive patients to first select those who experience total SD. Responders to total SD who subsequently relapse will then participate in a double-blind crossover study of either a single dose of intravenous yohimbine or placebo (saline solution), during REM sleep. A psychiatric scale will measure the effectiveness of the treatment on depression. If the noradrenergic system activation does provoke the antidepressant effect of SD, then an acute antidepressant effect should be observed in patients after receiving yohimbine, despite minimal or no disruption of sleep. Results could lead to the novel strategically timed-release medications for the rapid depression treatment.

Program Area: MOOD DISORDERS\Unipolar Depression

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