Major depressive disorders (MDD) is a chronic, recurring and potentially life threatening illness that affects up to 20% of the global population. Furthermore, the world Health Organization (WHO) has predicted that mood disorders such as depression will be the leading contributor to the global burden of disease within the next few years. Progress in treatment for cardiovascular disease and cancer has progressed rapidly over the years while the current treatment strategies for depression are predominantly based on the monoamine hypothesis developed on findings from 60 years ago. One of the leading problems with the standard treatments is that a) only 40% of patients exhibit full remission, b) in those patients that do respond to treatment the positive effects can take weeks or months to take place and c) side effects are still a major issue. In light of this there is an urgent need to develop better therapeutics for the treatment of depression.
Though counterintuitive, sleep deprivation therapy (SDT) can rapidly alleviate symptoms of depression. Since the majority of patients suffering from MDD exhibit abnormal circadian rhythms in mood and sleep, a leading hypothesis for the effectiveness of SDT for the treatment of depression postulates that sleep deprivation (SD) resets abnormal circadian machinery. The cellular and molecular changes associated with SD induced rapid reversal of depression are unknown. Chronically Sleep Deprivation itself can be harmful to a patient’s wellbeing, however, by understanding the cellular and molecular changes associated with the treatment effects of SD on depression it would be possible to develop targeted medicinal therapeutics for the rapid treatment of depression. Recent technical advances such as optogenetics and in vivo imaging combined with viral tracing and electrophysiology make it feasible to map and functionally determine the therapeutic effects of SD on depression at the neural circuit level.
The Chaudhury Lab uses a multidisciplinary approach combining rodent behavioural models of depression, optogenetics, in vitro and in vivo electrophysiology, viral tracing, pharmacological and imaging techniques to systematically investigate functional changes in cellular and molecular mechanism in neural circuits connecting the circadian and sleep/wake centers of the brain to regions associated with mood disorders such as depression.
Example of putative molecular pathways linking circadian and sleep regulation of neural dynamics in regions associated with mood disorders.
Neural circuit linking sleep-wake and circadian centers of the brain to regions associated with regulation of mood.
