Circadian Rhythm Resynchronization as a Targeted Intervention for Mood Stability in Bipolar Disorder.

Abstract

The circadian rhythm is a ubiquitous process, primarily regulated by the fluctuation in light and temperature. Research has shown that the implication of the circadian rhythm spans all aspects of physiology, including cognitive and mood functions. The circadian rhythm is a highly conserved transcriptional translational feedback loop. Specifically, the protein products of Bmal1 and Clock genes heterodimerize outside the nucleus and re-enter to activate their repressing genes. All nucleated cells in mammalian body express this intrinsic clock, and all the tissues are synchronized by the Suprachiasmatic Nucleus (SCN) of the hypothalamus which receives light information from the retina. Emerging evidence shows that dysregulation of the circadian rhythm underlies the symptoms of many neurocognitive conditions such as bipolar disorder. The release of all neurotransmitters is circadian regulated. Therefore, studies that characterize the role of circadian rhythmicity in regulating cognitive and mood function in BD are essential for illuminating the therapeutic path. The efficacy of entrainment in managing symptoms of BD has been shown previously. Additionally, common therapeutic interventions for BD such as valproic acid, SSRIs and lithium have been shown to impact the circadian rhythm, partially explaining their therapeutic effect. I propose a bench protocol for enhancing the rhythmicity of SCN human explants. This will provide groundwork an in-patient regimen that stimulates the SCN activity through methods shown success in culture. I hypothesize that returning the circadian cycle in BD to a rhythmic baseline leads to physiological changes that are observable by the patient and psychiatrist in an encounter, such as changes in sleep quality and melatonin level in saliva. This approach can also promote insight and help the patient regulate their activities and emotions to improve their mood symptoms. The jet lag phenomenon is a stark example of observable physiological changes, showing that circadian reset provides the thermodynamic potentiality for introspection.