An exploration of the role L-type calcium channels in mood, cognition and sleep. (360G-Wellcome-211024_Z_18_Z)

I plan to explore the effect of nicardipine, a brain-penetrant calcium channel antagonist, on mood instability and its cognitive/neural correlates. This research (carried out within the Collaborative Oxford Network for Bipolar Research to Improve Outcomes [CONBRIO]) has a number of goals. In addition to studying effects of L-type calcium channel (LTCC) antagonism on mood instability, I will investigate effects on sleep/cognition, and on brain activity measured by functional imaging. Rationale is provided by (a) considerable evidence for calcium signalling abnormalities in bipolar, (b) current mood stabilisers correct some of these abnormalities, (c) calcium channel genes contribute to the basis of bipolar as well as to memory/sleep. Moreover, LTCC antagonists are used for heart disease and available for experimental studies; there have also been early studies in bipolar disorder but no robust results. I will study volunteers screened for high mood instability and risk CACNA1C genotype, and assess mood, sleep, cognition, and neural activity, before and after randomisation to nicardipine or placebo. Results will inform whether trials of LTCC antagonists for bipolar disorder are indicated, and their likely efficacy/tolerability. I will learn to conduct a randomised trial, principles of experimental medicine, and aspects of cognition, circadian-biology, and functional brain imaging.