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Title: Mood instability : its cognitive and neural correlates and the effects of L-type calcium channel antagonism
Author: Atkinson, Lauren
ISNI:       0000 0004 9355 3869
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2020
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Mood instability is commonly experienced in the general population. It is associated with risk for subsequent diagnosis of bipolar disorder (BD) and is a prominent feature of several other psychiatric disorders. Despite the significance of mood instability in psychopathology, there is little research examining its potential underlying mechanisms. In a study measuring mood, cognitive function and resting-state magnetoencephalography (MEG) over 10-weeks, the first part of this thesis aimed to characterise mood instability and explore its cognitive and neural correlates in healthy individuals at low and high risk of BD as indicated on the Mood Disorder Questionnaire (MDQ). Findings demonstrated that instability in negative mood was significantly different between individuals scoring low and high on the MDQ. Individuals with high MDQ scores demonstrated deficits in learning context-based regularities across days, and higher levels of negative mood instability in this group were also associated with changes in neural activity such as reduced switching between brain states, and reduced time spent in a fronto-limbic state thought to be necessary for mood regulation. The second part of this thesis aimed to explore the candidacy of L-type calcium channel (LTCC) antagonism as a potential treatment for mood instability. Healthy individuals with high MDQ scores participated in a double-blind, placebo-controlled, experimental medicine study. For two weeks in the absence of any intervention, measures of mood and neural activity were assessed. This was followed by a 2-week randomisation phase to either nicardipine SR or placebo, during which all measures were repeated. Compared to placebo, LTCC antagonism was not found to reduce mood instability or significantly affect resting-state MEG measures of spectral power, alpha peak frequency, or characteristics of fast transient brain states. Overall, these findings provide insights into the potential mechanisms that might underlie mood instability, highlighting areas for future investigation. While the candidacy of LTCC antagonism in mood instability was not confirmed, this work demonstrates the feasibility of multimodal, high-intensity studies to investigate transdiagnostic constructs and the potential of new treatments.
Supervisor: Nobre, Anna ; Harrison, Paul Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Psychiatry ; Experimental Medicine ; Cognitive Neuroscience