Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.790080
Title: Neural and cognitive mechanisms underpinning novel treatments for depression
Author: Lally, N.
ISNI:       0000 0004 8503 2967
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2016
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Abstract:
Depression is a prevalent and debilitating psychiatric condition. However, currently available pharmacological treatments are ineffective for almost a third of all depressed patients. Moreover, even when effective, standard treatments suffer from substantial therapeutic lag, often taking weeks-to-months to reach maximum efficacy. Thus, the need for faster acting treatments for depression is high. Evidence of novel glutamatergic pharmacological and brain stimulation antidepressant treatments has been reported. However, it is unknown how exactly these treatments, namely transcranial direct current stimulation and ketamine, work at either the biological or cognitive level. The aim of this thesis was to provide a cognitive and systems level biological explanation for the efficacy of these treatments on two important symptoms of depression, anhedonia and cognitive control. Following a general introductory chapter, the first experimental chapter explores the effect of tDCS on cognitive control in healthy volunteers. The second experimental chapter explores the reliability of 7 Tesla (T) proton magnetic resonance spectroscopy (1HMRS) as a technique to quantify glutamate and glutamine levels in the healthy human brain. The third experimental chapter explores the relationship between levels of glutamatergic metabolites, one purported mechanism to which ketamine and tDCS elicit their antidepressant response, and anhedonia in medication-free depressed patients and healthy individuals at baseline and following ketamine and placebo. The fifth and final experimental chapter explores whether ketamine alters the behaviour and neural activity underlying cognitive control in patients with depression. The results suggest that tDCS may induce improvements in cognition in healthy volunteers and that ketamine may improve levels of anhedonia and mood, but not cognition, in depressed patients. Surprisingly, a decrease in 7T 1H-MRS measured glutamine, but not glutamate, levels was found post-ketamine; moreover, baseline levels of glutamine, but not glutamate, were associated with the antidepressant and anti-anhedonic response to ketamine. The final chapter discusses the experimental results in light of cognitive and neural mechanisms thought to underpin depression and its treatment.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.790080  DOI: Not available
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