UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Neural and cognitive mechanisms underpinning novel treatments for depression

Lally, N; (2016) Neural and cognitive mechanisms underpinning novel treatments for depression. Doctoral thesis , UCL (University College London). Green open access

[img]
Preview
Text
Lally_PhD_Thesis.pdf.without signature.pdf

Download (2MB) | Preview

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.

Type: Thesis (Doctoral)
Title: Neural and cognitive mechanisms underpinning novel treatments for depression
Open access status: An open access version is available from UCL Discovery
Language: English
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/1473924
Downloads since deposit
178Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item