Antidepressants and the early processing of threat

Cognitive models emphasise the role that heightened attentional vigilance towards potentially threatening stimuli plays in the development and maintenance of anxiety disorders. These threat-related cognitive biases are a major focus of psychological therapeutic interventions for anxiety and there is evidence that they are reduced following successful psychological treatment. Antidepressants, such as the commonly prescribed selective serotonin reuptake inhibitors (SSRI), are effective in the treatment of depression and anxiety disorders. \X'hilst the pharmacological action of these agents is well understood, little is known about why these chemical changes result in symptom remission and mood change. The current thesis aimed to extend understanding of the neuropsychological mechanism of action of serotonergic antidepressants. More specifically, the aim was to investigate whether SSRIs affect selective attention to threatrelated stimuli in an opposite manner to the threat-related biases in information processing that are known to play a central role in the aetiology of anxiety disorders. Characterising the cognitive effects of pharmacological agents such as SSRIs has important implications for our understanding of how these drugs work and ultimately how they can be improved and integrated with psychological theories of anxiety and treatment. .A series of behavioural and neuroimaging studies was conducted looking at the effect of anxiolytic pharmacological challenge on the cognitive processing of threat, and the neurocircuitry underpinning these processes in healthy volunteers. At a behavioural level two different classes of anxiolytic agent (the SSRI citalopram and the benzodiazepine diazepam) were shown to modulate attentional biases away from threat-related stimuli. These effects occurred in healthy volunteers, in the absence of any subjective changes in mood or anxiety, suggesting that the modulation of attentional vigilance away from threat-related stimuli may represent a direct and common psychological mechanism of pharmacological anxiolytic action. Using pharmacological £IvIRI, it was demonstrated that the SSRI citalopram modifies the neural processing of threat-related stimuli in a manner that is consistent with these behavioural effects. Specifically, acute administration of citalopram was shown to reduce the amygdala response to fearful faces compared with placebo in healthy volunteers. The final two studies of this thesis were designed to specifically probe the effect of citalopram on the neural circuitry involved in the processing of task-irrelevant threat-related stimuli. These studies demonstrated that short term administration of citalopram modulates the neural processing of emotional information in stimulus-specific posterior processing areas. As a whole, the studies in this thesis provide behavioural and neuroimaging support for the idea that citalopram administration rapidly reduces emotional processing biases to task-irrelevant threatrelated stimuli, which may be an important component of the anxiolytic action of this drug.EThOS - Electronic Theses Online ServiceGBUnited Kingdo