Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.658867
Title: Investigating cognitive neuropsychological mechanisms in depression
Author: Stuart, Sarah Ann
ISNI:       0000 0004 5356 7051
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2014
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Abstract:
Recent evidence from studies using cognitive neuropsychological testing in human depression suggests that specific cognitive mechanisms play an important role in the development and perpetuation of depressive illness. These studies suggest that quantifying objective measures of affective state and affective processing may provide a new opportunity for developing translational animal models. This thesis describes the validation of a novel behavioural approach, the affective bias test CABT) designed to facilitate the investigation of cognitive affective processing biases in rodents. Pharmacological and psychosocial anti- and prodepressant treatments were shown to induce affective biases that are predictive of their effects in man. These effects were shown to increase with successive experiences encountered during affective treatment, and the data suggest that the treatments may act by modifying the consolidation of affective memory. The NMDA antagonist ketamine was observed to attenuate acquired negative affective biases via disruption of neurotransmission in the prefrontal cortex, while the monoamine reuptake inhibitor venlafaxine positively biased new learning through actions in the amygdala. This pattern of results suggests that the neuropsychological mechanisms of delayed- and rapid-onset antidepressants are neurally and temporally dissociated. A pilot study was also conducted to investigate the hypothesis that negative affective biases induced by prolonged negative affective state generalise to behaviours associated with social and exploratory behaviour, and this study has provided a methodological basis for future studies investigating the role of chronic stress in depression. Together the work presented in this thesis supports a cognitive neuropsychological mechanism for the development and treatment of depression and demonstrates face, predictive and construct validity for the ABT as a preclinical assay for use in drug safety and development.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.658867  DOI: Not available
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