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Title: Neurocognitive risk and protective factors in addictive disorders
Author: Smith, Dana
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2014
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Cognitive impairments and changes in the structure and function of related brain regions, namely the prefrontal cortex and striatum, have long been implicated in drug addiction. However, it is unknown whether these abnormalities predate substance abuse, potentially serving as risk factors for dependence, or if they are the consequence of protracted use. To address this question, endophenotype research using stimulant-dependent individuals’ biological siblings has been used to investigate traits implicated in the pathology of addiction. Impairments present in both groups suggest an underlying risk-state for dependence, while additional abnormalities present only in stimulant-dependent individuals reflect potential effects of the drugs themselves. Contrastingly, there are also individuals who use stimulant drugs in a controlled manner without developing dependence. These ‘recreational users’ may lack the underlying traits that comprise a greater risk for dependence, or they might maintain additional protective factors against the development of addiction. Experiments in the first half of this dissertation used functional magnetic resonance imaging to investigate neurocognitive similarities and differences between dependent stimulant users, their non-dependent siblings, recreational users of cocaine, and unrelated healthy control volunteers. In Chapter 2, performance on a colour-word Stroop task was impaired in both stimulant-dependent individuals and their siblings, suggesting an endophenotype of cognitive inefficiency. However, neural activity significantly differed between the groups, indicating additional changes specific to the use of stimulant drugs. In Chapter 3, dependent users showed significant attentional bias to salient stimuli on a cocaine-word Stroop task, with a concurrent increase in prefrontal activation. Conversely, recreational users showed resilience in the face of cocaine cues and a decrease in arousal. Finally, Chapter 4 explored differences in reward sensitivity to both generic and drug-specific reinforcers, comparing the effects of personal and family history of stimulant exposure on a monetary incentive delay task. It is also under debate whether the neurocognitive differences seen in stimulant-dependent individuals are unique to substance abuse, or if parallel changes in behaviour and neurobiology are present in similar addiction-spectrum disorders, such as binge eating leading to obesity. In Chapter 5, stimulant-dependent and obese individuals with binge-eating behaviours showed differences in their substance-specific and general reward responsivity on a novel reward-valuation task. However, in Chapter 6 a similar decline in orbitofrontal cortex grey matter volume in relation to both years of stimulant use and body mass index was identified, implicating an overlap in this area between both conditions. These findings are integrated in Chapter 7, discussing the neurocognitive risk and protective factors that underlie an individual’s vulnerability for addiction, not only to stimulant drugs, but also potentially for other addictive behaviours.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: Addiction ; fMRI ; Prefrontal cortex ; Reward ; Impulsivity ; Binge eating