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UBC Theses and Dissertations

Executive function deficits in bipolar I disorder : association with brain structure, illness progression, and antipsychotic medication Kozicky, Jan-Marie Elena


Executive function impairments are a core feature of Bipolar I Disorder (BDI), present not only during acute episodes but also persisting following remission of mood symptoms. Despite advances in knowledge regarding the neural basis of executive functions (EF) in healthy subjects, particularly in regards to the role of the dorsolateral prefrontal cortex (DLPFC) and caudate; research into how changes within these regions contribute to the deficits in BDI is lacking. This thesis explores EF in patients early in the course of illness, examining how impairments evolve with illness progression and how this may relate to neuromorphological changes and naturalistic pharmacological treatment regimes. The first analysis demonstrates that EF is moderate-severely impaired in patients with BDI even following sustained symptomatic recovery from their first manic episode. Both larger caudate size and treatment with a higher relative dose of an antipsychotic drug predicted the severity of deficits. Despite receiving ongoing clinical care, half of patients experienced a subsequent hypo/manic and/or depressive episode within one year. While those who remained well did show significant improvements in EF compared to those whose illness progressed, both patient groups still maintained moderate deficits compared to healthy subjects at follow-up. Although not directly associated with cognitive changes, sustained recovery during this time was also associated with reduced grey matter loss (including the left DLPFC) when compared affective recurrence, even after accounting for other clinical or treatment factors. Maintenance pharmacological treatment with an antipsychotic is commonly used to prevent episode recurrence in BDI. Drugs within this class each show varying affinity to the dopamine D₂ receptor (D₂R), which plays an important modulatory role in DLPFC and caudate function. Differences in D₂R binding have a likely impact on EF, as patients receiving an antipsychotic with high D₂R affinity (risperidone) showed larger impairments when compared to those treated with a low affinity drug (quetiapine) or no antipsychotic. These results demonstrate that illness related structural changes in the DLPFC and caudate are associated with the presence and evolution of executive function deficits in BDI; although the potential confounding effects of antipsychotics which influence functioning in these regions must also be considered.

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