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dc.contributor.advisorMcIntosh, Andrew
dc.contributor.advisorHall, Jeremy
dc.contributor.advisorSibley, Heather
dc.contributor.authorSussmann, Jessika Elizabeth Debora
dc.date.accessioned2019-07-31T09:54:29Z
dc.date.available2019-07-31T09:54:29Z
dc.date.issued2019-07-06
dc.identifier.urihttp://hdl.handle.net/1842/35936
dc.description.abstractAbnormalities of reward processing, decision-making and emotion processing are core features of bipolar I disorder (BD). These processes are closely linked with fronto-striatal and midbrain circuitry. I sought to test whether dysfunctions of these pathways were present in BD and whether they related to genetic vulnerability to illness or resilience. I recruited twenty-five BD I patients each with their unaffected sibling, and compared them to 24 healthy age- and gender-matched controls. In chapter 1, I provide a research background and literature review. Chapter 2 describes the neuropsychological assessments which demonstrated trait-related deficits in working memory with slower processing speed representing an endophenotype. Chapter 3 describes the implicit/ explicit facial emotion processing task performed during event-related functional MRI (erfMRI). Pairwise comparisons demonstrated implicit processing was associated with increases in lingual gyrus and insula activations and explicit processing elicited reduced fusiform activations in patients compared with controls. Increased posterior cingulate activations and reductions in putamen and cerebellar activity were found in siblings compared to controls, and reductions in parietal activations were noted in siblings compared to their ill relatives. These findings suggest over-activations in regions involved in facial expression recognition and attentional shifting (lingual and insula respectively) and deactivations in a region important for the perception and recognition of faces (fusiform) represent correlates of disease expression. Additionally regional deactivations associated with category learning and attentional processing (parietal, putamen and cerebellar) and increased activations in a region involved in emotional salience (posterior cingulate) may represent adaptive responses associated with resilience. Chapter 4 describes an instrumental reward-learning task performed during erfMRI. Data were analysed at whole brain level and using a priori region of interest analyses in ventral striatum/midbrain and prefrontal cortex (PFC). Results included increased ventral striatum activation in association with the difference between observed and expected rewarding outcomes (the prediction error (PE)) in patients compared to controls. Decreased prefrontal activations were seen in the patient and sibling groups compared to controls in association with the learning of the value of the conditioned stimulus. These findings suggest that i) PE associated circuitry (striatal) overactivation, and ii) prefrontal deactivations underlie the genetic vulnerability to BD.en
dc.contributor.sponsorWellcome Trusten
dc.language.isoenen
dc.publisherThe University of Edinburghen
dc.relation.hasversionMcIntosh AM, Whalley HC, McKirdy J, Hall J, Sussmann JE, Shankar P, Johnstone EC, Lawrie SM. Prefrontal function and activation in bipolar disorder and schizophrenia. The American journal of psychiatry 165, 378–84 (2008).en
dc.relation.hasversionSprooten E, Sussmann JE, Clugston A, Peel A, McKirdy J, Moorhead TW, Anderson S, Shand AJ, Giles S, Bastin ME, Hall J, Johnstone EC, Lawrie SM, McIntosh AM. White matter integrity in individuals at high genetic risk of bipolar disorder. Biol. Psychiatry 70, 350–6 (2011).en
dc.relation.hasversionWhalley HC, Sussmann JE, Chakirova G, Mukerjee P, Peel A, McKirdy J, Hall J, Johnstone EC, Lawrie SM, McIntosh AM. The Neural Basis of Familial Risk and Temperamental Variation in Individuals at High Risk of Bipolar Disorder. Biological Psychiatry 70, 343–349 (2011).en
dc.relation.hasversionWhalley HC, Sprooten E, Hackett S, Hall L, Blackwood DH, Glahn DC, Bastin M, Hall J, Lawrie SM, Sussmann JE, McIntosh AM. Polygenic risk and white matter integrity in individuals at high risk of mood disorder. Biol. Psychiatry 74, 280–6 (2013a).en
dc.relation.hasversionWhalley HC, Sussmann JE, Romaniuk L, Stewart T, Papmeyer M, Sprooten E, Hackett S, Hall J, Lawrie SM, McIntosh AM. Prediction of depression in individuals at high familial risk of mood disorders using functional magnetic resonance imaging. PloS one 8, e57357 (2013b).en
dc.subjectneuroimagingen
dc.subjectBipolar Affective Disorderen
dc.subjectemotion processingen
dc.subjectrewarden
dc.subjectreinforcement learningen
dc.titleNeural basis of genetic vulnerability to bipolar disorderen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD Doctor of Philosophyen


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