Date of Award

January 2012

Document Type


Degree Name

Medical Doctor (MD)



First Advisor

Hilary Blumberg

Subject Area(s)



Bipolar Disorder (BD) is a psychiatric disorder with high associated rates of morbidity and mortality. Converging evidence from neuroimaging studies supports dysfunction in an anterior paralimbic cortex-amygdala neural system, particularly in regions of the ventral prefrontal cortex (PFC). Research has implicated abnormalities that are mood state dependent, and others that persist in euthymia implicating them as trait features of the disorder. However, few studies of BD have been designed to systematically assess subjects with BD in elevated, depressed, and euthymic mood states in comparison to healthy subjects. We performed functional magnetic resonance imaging scanning of one hundred and thirty-four subjects while they processed faces depicting happy, fearful, and neutral expressions: 76 with BD (18 in an elevated mood state, 19 depressed and 39 euthymic) and 58 healthy comparison (HC) individuals. Analyses were performed for BD trait- and mood-state-related features. Ventral anterior cingulate cortex (VACC), orbitofrontal cortex (OFC) and ventral striatum responses to happy and neutral faces were decreased in the overall BD group, compared to the HC group. These findings did not differ across the three mood states. Elevated mood states were associated with additional right rostral PFC activation decreases to fearful and neutral faces, and depressed mood states were associated with left ventrolateral OFC activation increases to fearful faces. These results support decreased activity in VACC, OFC, and ventral striatum as a trait feature of BD, and that acute mood states are associated with additional lateralized prefrontal abnormalities. This investigation of state and trait features of BD adds to the understanding of the neural system involved in vulnerability to, and function in, acute mood states, which may aide the development of new treatments for BD targeted to specific mood states or designed to better address the vulnerability to mood cycling.


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