Faculty Bibliography

OBJECTIVES/OBJECTIVE:Convergent evidence supports limbic, anterior paralimbic, and prefrontal cortex (PFC) abnormalities in emotional processing in bipolar disorder (BD) and suggests that some abnormalities are mood-state dependent and others persist into euthymia. However, few studies have assessed elevated, depressed, and euthymic mood states while individuals processed emotional stimuli of varying valence to investigate trait- and state-related neural system responses. Here, regional brain responses to positive, negative, and neutral emotional stimuli were assessed in individuals with BD during elevated, depressed, and euthymic mood states. METHODS:One hundred and thirty-four subjects participated in functional magnetic resonance imaging scanning while processing faces depicting happy, fearful, and neutral expressions: 76 with BD (18 in elevated mood states, 19 depressed, 39 euthymic) and 58 healthy comparison (HC) individuals. Analyses were performed for BD trait- and mood state-related features. RESULTS:Ventral anterior cingulate cortex (VACC), orbitofrontal cortex (OFC), and ventral striatum responses to happy and neutral faces were decreased in the BD group, compared to the HC group, and were not influenced by mood state. Elevated mood states were associated with decreased right rostral PFC activation to fearful and neutral faces, and depression was associated with increased left OFC activation to fearful faces. CONCLUSIONS:The findings suggest that abnormal VACC, OFC, and ventral striatum responses to happy and neutral stimuli are trait features of BD. Acute mood states may be associated with additional lateralized abnormalities of diminished right rostral PFC responses to fearful and neutral stimuli in elevated states and increased left OFC responses to fearful stimuli in depressed states.

Functional neuroimaging techniques have been important research tools in the study of bipolar disorder (BPD). These methods provide measures of regional brain functioning that reflect the mental state at the time of scanning and have helped to elucidate both state and trait features of BPD. This chapter will review converging functional neuroimaging evidence implicating state and trait dysfunction in a ventral prefrontal cortex-amygdala neural system in BPD. Emerging evidence that suggests a developmental progression in dysfunction in this neural system over the course of adolescence will be considered. Finally, new research approaches that have begun to reveal the contribution of specific genetic mechanisms to regional dysfunction in the disorder, potential salutary effects of medications, and structure-function relationships will be discussed.