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A Functional Magnetic Resonance Imaging Study of Bipolar Disorder
State- and Trait-Related Dysfunction in Ventral Prefrontal Cortices
Hilary P. Blumberg, MD;
Hoi-Chung Leung, PhD;
Pawel Skudlarski, PhD;
Cheryl M. Lacadie, BS;
Carolyn A. Fredericks;
Brent C. Harris;
Dennis S. Charney, MD;
John C. Gore, PhD;
John H. Krystal, MD;
Bradley S. Peterson, MD
Arch Gen Psychiatry. 2003;60:601-609.
Background Abnormalities in prefrontal and anterior cingulate cortices are implicated in disturbances of attention, cognition, and impulse regulation in bipolar disorder. Acute episodes have been associated with dysfunction in these brain regions, and more enduring trait-related dysfunction has been implicated by volumetric and cellular abnormalities in these regions. The relative contributions of prefrontal regions to state and trait disturbances in bipolar disorder, however, have not been defined. We sought to characterize state- and trait-related functional impairment in frontal systems in bipolar disorder.
Methods Thirty-six individuals with bipolar disorder I (11 with elevated, 10 with depressed, and 15 with euthymic mood states) and 20 healthy control subjects matched for handedness and sex participated in an event-related functional magnetic resonance imaging study of the color-word Stroop to determine mean percentage of regional task-related signal change.
Results Signal increased during the Stroop task similarly across diagnostic groups in a distribution that included dorsal anterior cingulate and prefrontal cortices, consistent with previously reported activations in this task. Signal changes associated with specific mood states in bipolar disorder were detected in ventral prefrontal cortex, with a blunted increase in signal on the right side in the elevated mood group (P = .005) and an exaggerated increase in signal on the left side in the depressed group (P = .02) compared with the euthymic group. Patients (vs healthy controls) demonstrated blunted activation in a spatially distinct, rostral region of left ventral prefrontal cortex that was independent of mood state (P<.005).
Conclusions Bipolar disorder is associated with a trait abnormality in left ventral prefrontal cortex. Additional ventral prefrontal abnormalities may be associated with specific acute mood states. The hemispheric laterality of the abnormality and the directions of signal change may relate to the valence of the mood episode.
From the Departments of Psychiatry (Drs Blumberg and Krystal, Ms Fredericks, and Mr Harris) and Diagnostic Radiology (Drs Leung and Skudlarski and Ms Lacadie), Yale University School of Medicine, New Haven, Conn; Department of Psychiatry (Drs Blumberg, Leung, and Krystal), Veterans Affairs Connecticut Healthcare System, West Haven; Department of Psychology, State University of New York, Stony Brook (Dr Leung); the Mood and Anxiety Disorders Research Program, National Institute of Mental Health, Bethesda, Md (Dr Charney); Department of Radiology, Vanderbilt University Medical Center, Nashville, Tenn (Dr Gore); and the Department of Psychiatry, Columbia College of Physicians and Surgeons, and the New York State Psychiatric Institute, New York (Dr Peterson).
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