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Ventromedial Prefrontal Cortex and Amygdala Dysfunction During an Anger Induction Positron Emission Tomography Study in Patients With Major Depressive Disorder With Anger Attacks
Darin D. Dougherty, MD, MSc;
Scott L. Rauch, MD;
Thilo Deckersbach, PhD;
Carl Marci, MD;
Rebecca Loh, BS;
Lisa M. Shin, PhD;
Nathaniel M. Alpert, PhD;
Alan J. Fischman, MD, PhD;
Maurizio Fava, MD
Arch Gen Psychiatry. 2004;61:795-804.
Context Although a variety of functional neuroimaging studies have used emotion induction paradigms to investigate the neural basis of anger in control subjects, no functional neuroimaging studies using anger induction have been conducted in patient populations.
Objective To study the neural basis of anger in unmedicated patients with major depressive disorder with anger attacks (MDD + A), unmedicated patients with MDD without anger attacks (MDD – A), and controls.
Design We used positron emission tomography, psychophysiologic measures, and autobiographical narrative scripts in the context of an anger induction paradigm.
Setting Academic medical center.
Participants Thirty individuals, evenly divided among the 3 study groups.
Interventions In separate conditions, participants were exposed to anger and neutral autobiographical scripts during the positron emission tomography study. Subjective self-report and psychophysiologic data were also collected.
Main Outcome Measures Voxelwise methods were used for analyses of regional cerebral blood flow changes for the anger vs neutral contrast within and between groups.
Results Controls showed significantly (P<.001) greater regional cerebral blood flow increases in the left ventromedial prefrontal cortex during anger induction than patients with MDD + A, whereas these differences were not present in other between-group analyses. Also, in controls, an inverse relationship was demonstrated between regional cerebral blood flow changes during anger induction in the left ventromedial prefrontal cortex and left amygdala, whereas in patients with MDD + A there was a positive correlation between these brain regions during anger induction. There was no significant relationship between these brain regions during anger induction in patients with MDD – A.
Conclusion These results suggest a pathophysiology of MDD + A that is distinct from that of MDD – A and that may be responsible for the unique clinical presentation of patients with MDD + A.
From the Departments of Psychiatry (Drs Dougherty, Rauch, Deckersbach, Marci, Shin, and Fava and Ms Loh) and Radiology (Drs Dougherty, Rauch, Alpert, and Fischman), Massachusetts General Hospital and Harvard Medical School, Boston, Mass; and the Department of Psychology, Tufts University, Medford, Mass (Dr Shin).
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