Ventromedial prefrontal cortex and amygdala dysfunction during an anger induction positron emission tomography study in patients with major depressive disorder with anger attacks.
BACKGROUND
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.


METHODS
We used positron emission tomography, psychophysiologic measures, and autobiographical narrative scripts in the context of an anger induction paradigm.


METHODS
Academic medical center.


METHODS
Thirty individuals, evenly divided among the 3 study groups.


METHODS
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.


METHODS
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.


CONCLUSIONS
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.
Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA. ddougherty@partners.org
Darin D
DD
Dougherty
Scott L
SL
Rauch
Thilo
T
Deckersbach
Carl
C
Marci
Rebecca
R
Loh
Lisa M
LM
Shin
Nathaniel M
NM
Alpert
Alan J
AJ
Fischman
Maurizio
M
Fava
D000328:Adult; D000679:Amygdala / Q000098:blood supply / Q000000981:diagnostic imaging / Q000503:physiopathology*; D000786:Anger / Q000502:physiology*; D001931:Brain Mapping; D002421:Caudate Nucleus / Q000503:physiopathology; D003866:Depressive Disorder / Q000000981:diagnostic imaging / Q000503:physiopathology*; D003937:Diagnosis, Differential; D004644:Emotions / Q000502:physiology; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D008016:Life Change Events; D008297:Male; D017397:Prefrontal Cortex / Q000098:blood supply / Q000000981:diagnostic imaging / Q000503:physiopathology*; D011603:Psychophysiology / Q000379:methods; D012039:Regional Blood Flow / Q000502:physiology; D012107:Research Design; D013788:Thalamus / Q000000981:diagnostic imaging / Q000503:physiopathology; D014055:Tomography, Emission-Computed; D014705:Verbal Behavior / Q000502:physiology