Depression is associated with interpersonal difficulties related to
abnormalities in affective facial processing.
To map brain systems activated by sad facial affect processing in patients
with depression and to identify brain functional correlates of antidepressant
treatment and symptomatic response.
Two groups underwent scanning twice using functional magnetic resonance
imaging (fMRI) during an 8-week period. The event-related fMRI paradigm entailed
incidental affect recognition of facial stimuli morphed to express discriminable
intensities of sadness.
Participants were recruited by advertisement from the local population;
depressed subjects were treated as outpatients.
Patients and Other Participants
We matched 19 medication-free, acutely symptomatic patients satisfying DSM-IVcriteria for unipolar major depressive disorder
by age, sex, and IQ with 19 healthy volunteers.
After the baseline assessment, patients received fluoxetine hydrochloride,
20 mg/d, for 8 weeks.
Main Outcome Measures
Average activation (capacity) and differential response to variable
affective intensity (dynamic range) were estimated in each fMRI time series.
We used analysis of variance to identify brain regions that demonstrated a
main effect of group (depressed vs healthy subjects) and a group × time
interaction (attributable to antidepressant treatment). Change in brain activation
associated with reduction of depressive symptoms in the patient group was
identified by means of regression analysis. Permutation tests were used for
Over time, depressed subjects showed reduced capacity for activation
in the left amygdala, ventral striatum, and frontoparietal cortex and a negatively
correlated increase of dynamic range in the prefrontal cortex. Symptomatic
improvement was associated with reduction of dynamic range in the pregenual
cingulate cortex, ventral striatum, and cerebellum.
Antidepressant treatment reduces left limbic, subcortical, and neocortical
capacity for activation in depressed subjects and increases the dynamic range
of the left prefrontal cortex. Changes in anterior cingulate function associated
with symptomatic improvement indicate that fMRI may be a useful surrogate
marker of antidepressant treatment response.