Attenuation of the Neural Response to Sad Faces in Major Depressionby Antidepressant Treatment

Background

Depression is associated with interpersonal difficulties related to abnormalities in affective facial processing.

Objectives

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.

Design

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.

Setting

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 satisfyingDSM-IVcriteria for unipolar major depressive disorder by age, sex, and IQ with 19 healthy volunteers.

Intervention

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 inference.

Results

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.

Conclusions

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.