Attenuation of the neural response to sad faces in major depression by antidepressant treatment: a prospective, event-related functional magnetic resonance imaging study.
BACKGROUND
Depression is associated with interpersonal difficulties related to abnormalities in affective facial processing.


OBJECTIVE
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.


METHODS
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.


METHODS
Participants were recruited by advertisement from the local population; depressed subjects were treated as outpatients.


METHODS
We matched 19 medication-free, acutely symptomatic patients satisfying DSM-IV criteria 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.


METHODS
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 x 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.
Fu
Cynthia H Y
CH
Institute of Psychiatry, King's College London, London, England.
Williams
Steven C R
SC
Cleare
Anthony J
AJ
Brammer
Michael J
MJ
Walsh
Nicholas D
ND
Kim
Jieun
J
Andrew
Chris M
CM
Pich
Emilio Merlo
EM
Williams
Pauline M
PM
Reed
Laurence J
LJ
Mitterschiffthaler
Martina T
MT
Suckling
John
J
Bullmore
Edward T
ET
D000339:Affect / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D001931:Brain Mapping / Q000379:methods; D003866:Depressive Disorder / Q000175:diagnosis* / Q000188:drug therapy* / Q000523:psychology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D005149:Facial Expression; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008032:Limbic System / Q000187:drug effects / Q000502:physiology; D008279:Magnetic Resonance Imaging / Q000379:methods* / Q000706:statistics & numerical data; D019579:Neocortex / Q000187:drug effects / Q000502:physiology; D011446:Prospective Studies; D012044:Regression Analysis; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014796:Visual Perception / Q000187:drug effects / Q000502:physiology*
D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors