 |
|
Attenuation of the Neural Response to Sad Faces in Major Depression by Antidepressant Treatment
A Prospective, Event-Related Functional Magnetic Resonance Imaging Study
Cynthia H. Y. Fu, MD, FRCPC;
Steven C. R. Williams, PhD;
Anthony J. Cleare, MRCPsych;
Michael J. Brammer, PhD;
Nicholas D. Walsh, BSc;
Jieun Kim, PhD;
Chris M. Andrew;
Emilio Merlo Pich, MD;
Pauline M. Williams, MD;
Laurence J. Reed, MRCPsych, PhD;
Martina T. Mitterschiffthaler, MSc;
John Suckling, PhD;
Edward T. Bullmore, MRCPsych, PhD
Arch Gen Psychiatry. 2004;61:877-889.
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 satisfying DSM-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 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.
From the Institute of Psychiatry, King's College London, London, England (Drs Fu, S. C. R. Williams, Cleare, Brammer, Kim, Reed, and Bullmore, Messrs Walsh and Andrew, and Ms Mitterschiffthaler); Clinical Pharmacology Discovery Medicine, Psychiatry Centre for Excellence in Drug Discovery (CEDD), GlaxoSmithKline SpA, Verona, Italy (Dr Pich); Discovery Medicine, Neurology CEDD, GlaxoSmithKline, Harlow, England (Dr P. M. Williams); and the Brain Mapping Unit, Department of Psychiatry, Addenbrooke's Hospital, University of Cambridge, Cambridge, England (Drs Suckling and Bullmore).
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Depressive State- and Disease-Related Alterations in Neural Responses to Affective and Executive Challenges in Geriatric Depression
Wang et al.
Am. J. Psychiatry 2008;165:863-871.
ABSTRACT
| FULL TEXT
Affective modulation of anterior cingulate cortex in young people at increased familial risk of depression
Mannie et al.
Br. J. Psychiatry 2008;192:356-361.
ABSTRACT
| FULL TEXT
Amygdala and Nucleus Accumbens Activation to Emotional Facial Expressions in Children and Adolescents at Risk for Major Depression
Monk et al.
Am. J. Psychiatry 2008;165:90-98.
ABSTRACT
| FULL TEXT
Orbitofrontal Cortex Function and Structure in Depression
DREVETS
Ann. N. Y. Acad. Sci. 2007;1121:499-527.
ABSTRACT
| FULL TEXT
A single dose of citalopram increases fear recognition in healthy subjects
Browning et al.
J Psychopharmacol 2007;21:684-690.
ABSTRACT
Human 5-HT Transporter Availability Predicts Amygdala Reactivity In Vivo
Rhodes et al.
J. Neurosci. 2007;27:9233-9237.
ABSTRACT
| FULL TEXT
Dynamic Organization of the Emotional Brain: Responsivity, Stability, and Instability
Williams and Gordon
Neuroscientist 2007;13:349-370.
ABSTRACT
Reciprocal Effects of Antidepressant Treatment on Activity and Connectivity of the Mood Regulating Circuit: An fMRI Study
Anand et al.
J. Neuropsychiatry Clin. Neurosi. 2007;19:274-282.
ABSTRACT
| FULL TEXT
Identifying Functional Neuroimaging Biomarkers of Bipolar Disorder: Toward DSM-V
Phillips and Vieta
Schizophr Bull 2007;33:893-904.
ABSTRACT
| FULL TEXT
Short-term antidepressant treatment and facial processing: Functional magnetic resonance imaging study
NORBURY et al.
Br. J. Psychiatry 2007;190:531-532.
ABSTRACT
| FULL TEXT
Neural Responses to Happy Facial Expressions in Major Depression Following Antidepressant Treatment
Fu et al.
Am. J. Psychiatry 2007;164:599-607.
ABSTRACT
| FULL TEXT
Abnormal Attention Modulation of Fear Circuit Function in Pediatric Generalized Anxiety Disorder
McClure et al.
Arch Gen Psychiatry 2007;64:97-106.
ABSTRACT
| FULL TEXT
Lack of Ventral Striatal Response to Positive Stimuli in Depressed Versus Normal Subjects
Epstein et al.
Am. J. Psychiatry 2006;163:1784-1790.
ABSTRACT
| FULL TEXT
Bipolar Disorder: Imaging State Versus Trait
Friedman et al.
J. Neuropsychiatry Clin. Neurosi. 2006;18:296-301.
FULL TEXT
Use of fMRI to Predict Recovery From Unipolar Depression With Cognitive Behavior Therapy
Siegle et al.
Am. J. Psychiatry 2006;163:735-738.
ABSTRACT
| FULL TEXT
Cholinergic challenge in Alzheimer patients and mild cognitive impairment differentially affects hippocampal activation--a pharmacological fMRI study
Goekoop et al.
Brain 2006;129:141-157.
ABSTRACT
| FULL TEXT
|
