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Neural correlates of perception of emotional facial expressions in out-patients with mild-to-moderate depression and anxiety. A multicenter fMRI study

Published online by Cambridge University Press:  06 May 2011

L. R. Demenescu
Neuroimaging Center, Department of Neuroscience, University Medical Center Groningen, University of Groningen, The Netherlands Department of Psychiatry and Psychotherapy, RWTH Aachen University, Germany
R. Renken
Neuroimaging Center, Department of Neuroscience, University Medical Center Groningen, University of Groningen, The Netherlands
R. Kortekaas
Neuroimaging Center, Department of Neuroscience, University Medical Center Groningen, University of Groningen, The Netherlands
M.-J. van Tol
Department of Psychiatry and Leiden Institute for Brain and Cognition, Leiden University Medical Center, The Netherlands
J. B. C. Marsman
Laboratory of Experimental Ophthalmology and BCN Neuroimaging Center, University Medical Center Groningen, The Netherlands
M. A. van Buchem
Department of Radiology and Leiden Institute for Brain and Cognition, Leiden University Medical Center, The Netherlands
N. J. A. van der Wee
Department of Psychiatry and Leiden Institute for Brain and Cognition, Leiden University Medical Center, The Netherlands
D. J. Veltman
Department of Psychiatry, VU University Medical Center Amsterdam and Academic Medical Center Amsterdam, The Netherlands
J. A. den Boer
Department of Psychiatry, University Medical Center Groningen, The Netherlands
A. Aleman*
Neuroimaging Center, Department of Neuroscience, University Medical Center Groningen, University of Groningen, The Netherlands Department of Psychology, University of Groningen, The Netherlands
*Address for correspondence: Prof. Dr. A. Aleman, BCN Neuroimaging Center, University Medical Center Groningen, A. Deusinglaan 2, 9713 AW, Groningen, The Netherlands. (Email:



Depression has been associated with limbic hyperactivation and frontal hypoactivation in response to negative facial stimuli. Anxiety disorders have also been associated with increased activation of emotional structures such as the amygdala and insula. This study examined to what extent activation of brain regions involved in perception of emotional faces is specific to depression and anxiety disorders in a large community-based sample of out-patients.


An event-related functional magnetic resonance imaging (fMRI) paradigm was used including angry, fearful, sad, happy and neutral facial expressions. One hundred and eighty-two out-patients (59 depressed, 57 anxiety and 66 co-morbid depression-anxiety) and 56 healthy controls selected from the Netherlands Study of Depression and Anxiety (NESDA) were included in the present study. Whole-brain analyses were conducted. The temporal profile of amygdala activation was also investigated.


Facial expressions activated the amygdala and fusiform gyrus in depressed patients with or without anxiety and in healthy controls, relative to scrambled faces, but this was less evident in patients with anxiety disorders. The response shape of the amygdala did not differ between groups. Depressed patients showed dorsolateral prefrontal cortex (PFC) hyperactivation in response to happy faces compared to healthy controls.


We suggest that stronger frontal activation to happy faces in depressed patients may reflect increased demands on effortful emotion regulation processes triggered by mood-incongruent stimuli. The lack of strong differences in neural activation to negative emotional faces, relative to healthy controls, may be characteristic of the mild-to-moderate severity of illness in this sample and may be indicative of a certain cognitive-emotional processing reserve.

Original Articles
Copyright © Cambridge University Press 2011

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