Psychological Medicine

Original Articles

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

L. R. Demenescua1a2, R. Renkena1, R. Kortekaasa1, M.-J. van Tola3, J. B. C. Marsmana4, M. A. van Buchema5, N. J. A. van der Weea3, D. J. Veltmana6, J. A. den Boera7 and A. Alemana1a8 c1

a1 Neuroimaging Center, Department of Neuroscience, University Medical Center Groningen, University of Groningen, The Netherlands

a2 Department of Psychiatry and Psychotherapy, RWTH Aachen University, Germany

a3 Department of Psychiatry and Leiden Institute for Brain and Cognition, Leiden University Medical Center, The Netherlands

a4 Laboratory of Experimental Ophthalmology and BCN Neuroimaging Center, University Medical Center Groningen, The Netherlands

a5 Department of Radiology and Leiden Institute for Brain and Cognition, Leiden University Medical Center, The Netherlands

a6 Department of Psychiatry, VU University Medical Center Amsterdam and Academic Medical Center Amsterdam, The Netherlands

a7 Department of Psychiatry, University Medical Center Groningen, The Netherlands

a8 Department of Psychology, University of Groningen, The Netherlands


Background 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.

Method 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.

Results 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.

Conclusions 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.

(Received October 21 2010)

(Revised March 21 2011)

(Accepted March 23 2011)

(Online publication May 06 2011)


c1 Address for correspondence: Prof. Dr. A. Aleman, BCN Neuroimaging Center, University Medical Center Groningen, A. Deusinglaan 2, 9713 AW, Groningen, The Netherlands. (Email: