Psychological Medicine

Original Articles

Neural correlates of ‘pessimistic’ attitude in depression

U. Herwiga1a2 c1, A. B. Brühla1, T. Kaffenbergera1a2, T. Baumgartnera3a4, H. Boekera1 and L. Jänckea3

a1 Psychiatric University Hospital Zürich, Switzerland

a2 Department of Psychiatry, University of Ulm, Germany

a3 Department of Neuropsychology, University of Zürich, Switzerland

a4 Institute for Empirical Research in Economics, University of Zürich, Switzerland


Background Preparing for potentially threatening events in the future is essential for survival. Anticipating the future to be unpleasant is also a cognitive key feature of depression. We hypothesized that ‘pessimism’-related emotion processing would characterize brain activity in major depression.

Method During functional magnetic resonance imaging, depressed patients and a healthy control group were cued to expect and then perceive pictures of known emotional valences – pleasant, unpleasant and neutral – and stimuli of unknown valence that could have been either pleasant or unpleasant. Brain activation associated with the ‘unknown’ expectation was compared with the ‘known’ expectation conditions.

Results While anticipating pictures of unknown valence, activation patterns in depressed patients within the medial and dorsolateral prefrontal areas, inferior frontal gyrus, insula and medial thalamus were similar to activations associated with expecting unpleasant pictures, but not with expecting positive pictures. The activity within a majority of these areas correlated with the depression scores. Differences between healthy and depressed persons were found particularly for medial and dorsolateral prefrontal and insular activations.

Conclusions Brain activation in depression during expecting events of unknown emotional valence was comparable with activation while expecting certainly negative, but not positive events. This neurobiological finding is consistent with cognitive models supposing that depressed patients develop a ‘pessimistic’ attitude towards events with an unknown emotional meaning. Thereby, particularly the role of brain areas associated with the processing of cognitive and executive control and of the internal state is emphasized in contributing to major depression.

(Received November 12 2008)

(Revised May 26 2009)

(Accepted July 16 2009)

(Online publication September 07 2009)


c1 Address for correspondence: U. Herwig, M.D., M.A., Psychiatric University Hospital, University of Zürich, Lenggstrasse 31, CH – 8032 Zürich, Switzerland. (Email: