Skip to main content
    • Aa
    • Aa

Neural correlates of ‘pessimistic’ attitude in depression

  • U. Herwig (a1) (a2), A. B. Brühl (a1), T. Kaffenberger (a1) (a2), T. Baumgartner (a3) (a4), H. Boeker (a1) and L. Jäncke (a3)...

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.


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.


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.


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.

Corresponding author
*Address for correspondence: U. Herwig, M.D., M.A., Psychiatric University Hospital, University of Zürich, Lenggstrasse 31, CH – 8032Zürich, Switzerland. (Email:
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

B Abler , S Erk , U Herwig , H Walter (2006). Anticipation of aversive stimuli activates extended amygdala in unipolar depression. Journal of Psychiatric Research 41, 511522.

AK Anderson , K Christoff , I Stappen , D Panitz , DG Ghahremani , G Glover , JD Gabrieli , N Sobel (2003). Dissociated neural representations of intensity and valence in human olfaction. Nature Neuroscience 6, 196202.

M Annett (1967). The binomial distribution of right, mixed and left handedness. Quarterly Journal of Experimental Psychology 19, 327333.

LR Baxter Jr, JM Schwartz , ME Phelps , JC Mazziotta , BH Guze , CE Selin , RH Gerner , RM Sumida (1989). Reduction of prefrontal cortex glucose metabolism common to three types of depression. Archives of General Psychiatry 46, 243250.

AT Beck (1967). Depression: Clinical, Experimental and Theoretical Aspects. Harper & Row: New York.

AT Beck , CH Ward , M Mendelson , J Mock , J Erbaugh (1961). An inventory for measuring depression. Archives of General Psychiatry 4, 561571.

F Bermpohl , A Pascual-Leone , A Amedi , LB Merabet , F Fregni , N Gaab , D Alsop , G Schlaug , G Northoff (2006). Dissociable networks for the expectancy and perception of emotional stimuli in the human brain. NeuroImage 30, 588600.

AJ Calder , AD Lawrence , AW Young (2001). Neuropsychology of fear and loathing. Nature Reviews Neuroscience 2, 352363.

CS Carter , AM Macdonald , M Botvinick , LL Ross , VA Stenger , D Noll , JD Cohen (2000). Parsing executive processes: strategic vs. evaluative functions of the anterior cingulate cortex. Proceedings of the National Academy of Sciences of the USA 97, 19441948.

PS Churchland (2002). Self-representation in nervous systems. Science 296, 308310.

AD Craig (2002). How do you feel? Interoception: the sense of the physiological condition of the body. Nature Reviews Neuroscience 3, 655666.

HD Critchley , S Wiens , P Rotshtein , A Ohman , RJ Dolan (2004). Neural systems supporting interoceptive awareness. Nature Neuroscience 7, 189195.

AR Damasio , TJ Grabowski , A Bechara , H Damasio , LL Ponto , J Parvizi , RD Hichwa (2000). Subcortical and cortical brain activity during the feeling of self-generated emotions. Nature Neuroscience 3, 10491056.

U Dannlowski , P Ohrmann , J Bauer , J Deckert , C Hohoff , H Kugel , V Arolt , W Heindel , A Kersting , BT Baune , T Suslow (2008). 5-HTTLPR biases amygdala activity in response to masked facial expressions in major depression. Neuropsychopharmacology 33, 418424.

RJ Davidson , W Irwin , MJ Anderle , NH Kalin (2003). The neural substrates of affective processing in depressed patients treated with venlafaxine. American Journal of Psychiatry 160, 6475.

RJ Davidson , D Pizzagalli , JB Nitschke , K Putnam (2002). Depression: perspectives from affective neuroscience. Annual Reviews of Psychology 53, 545574.

WC Drevets (2001). Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders. Current Opinions in Neurobiology 11, 240249.

S Erk , H Walter , B Abler (2008). Age-related physiological responses to emotion anticipation and exposure. Neuroreport 19, 447452.

CL Fales , DM Barch , MM Rundle , MA Mintun , AZ Snyder , JD Cohen , J Mathews , YI Sheline (2008). Altered emotional interference processing in affective and cognitive-control brain circuitry in major depression. Biological Psychiatry 63, 377384.

JM Fuster (2000). Executive frontal functions. Experimental Brain Research 133, 6670.

B Gibson , DM Sanbonmatsu (2004). Optimism, pessimism, and gambling: the downside of optimism. Personality and Social Psychology Bulletin 30, 149160.

DT Gilbert , TD Wilson (2007). Prospection: experiencing the future. Science 317, 13511354.

GH Glover (1999). Deconvolution of impulse response in event-related BOLD fMRI. NeuroImage 9, 416429.

S Grimm , J Beck , D Schuepbach , D Hell , P Boesiger , F Bermpohl , L Niehaus , H Boeker , G Northoff (2008). Imbalance between left and right dorsolateral prefrontal cortex in major depression is linked to negative emotional judgment: an fMRI study in severe major depressive disorder. Biological Psychiatry 63, 369376.

JJ Gross , OP John (2003). Individual differences in two emotion regulation processes: implications for affect, relationships, and well-being. Journal of Personality and Social Psychology 85, 348362.

M Hamilton (1960). A rating scale for depression. Journal of Neurology, Neurosurgery, and Psychiatry 23, 5662.

PO Harvey , P Fossati , JB Pochon , R Levy , G Lebastard , S Lehericy , JF Allilaire , B Dubois (2005). Cognitive control and brain resources in major depression: an fMRI study using the n-back task. NeuroImage 26, 860869.

L Heimer , GW Van Hoesen (2006). The limbic lobe and its output channels: implications for emotional functions and adaptive behaviour. Neuroscience and Biobehavioral Reviews 30, 126147.

U Herwig , T Baumgartner , T Kaffenberger , A Bruhl , M Kottlow , U Schreiter-Gasser , B Abler , L Jancke , M Rufer (2007 a). Modulation of anticipatory emotion and perception processing by cognitive control. NeuroImage 37, 652662.

U Herwig , T Kaffenberger , T Baumgartner , L Jancke (2007 b). Neural correlates of a ‘pessimistic’ attitude when anticipating events of unknown emotional valence. NeuroImage 34, 848858.

T Johnstone , CM van Reekum , HL Urry , NH Kalin , RJ Davidson (2007). Failure to regulate: counterproductive recruitment of top-down prefrontal-subcortical circuitry in major depression. Journal of Neuroscience 27, 88778884.

PA Keedwell , C Andrew , SC Williams , MJ Brammer , ML Phillips (2005). The neural correlates of anhedonia in major depressive disorder. Biological Psychiatry 58, 843853.

B Knutson , JP Bhanji , RE Cooney , LY Atlas , IH Gotlib (2008). Neural responses to monetary incentives in major depression. Biological Psychiatry 63, 686692.

PJ Lang (1995). The emotion probe. Studies of motivation and attention. American Psychologist 50, 372385.

SA Langenecker , SE Kennedy , LM Guidotti , EM Briceno , LS Own , T Hooven , EA Young , H Akil , DC Noll , JK Zubieta (2007). Frontal and limbic activation during inhibitory control predicts treatment response in major depressive disorder. Biological Psychiatry 62, 12721280.

A Lavender , E Watkins (2004). Rumination and future thinking in depression. British Journal of Clinical Psychology 43, 129142.

BT Lee , C Seong Whi , K Hyung Soo , BC Lee , IG Choi , IK Lyoo , BJ Ham (2007). The neural substrates of affective processing toward positive and negative affective pictures in patients with major depressive disorder. Progress in Neuropsychopharmacology and Biological Psychiatry 31, 14871492.

JM Leppanen (2006). Emotional information processing in mood disorders: a review of behavioral and neuroimaging findings. Current Opinions in Psychiatry 19, 3439.

HS Mayberg (2003). Positron emission tomography imaging in depression: a neural systems perspective. Neuroimaging Clinics of North America 13, 805815.

SM McClure , MK York , PR Montague (2004). The neural substrates of reward processing in humans: the modern role of fMRI. Neuroscientist 10, 260268.

SA Montgomery , M Åsberg (1979). A new depression scale designed to be sensitive to change. British Journal of Psychiatry 134, 382389.

RM Nesse (2000). Is depression an adaptation? Archives of General Psychiatry 57, 1420.

T Nichols , M Brett , J Andersson , T Wager , JB Poline (2005). Valid conjunction inference with the minimum statistic. NeuroImage 25, 653660.

JB Nitschke , I Sarinopoulos , KL Mackiewicz , HS Schaefer , RJ Davidson (2006). Functional neuroanatomy of aversion and its anticipation. NeuroImage 29, 106116.

JK Norem , N Cantor (1986). Defensive pessimism: harnessing anxiety as motivation. Journal of Personality and Social Psychology 51, 12081217.

G Northoff , F Bermpohl (2004). Cortical midline structures and the self. Trends in Cognitive Sciences 8, 102107.

J Panksepp (2006). Emotional endophenotypes in evolutionary psychiatry. Progress in Neuropsychopharmacology and Biological Psychiatry 30, 774784.

MP Paulus , JS Feinstein , G Castillo , AN Simmons , MB Stein (2005). Dose-dependent decrease of activation in bilateral amygdala and insula by lorazepam during emotion processing. Archives of General Psychiatry 62, 282288.

MP Paulus , MB Stein (2006). An insular view of anxiety. Biological Psychiatry 60, 383387.

L Pessoa (2008). On the relationship between emotion and cognition. Nature Reviews Neuroscience 9, 148158.

ML Phillips , WC Drevets , SL Rauch , R Lane (2003). Neurobiology of emotion perception II: Implications for major psychiatric disorders. Biological Psychiatry 54, 515528.

T Pyszczynski , K Holt , J Greenberg (1987). Depression, self-focused attention, and expectancies for positive and negative future life events for self and others. Journal of Personality and Social Psychology 52, 994–1001.

T Sharot , AM Riccardi , CM Raio , EA Phelps (2007). Neural mechanisms mediating optimism bias. Nature 450, 102105.

JA Shepperd , JK McNulty (2002). The affective consequences of expected and unexpected outcomes. Psychological Science 13, 8588.

GJ Siegle , W Thompson , CS Carter , SR Steinhauer , ME Thase (2007). Increased amygdala and decreased dorsolateral prefrontal BOLD responses in unipolar depression: related and independent features. Biological Psychiatry 61, 198209.

A Simmons , SC Matthews , MP Paulus , MB Stein (2008). Intolerance of uncertainty correlates with insula activation during affective ambiguity. Neuroscience Letters 430, 9297.

JC Soares , JJ Mann (1997). The anatomy of mood disorders – review of structural neuroimaging studies. Biological Psychiatry 41, 86–106.

O Sporns , CJ Honey , R Kotter (2007). Identification and classification of hubs in brain networks. PLoS ONE 2, e1049.

BA Vogt (2005). Pain and emotion interactions in subregions of the cingulate gyrus. Nature Reviews Neuroscience 6, 533544.

H Yamasaki , KS LaBar , G McCarthy (2002). Dissociable prefrontal brain systems for attention and emotion. Proceedings of the National Academy of Sciences of the USA 99, 1144711451.

R Yuste , JN MacLean , J Smith , A Lansner (2005). The cortex as a central pattern generator. Nature Reviews Neuroscience 6, 477483.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
Please enter your name
Please enter a valid email address
Who would you like to send this to? *


Type Description Title
Supplementary Materials

Herwig supplementary material

 Word (1.1 MB)
1.1 MB