Skip to main content Accessibility help

Impaired subjective well-being in schizophrenia is associated with reduced anterior cingulate activity during reward processing

  • J. Gilleen (a1), S. S. Shergill (a1) and S. Kapur (a1)



Patients with schizophrenia have substantially reduced subjective well-being (SW) compared to healthy individuals. It has been suggested that diminished SW may be related to deficits in the neural processing of reward but this has not been shown directly. We hypothesized that, in schizophrenia, lower SW would be associated with attenuated reward-related activation in the reward network.


Twenty patients with schizophrenia with a range of SW underwent a functional magnetic resonance imaging (fMRI) reward task. The brain activity underlying reward anticipation and outcome in schizophrenia was examined and compared to that of 12 healthy participants using a full factorial analysis. Region of interest (ROI) analyses of areas within the reward network and whole-brain analyses were conducted to reveal neural correlates of SW.


Reward-related neural activity in schizophrenia was not significantly different from that of healthy participants; however, the patients with schizophrenia showed significantly diminished SW. Both ROI and whole-brain analyses confirmed that SW scores in the patients correlated significantly with activity, specifically in the dorsal anterior cingulate cortex (dACC), during both reward anticipation and reward outcome. This association was not seen in the healthy participants.


In patients with schizophrenia, reduced activation of the dACC during multiple aspects of reward processing is associated with lower SW. As the dACC has been widely linked to coupling of reward and action, and the link to SW is apparent over anticipation and outcome, these findings suggest that SW deficits in schizophrenia may be attributable to reduced integration of environmental rewarding cues, motivated behaviour and reward outcome.


Corresponding author

* Address for correspondence: J. Gilleen, Ph.D., Department of Psychosis Studies, Institute of Psychiatry, King's College London, PO Box 63, De Crespigny Park, Denmark Hill, London SE5 8AF, UK. (Email:


Hide All
Abler, B, Erk, S, Walter, H (2007). Human reward system activation is modulated by a single dose of olanzapine in healthy subjects in an event-related, double-blind, placebo-controlled fMRI study. Psychopharmacology 191, 823833.
Abler, B, Kammerer, H, Frasch, K, Spitzer, M, Walter, H (2008). Altered reward processing in schizophrenic patients treated with olanzapine. Schizophrenia Research 98 (Suppl.), 116.
Averbeck, B, Evans, S, Chouhan, V, Bristow, E, Shergill, SS (2011). Probabilistic learning and inference in schizophrenia. Schizophrenia Research 127, 115122.
Barnes, TR (1989). A rating scale for drug-induced akathisia. British Journal of Psychiatry 154, 672676.
Beck, AT, Steer, RA, Ball, R, Ranieri, W (1996). Comparison of Beck Depression Inventories -IA and -II in psychiatric outpatients. Journal of Personality Assessment 67, 588597.
Bench, CJ, Friston, KJ, Brown, RG, Scott, LC, Frackowiak, RS, Dolan, RJ (1992). The anatomy of melancholia – focal abnormalities of cerebral blood flow in major depression. Psychological Medicine 22, 607615.
Chouinard, G, Ross-Chouinard, A, Annable, L, Jones, B (1980). The extrapyramidal symptom rating scale. Canadian Journal of Neurological Sciences 7, 233239.
Critchley, HD, Mathias, CJ, Dolan, RJ (2001). Neural activity in the human brain relating to uncertainty and arousal during anticipation. Neuron 29, 537545.
da Silva Alves, D, Schmitz, N, Figee, M, Abeling, N, Hasler, G, van der Meer, J, Nederveen, A, de Haan, L, Linszen, D, van Amelsvoort, T (2010). Dopaminergic modulation of the human reward system: a placebo-controlled dopamine depletion fMRI study. Journal of Psychopharmacology 25, 538549.
de Haan, L, Lavalaye, J, Linszen, D, Dingemans, PM, Booij, J (2000). Subjective experience and striatal dopamine D(2) receptor occupancy in patients with schizophrenia stabilized by olanzapine or risperidone. American Journal of Psychiatry 157, 10191020.
Dolan, RJ, Fletcher, P, Frith, CD, Friston, KJ, Frackowiak, RS, Grasby, PM (1995). Dopaminergic modulation of impaired cognitive activation in the anterior cingulate cortex in schizophrenia. Nature 378, 180182.
Friston, KJ, Fletcher, P, Josephs, O, Holmes, A, Rugg, MD, Turner, R (1998). Event-related fMRI: characterizing differential responses. NeuroImage 17, 3040.
Gard, DE, Kring, AM, Gard, MG, Horan, WP, Green, MF (2007). Anhedonia in schizophrenia: distinctions between anticipatory and consummatory pleasure. Schizophrenia Research 93, 253260.
Haber, SN, Knutson, B (2010). The reward circuit: linking primate anatomy and human imaging. Neuropsychopharmacology 35, 426.
Harvey, PO, Pruessner, J, Czechowska, Y, Lepage, M (2007). Individual differences in trait anhedonia: a structural and functional magnetic resonance imaging study in non-clinical subjects. Molecular Psychiatry 12, 767775.
Juckel, G, Schlagenhauf, F, Koslowski, M, Filonov, D, Wustenberg, T, Villringer, A, Knutson, B, Kienast, T, Gallinat, J, Wrase, J, Heinz, A (2006). Dysfunction of ventral striatal reward prediction in schizophrenic patients treated with typical, not atypical, neuroleptics. Psychopharmacology 187, 222228.
Karow, A, Czekalla, J, Dittmann, RW, Schacht, A, Wagner, T, Lambert, M, Schimmelmann, BG, Naber, D (2007). Association of subjective well-being, symptoms, and side effects with compliance after 12 months of treatment in schizophrenia. Journal of Clinical Psychiatry 68, 7580.
Karow, A, Naber, D (2002). Subjective well-being and quality of life under atypical antipsychotic treatment. Psychopharmacology 162, 310.
Kay, SR, Fiszbein, A, Opler, LA (1987). The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261276.
Keedwell, PA, Andrew, C, Williams, SCR, Brammer, MJ, Phillips, ML (2005). The neural correlates of anhedonia in major depressive disorder. Biological Psychiatry 58, 843853.
Kirsch, P, Schienle, A, Stark, R, Sammer, G, Blecker, C, Walter, B, Ott, U, Burkart, J, Vaitl, D (2003). Anticipation of reward in a nonaversive differential conditioning paradigm and the brain reward system: an event-related fMRI study. NeuroImage 20, 10861095.
Knutson, B, Adams, CM, Fong, GW, Hommer, D (2001). Anticipation of increasing monetary reward selectively recruits nucleus accumbens. Journal of Neuroscience 21, 159.
Knutson, B, Bhanji, JP, Cooney, RE, Atlas, LY, Gotlib, IH (2008). Neural responses to monetary incentives in major depression. Biological Psychiatry 63, 686692.
Knutson, B, Gibbs, SEB (2007). Linking nucleus accumbens dopamine and blood oxygenation. Psychopharmacology 191, 812822.
Lambert, M, Naber, D (2004). Current issues in schizophrenia: overview of patient acceptability, functioning capacity and quality of life. CNS Drugs 18 (Suppl. 2), 517.
Larisch, R, Klimke, A, Vosberg, H, Loffler, S, Gaebel, W, Muller-Gartner, HW (1997). In vivo evidence for the involvement of dopamine-D2 receptors in striatum and anterior cingulate gyrus in major depression. NeuroImage 5 (Pt 1), 251260.
Lataster, J, van Os, J, de Haan, L, Thewissen, B, Bak, M, Lataster, T, Lardinois, M, Delespaul, PA, Myin-Germeys, I (2010). Emotional experience and estimates of D2 receptor occupancy in psychotic patients treated with haloperidol, risperidone, or olanzapine: an experience sampling study. Journal of Clinical Psychiatry 72, 13971404.
Maldjian, JA, Laurienti, PJ, Kraft, RA, Burdette, JH (2003). An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. NeuroImage 19, 12331239.
Mawlawi, O, Martinez, D, Slifstein, M, Broft, A, Chatterjee, R, Hwang, DR, Huang, Y, Simpson, N, Ngo, K, Van Heertum, R, Laruelle, M (2001). Imaging human mesolimbic dopamine transmission with positron emission tomography: I. Accuracy and precision of D(2) receptor parameter measurements in ventral striatum. Journal of Cerebral Blood Flow and Metabolism 21, 10341057.
Miller, DD, Andreasen, NC, O'Leary, DS, Rezai, K, Watkins, GL, Ponto, LL, Hichwa, RD (1997). Effect of antipsychotics on regional cerebral blood flow measured with positron emission tomography. Neuropsychopharmacology 17, 230240.
Mizrahi, R, Mamo, D, Rusjan, P, Graff, A, Houle, S, Kapur, S (2009). The relationship between subjective well-being and dopamine D2 receptors in patients treated with a dopamine partial agonist and full antagonist antipsychotics. International Journal of Neuropsychopharmacology 12, 715721.
Mizrahi, R, Rusjan, P, Agid, O, Graff, A, Mamo, DC, Zipursky, RB, Kapur, S (2007). Adverse subjective experience with antipsychotics and its relationship to striatal and extrastriatal D2 receptors: a PET study in schizophrenia. American Journal of Psychiatry 164, 630637.
Naber, D (1995). A self-rating to measure subjective effects of neuroleptic drugs, relationships to objective psychopathology, quality of life, compliance and other clinical variables. International Clinical Psychopharmacology 10 (Suppl. 3), 133138.
Naber, D, Karow, A, Lambert, M (2005). Subjective well-being under the neuroleptic treatment and its relevance for compliance. Acta Psychiatrica Scandinavica. Supplementum 427, 2934.
Naber, D, Moritz, S, Lambert, M, Pajonk, FG, Holzbach, R, Mass, R, Andresen, B (2001). Improvement of schizophrenic patients’ subjective well-being under atypical antipsychotic drugs. Schizophrenia Research 50, 7988.
Nelson, HE, Willison, JR (1991). The Revised National Adult Reading Test (NART): Test Manual. NFER-Nelson: Windsor.
Ochsner, KN, Kosslyn, SM, Cosgrove, GR, Cassem, EH, Price, BH, Nierenberg, AA, Rauch, SL (2001). Deficits in visual cognition and attention following bilateral anterior cingulotomy. Neuropsychologia 39, 219230.
Quintana, J, Wong, T, Ortiz-Portillo, E, Marder, SR, Mazziotta, JC (2004). Anterior cingulated dysfunction during choice anticipation in schizophrenia. Psychiatry Research 132, 117130.
Schlagenhauf, F, Juckel, G, Koslowski, M, Kahnt, T, Knutson, B, Dembler, T, Kienast, T, Gallinat, J, Wrase, J, Heinz, A (2007). Reward system activation in schizophrenic patients switched from typical neuroleptics to olanzapine. Psychopharmacology 196, 673684.
Schlagenhauf, F, Sterzer, P, Schmack, K, Ballmaier, M, Rapp, M, Wrase, J, Juckel, G, Gallinat, J, Heinz, A (2009). Reward feedback alterations in unmedicated schizophrenia patients: relevance for delusions. Biological Psychiatry 65, 10321039.
Schott, BH, Minuzzi, L, Krebs, RM, Elmenhorst, D, Lang, M, Winz, OH, Seidenbecher, CI, Coenen, HH, Heinze, HJ, Zilles, K, Düzel, E, Bauer, A (2008). Mesolimbic functional magnetic resonance imaging activations during reward anticipation correlate with reward-related ventral striatal dopamine release. Journal of Neuroscience 28, 1431114319.
Simpson, GM, Angus, JW (1970). A rating scale for extrapyramidal side effects. Acta Psychiatrica Scandinavica. Supplementum 212, 1119.
Voruganti, L, Awad, AG (2004). Neuroleptic dysphoria: towards a new synthesis. Psychopharmacology 171, 121132.
Voruganti, L, Slomka, P, Zabel, P, Costa, G, So, A, Mattar, A, Awad, G (2001). Subjective effects of AMPT-induced dopamine depletion in schizophrenia: correlation between dysphoric responses and striatal D(2) binding ratios on SPECT imaging. Neuropsychopharmacology 25, 642650.
Vothknecht, S, Meijer, C, Zwinderman, A, Kikkert, M, Dekker, J, van Beveren, N, Schoevers, R, de Haan, L; for GROUP (Genetic Risk and Outcome of Psychosis) (2012). Psychometric evaluation of the Subjective Well-being Under Neuroleptic Treatment Scale (SWN) in patients with schizophrenia, their relatives and controls. Psychiatry Research 206, 6267.
Williams, ZM, Bush, G, Rauch, SL, Cosgrove, GR, Eskandar, EN (2004). Human anterior cingulated neurons and the integration of monetary reward with motor responses. Nature Neuroscience 7, 13701375.



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed