AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
PDF (807.9 KB)
Submit Manuscript AI Chat Paper
Show Outline
Show full outline
Hide outline
Show full outline
Hide outline
Review Article | Open Access

Anhedonia and its intervention in depressive adults: New developments based on Research Domain Criteria (RDoC) in mental illnesses

 Faculty of Psychology, Southwest University, Chongqing 400715, China
 The Affect Cognition and Regulation Laboratory, Institute of Brain and Psychological Sciences, Sichuan Normal University, Chengdu 610066, China
Show Author Information


Anhedonia, as one of the core symptoms of depression, is of great significance for the diagnosis and treatment of depression. Traditionally, anhedonia has been referred to as "loss of pleasure", while the recent research emphasizes that anhedonia is a complex and multidimensional construct based on reward processing impairment. Exploring different manifestations of anhedonia and developing the corresponding interventions have become indispensable in the current research of depression. Based on the positive valence system of the Research Domain Criteria (RDoC), this paper firstly demonstrates that the anhedonia of depressive adults are mainly characterized by the impairments in anticipatory pleasure, incentive motivation/effort, and reward learning based on subjective rating, behavioral, and neurophysiological evidences, while the existing evidences for the consummatory anhedonia of depression are inconsistent. Additionally, we introduce the vulnerability–stress model, as the mainstream theory of anhedonia in depression, and also emphasize the role of dopamine system abnormalities and altered brain structures or functional networks underpinning reward processing in the pathogenesis of anhedonia. Furthermore, to reinstate reward processing in depressed adults, various effective interventions for anhedonia have been developed, including direct psychosocial interventions, indirect working memory training, and real-time neurofeedback training with functional magnetic resonance imaging (fMRI). Future research needs to deeply investigate the role of stress and gene polymorphisms in the etiology and mechanism of anhedonia in depression. Besides, more attention should be paid to social anhedonia in depressed individuals. And we also emphasize the need to further promote translational studies on the clinical interventions of anhedonia.


World Health Organization. Depression. 2018. Available at: (accessed 2020).
Association, A. P. Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Arlington: American Psychiatric Association, 2000.
Hasler, G., Drevets, W. C., Manji, H. K., Charney, D. S. Discovering endophenotypes for major depression. Neuropsychopharmacology, 2004, 29(10): 1765–1781.
Bonanni, Gualtieri, Lester, Falcone, Nardella, Fiorillo, Pompili. Can anhedonia be considered a suicide risk factor? A review of the literature. Medicina, 2019, 55(8): 458.
Fawcett, J., Scheftner, W. A., Fogg, L., Clark, D. C., Young, M. A., Hedeker, D., Gibbons, R. D. Time-related predictors of suicide in major affective disorder. American Journal of Psychiatry, 1990, 147(9): 1189–1194.
Klonsky, E. D. What is emptiness? clarifying the 7th criterion for borderline personality disorder. Journal of Personality Disorders, 2008, 22(4): 418–426.
Morris, B. H., Bylsma, L. M., Rottenberg, J. Does emotion predict the course of major depressive disorder? A review of prospective studies. British Journal of Clinical Psychology, 2009, 48(3): 255–273.
Winer, E. S., Nadorff, M. R., Ellis, T. E., Allen, J. G., Herrera, S., Salem, T. Anhedonia predicts suicidal ideation in a large psychiatric inpatient sample. Psychiatry Research, 2014, 218(1–2): 124–128.
McMakin, D. L., Olino, T. M., Porta, G., Dietz, L. J., Emslie, G., Clarke, G., Wagner, K. D., Asarnow, J. R., Ryan, N. D., Birmaher, B. et al. Anhedonia predicts poorer recovery among youth with selective serotonin reuptake inhibitor treatment–resistant depression. Journal of the American Academy of Child & Adolescent Psychiatry, 2012, 51(4): 404–411.
Spijker, J., Bijl, R. V., de Graaf, R., Nolen, W. A. Determinants of poor 1-year outcome of DSM-III-R major depression in the general population: Results of the Netherlands Mental Health Survey and Incidence Study (NEMESIS). Acta Psychiatrica Scandinavica, 2001, 103(2): 122–130.
Uher, R., Perlis, R. H., Henigsberg, N., Zobel, A., Rietschel, M., Mors, O., Hauser, J., Dernovsek, M. Z., Souery, D., Bajs, M. et al. Depression symptom dimensions as predictors of antidepressant treatment outcome: Replicable evidence for interest-activity symptoms. Psychological Medicine, 2012, 42(5): 967–980.
Berridge, K. C., Robinson, T. E. Parsing reward. Trends in Neurosciences, 2003, 26(9): 507–513.
Chen, Y. M., Xu, J., Zhou, L., Zheng, Y. The time course of incentive processing in anticipatory and consummatory anhedonia. Journal of Affective Disorders, 2018, 238: 442–450.
Gard, D. E., Gard, M. G., Kring, A. M., John, O. P. Anticipatory and consummatory components of the experience of pleasure: A scale development study. Journal of Research in Personality, 2006, 40(6): 1086–1102.
Klein, D. Depression and anhedonia. In: Clark, D. C., Fawcett J. (eds.), Anhedonia and affect deficit states. New York: PMA Publishing, 1984: 1–14.
Treadway, M. T., Zald, D. H. Reconsidering anhedonia in depression: Lessons from translational neuroscience. Neuroscience & Biobehavioral Reviews, 2011, 35(3): 537–555.
Craske, M. G., Meuret, A. E., Ritz, T., Treanor, M., Dour, H. J. Treatment for anhedonia: A neuroscience driven approach. Depression and Anxiety, 2016, 33(10): 927–938.
Rømer Thomsen, K., Whybrow, P. C., Kringelbach, M. L. Reconceptualizing anhedonia: Novel perspectives on balancing the pleasure networks in the human brain. Frontiers in Behavioral Neuroscience, 2015, 9: 49.
Sanislow, C. A., Pine, D. S., Quinn, K. J., Kozak, M. J., Garvey, M. A., Heinssen, R. K., Wang, P. S. E., Cuthbert, B. N. Developing constructs for psychopathology research: Research domain criteria. Journal of Abnormal Psychology, 2010, 119(4): 631–639.
Gooding, D. C., Pflum, M. J. The Anticipatory and consummatory interpersonal pleasure scale (ACIPS). Madison: University of Wisconsin, 2011.
Gooding, D. C., Pflum, M. J. The assessment of interpersonal pleasure: Introduction of the Anticipatory and Consummatory Interpersonal Pleasure Scale (ACIPS) and preliminary findings. Psychiatry Research, 2014, 215(1): 237–243.
Knutson, B., Westdorp, A., Kaiser, E., Hommer, D. FMRI visualization of brain activity during a monetary incentive delay task. NeuroImage, 2000, 12(1): 20–27.
Smoski, M. J., Rittenberg, A., Dichter, G. S. Major depressive disorder is characterized by greater reward network activation to monetary than pleasant image rewards. Psychiatry Research, 2011, 194(3): 263–270.
Lutz, K., Widmer, M. What can the monetary incentive delay task tell us about the neural processing of reward and punishment? Neuroscience and Neuroeconomics, 2014: 33.
Forbes, E. E., Hariri, A. R., Martin, S. L., Silk, J. S., Moyles, D. L., Fisher, P. M., Brown, S. M., Ryan, N. D., Birmaher, B., Axelson, D. A. et al. Altered striatal activation predicting real-world positive affect in adolescent major depressive disorder. American Journal of Psychiatry, 2009, 166(1): 64–73.
Liu, W. H., Chan, R. C. K., Wang, L. Z., Huang, J., Cheung, E. F. C., Gong, Q. Y., Gollan, J. K. Deficits in sustaining reward responses in subsyndromal and syndromal major depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2011, 35(4): 1045–1052.
Sherdell, L., Waugh, C. E., Gotlib, I. H. Anticipatory pleasure predicts motivation for reward in major depression. Journal of Abnormal Psychology, 2012, 121(1): 51–60.
Xiong, Z., Zheng, S., Xie, W., Zhu, L., Meng, S., Wang, T. Correlation study of anhedonia and incentive motivation impairment in depression patients. Journal of Clinical Psychosomatic Disease, 2013, 19(6): 528–531.
Yang, X. H., Huang, J., Zhu, C. Y., Wang, Y. F., Cheung, E. F. C., Chan, R. C. K., Xie, G. R. Motivational deficits in effort-based decision making in individuals with subsyndromal depression, first-episode and remitted depression patients. Psychiatry Research, 2014, 220(3): 874–882.
McFarland, B. R., Klein, D. N. Emotional reactivity in depression: Diminished responsiveness to anticipated reward but not to anticipated punishment or to nonreward or avoidance. Depression and Anxiety, 2009, 26(2): 117–122.
Pizzagalli, D. A., Holmes, A. J., Dillon, D. G., Goetz, E. L., Birk, J. L., Bogdan, R., Dougherty, D. D., Iosifescu, D. V., Rauch, S. L., Fava, M. Reduced caudate and nucleus accumbens response to rewards in unmedicated individuals with major depressive disorder. American Journal of Psychiatry, 2009, 166(6): 702–710.
Knutson, B., Bhanji, J. P., Cooney, R. E., Atlas, L. Y., Gotlib, I. H. Neural responses to monetary incentives in major depression. Biological Psychiatry, 2008, 63(7): 686–692.
Ubl, B., Kuehner, C., Kirsch, P., Ruttorf, M., Diener, C., Flor, H. Altered neural reward and loss processing and prediction error signalling in depression. Social Cognitive and Affective Neuroscience, 2015, 10(8): 1102–1112.
Jarbo, K., Verstynen, T. D. Converging structural and functional connectivity of orbitofrontal, dorsolateral prefrontal, and posterior parietal cortex in the human striatum. Journal of Neuroscience, 2015, 35(9): 3865–3878.
Stoy, M., Schlagenhauf, F., Sterzer, P., Bermpohl, F., Hägele, C., Suchotzki, K., Schmack, K., Wrase, J., Ricken, R., Knutson, B., et al. Hyporeactivity of ventral striatum towards incentive stimuli in unmedicated depressed patients normalizes after treatment with escitalopram. Journal of Psychopharmacology, 2012, 26(5): 677–688.
Smoski, M. J., Felder, J., Bizzell, J., Green, S. R., Ernst, M., Lynch, T. R., Dichter, G. S. fMRI of alterations in reward selection, anticipation, and feedback in major depressive disorder. Journal of Affective Disorders, 2009, 118(1–3): 69–78.
Gorka, S. M., Huggins, A. A., Fitzgerald, D. A., Nelson, B. D., Phan, K. L., Shankman, S. A. Neural response to reward anticipation in those with depression with and without panic disorder. Journal of Affective Disorders, 2014, 164: 50–56.
Zhang, W. N., Chang, S. H., Guo, L. Y., Zhang, K. L., Wang, J. The neural correlates of reward-related processing in major depressive disorder: A meta-analysis of functional magnetic resonance imaging studies. Journal of Affective Disorders, 2013, 151(2): 531–539.
Pizzagalli, D. A. Depression, stress, and anhedonia: Toward a synthesis and integrated model. Annual Review of Clinical Psychology, 2014, 10(1): 393–423.
Balleine, B. W., Delgado, M. R., Hikosaka, O. The role of the dorsal striatum in reward and decision-making. Journal of Neuroscience, 2007, 27(31): 8161–8165.
Haber, S. N., Knutson, B. The reward circuit: Linking primate anatomy and human imaging. Neuropsychopharmacology, 2010, 35(1): 4–26.
Wallis, J. D., Kennerley, S. W. Heterogeneous reward signals in prefrontal cortex. Current Opinion in Neurobiology, 2010, 20(2): 191–198.
Zhang, B., Lin, P., Shi, H. Q., Öngür, D., Auerbach, R. P., Wang, X. S., Yao, S. Q., Wang, X. Mapping anhedonia-specific dysfunction in a transdiagnostic approach: An ALE meta-analysis. Brain Imaging and Behavior, 2016, 10(3): 920–939.
Hallford, D. J., Barry, T. J., Austin, D. W., Raes, F., Takano, K., Klein, B. Impairments in episodic future thinking for positive events and anticipatory pleasure in major depression. Journal of Affective Disorders, 2020, 260: 536–543.
Franken, I. H. A., Rassin, E., Muris, P. The assessment of anhedonia in clinical and non-clinical populations: Further validation of the Snaith–Hamilton Pleasure Scale (SHAPS). Journal of Affective Disorders, 2007, 99(1–3): 83–89.
Snaith, R. P., Hamilton, M., Morley, S., Humayan, A., Hargreaves, D., Trigwell, P. A scale for the assessment of hedonic tone the snaith–Hamilton pleasure scale. British Journal of Psychiatry, 1995, 167(1): 99–103.
Martinotti, G., Sepede, G., Gambi, F., di Iorio, G., de Berardis, D., di Nicola, M., Onofrj, M., Janiri, L., di Giannantonio, M. Agomelatine versus venlafaxine XR in the treatment of anhedonia in major depressive disorder. Journal of Clinical Psychopharmacology, 2012, 32(4): 487–491.
Fawcett, J., Clark, D. C., Scheftner, W. A., Gibbons, R. D. Assessing anhedonia in psychiatric patients: The Pleasure Scale. Archives of General Psychiatry, 1983, 40(1), 79–84.
Leventhal, A. M., Chasson, G. S., Tapia, E., Miller, E. K., Pettit, J. W. Measuring hedonic capacity in depression: A psychometric analysis of three anhedonia scales. Journal of Clinical Psychology, 2006, 62(12): 1545–1558.
Chapman, L. J., Chapman, J. P., Raulin, M. L. Scales for physical and social anhedonia. Journal of Abnormal Psychology, 1976, 85(4): 374–382.
Rizvi, S. J., Quilty, L. C., Sproule, B. A., Cyriac, A., Michael Bagby, R., Kennedy, S. H. Development and validation of the Dimensional Anhedonia Rating Scale (DARS) in a community sample and individuals with major depression. Psychiatry Research, 2015, 229(1–2): 109–119.
Forbes, E. E., Brown, S. M., Kimak, M., Ferrell, R. E., Manuck, S. B., Hariri, A. R. Genetic variation in components of dopamine neurotransmission impacts ventral striatal reactivity associated with impulsivity. Molecular Psychiatry, 2009, 14(1): 60–70.
Rottenberg, J., Kasch, K. L., Gross, J. J., Gotlib, I. H. Sadness and amusement reactivity differentially predict concurrent and prospective functioning in major depressive disorder. Emotion (Washington, D.C.), 2002, 2(2): 135–146.
Stuhrmann, A., Dohm, K., Kugel, H., Zwanzger, P., Redlich, R., Grotegerd, D., Rauch, A., Arolt, V., Heindel, W., Suslow, T., et al. Mood-congruent amygdala responses to subliminally presented facial expressions in major depression: Associations with anhedonia. Journal of Psychiatry & Neuroscience, 2013, 38(4): 249–258.
Dichter, G. S., Smoski, M. J., Kampov-Polevoy, A. B., Gallop, R., Garbutt, J. C. Unipolar depression does not moderate responses to the Sweet Taste Test. Depression and Anxiety, 2010, 27(9): 859–863.
McCabe, C., Cowen, P. J., Harmer, C. J. Neural representation of reward in recovered depressed patients. Psychopharmacology, 2009, 205(4): 667–677.
Duffy, V. B., Bartoshuk, L. M. Food acceptance and genetic variation in taste. Journal of the American Dietetic Association, 2000, 100(6): 647–655.
Berenbaum, H., Oltmanns, T. F. Emotional experience and expression in schizophrenia and depression. Journal of Abnormal Psychology, 1992, 101(1): 37–44.
Kaviani, H., Gray, J. A., Checkley, S. A., Raven, P. W., Wilson, G. D., Kumari, V. Affective modulation of the startle response in depression: Influence of the severity of depression, anhedonia, and anxiety. Journal of Affective Disorders, 2004, 83(1): 21–31.
Sloan, D. M., Strauss, M. E., Wisner, K. L. Diminished response to pleasant stimuli by depressed women. Journal of Abnormal Psychology, 2001, 110(3): 488–493.
Berlin, I., Givry-Steiner, L., Lecrubier, Y., Puech, A. J. Measures of anhedonia and hedonic responses to sucrose in depressive and schizophrenic patients in comparison with healthy subjects. European Psychiatry, 1998, 13(6): 303–309.
Dichter, G. S., Tomarken, A. J., Shelton, R. C., Sutton, S. K. Early- and late-onset startle modulation in unipolar depression. Psychophysiology, 2004, 41(3): 433–440.
Tsai, J. L., Pole, N., Levenson, R. W., Muñoz, R. F. The effects of depression on the emotional responses of Spanish-speaking Latinas. Cultural Diversity and Ethnic Minority Psychology, 2003, 9(1): 49–63.
Forbes, E. E., Miller, A., Cohn, J. F., Fox, N. A., Kovacs, M. Affect-modulated startle in adults with childhood-onset depression: Relations to bipolar course and number of lifetime depressive episodes. Psychiatry Research, 2005, 134(1): 11–25.
Epstein, J., Pan, H., Kocsis, J. H., Yang, Y. H., Butler, T., Chusid, J., Hochberg, H., Murrough, J., Strohmayer, E., Stern, E., et al. Lack of ventral striatal response to positive stimuli in depressed versus normal subjects. American Journal of Psychiatry, 2006, 163(10): 1784–1790.
Fu, C. H. Y., Williams, S. C. R., Brammer, M. J., Suckling, J., Kim, J., Cleare, A. J., Walsh, N. D., Mitterschiffthaler, M. T., Andrew, C. M., Pich, E. M. et al. Neural responses to happy facial expressions in major depression following antidepressant treatment. American Journal of Psychiatry, 2007, 164(4): 599–607.
Surguladze, S., Brammer, M. J., Keedwell, P., Giampietro, V., Young, A. W., Travis, M. J., Williams, S. C. R., Phillips, M. L. A differential pattern of neural response toward sad versus happy facial expressions in major depressive disorder. Biological Psychiatry, 2005, 57(3): 201–209.
Canli, T., Sivers, H., Thomason, M. E., Whitfield-Gabrieli, S., Gabrieli, J. D. E., Gotlib, I. H. Brain activation to emotional words in depressed vs healthy subjects. Neuroreport, 2004, 15(17): 2585–2588.
Gotlib, I. H., Sivers, H., Gabrieli, J. D. E., Whitfield-Gabrieli, S., Goldin, P., Minor, K. L., Canli, T. Subgenual anterior cingulate activation to valenced emotional stimuli in major depression. Neuroreport, 2005, 16(16): 1731–1734.
Keedwell, P. A., Andrew, C., Williams, S. C. R., Brammer, M. J., Phillips, M. L. A double dissociation of ventromedial prefrontal cortical responses to sad and happy stimuli in depressed and healthy individuals. Biological Psychiatry, 2005, 58(6): 495–503.
Yuan, J. W., Kring, A. M. Dysphoria and the prediction and experience of emotion. Cognition and Emotion, 2009, 23(6): 1221–1232.
Pizzagalli, D. A., Jahn, A. L., O'Shea, J. P. Toward an objective characterization of an anhedonic phenotype: A signal-detection approach. Biological Psychiatry, 2005, 57(4): 319–327.
Kumar, P., Waiter, G., Ahearn, T., Milders, M., Reid, I., Steele, J. D. Abnormal temporal difference reward-learning signals in major depression. Brain, 2008, 131(8): 2084–2093.
Gradin, V. B., Kumar, P., Waiter, G., Ahearn, T., Stickle, C., Milders, M., Reid, I., Hall, J., Steele, J. D. Expected value and prediction error abnormalities in depression and schizophrenia. Brain, 2011, 134(6): 1751–1764.
Dombrovski, A. Y., Clark, L., Siegle, G. J., Butters, M. A., Ichikawa, N., Sahakian, B. J., Szanto, K. Reward/punishment reversal learning in older suicide attempters. American Journal of Psychiatry, 2010, 167(6): 699–707.
Pizzagalli, D. A., Iosifescu, D., Hallett, L. A., Ratner, K. G., Fava, M. Reduced hedonic capacity in major depressive disorder: Evidence from a probabilistic reward task. Journal of Psychiatric Research, 2008, 43(1): 76–87.
Chen, C., Takahashi, T., Nakagawa, S., Inoue, T., Kusumi, I. Reinforcement learning in depression: A review of computational research. Neuroscience & Biobehavioral Reviews, 2015, 55: 247–267.
Vrieze, E., Pizzagalli, D. A., Demyttenaere, K., Hompes, T., Sienaert, P., de Boer, P., Schmidt, M., Claes, S. Reduced reward learning predicts outcome in major depressive disorder. Biological Psychiatry, 2013, 73(7): 639–645.
Pechtel, P., Dutra, S. J., Goetz, E. L., Pizzagalli, D. A. Blunted reward responsiveness in remitted depression. Journal of Psychiatric Research, 2013, 47(12): 1864–1869.
Cooper, J. A., Gorlick, M. A., Denny, T., Worthy, D. A., Beevers, C. G., Maddox, W. T. Training attention improves decision making in individuals with elevated self-reported depressive symptoms. Cognitive, Affective, & Behavioral Neuroscience, 2014, 14(2): 729–741.
Chase, H. W., Frank, M. J., Michael, A., Bullmore, E. T., Sahakian, B. J., Robbins, T. W. Approach and avoidance learning in patients with major depression and healthy controls: Relation to anhedonia. Psychological Medicine, 2010, 40(3): 433–440.
Dombrovski, A. Y., Szanto, K., Clark, L., Reynolds, C. F., Siegle, G. J. Reward signals, attempted suicide, and impulsivity in late-life depression. JAMA Psychiatry, 2013, 70(10): 1.
Glimcher, P. W. Understanding dopamine and reinforcement learning: The dopamine reward prediction error hypothesis. PNAS, 2011, 108(Supplement_3): 15647–15654.
Niv, Y. Reinforcement learning in the brain. Journal of Mathematical Psychology, 2009, 53(3): 139–154.
Schultz, W. Dopamine signals for reward value and risk: Basic and recent data. Behavioral and Brain Functions, 2010, 6(1): 1–9.
Geugies, H., Mocking, R. J. T., Figueroa, C. A., Groot, P. F. C., Marsman, J. B. C., Servaas, M. N., Steele, J. D., Schene, A. H., Ruhé, H. G. Impaired reward-related learning signals in remitted unmedicated patients with recurrent depression. Brain, 2019, 142(8): 2510–2522.
Rothkirch, M., Tonn, J., Köhler, S., Sterzer, P. Neural mechanisms of reinforcement learning in unmedicated patients with major depressive disorder. Brain, 2017, 140(4): 1147–1157.
Treadway, M. T., Buckholtz, J. W., Schwartzman, A. N., Lambert, W. E., Zald, D. H. Worth the ‘EEfRT’? the effort expenditure for rewards task as an objective measure of motivation and anhedonia. PLoS One, 2009, 4(8): e6598.
Treadway, M. T., Bossaller, N. A., Shelton, R. C., Zald, D. H. Effort-based decision-making in major depressive disorder: A translational model of motivational anhedonia. Journal of Abnormal Psychology, 2012, 121(3): 553–558.
Cléry-Melin, M. L., Schmidt, L., Lafargue, G., Baup, N., Fossati, P., Pessiglione, M. Why don't You try harder? an investigation of effort production in major depression. PLoS One, 2011, 6(8): e23178.
Brinkmann, K., Franzen, J. Not everyone's heart contracts to reward: Insensitivity to varying levels of reward in dysphoria. Biological Psychology, 2013, 94(2): 263–271.
Brinkmann, K., Schüpbach, L., Joye, I. A., Gendolla, G. H. E. Anhedonia and effort mobilization in dysphoria: Reduced cardiovascular response to reward and punishment. International Journal of Psychophysiology, 2009, 74(3): 250–258.
Brinkmann, K., Franzen, J. Blunted cardiovascular reactivity during social reward anticipation in subclinical depression. International Journal of Psychophysiology, 2017, 119: 119–126.
Brinkmann, K., Franzen, J., Rossier, C., Gendolla, G. H. E. I don’t care about others’ approval: Dysphoric individuals show reduced effort mobilization for obtaining a social reward. Motivation and Emotion, 2014, 38(6): 790–801.
Ingram, R. E., Luxton, D. D. Vulnerability-stress models. In: Hankin, B. L., Abela, J. R. (eds.) Development of Psychopathology: A Vulnerability-Stress Perspective. Los Angeles: SAGE Publications, Inc., 2005: 32–46.
Loas, G. Vulnerability to depression: A model centered on anhedonia. Journal of Affective Disorders, 1996, 41(1): 39–53.
Dreher, J. C., Kohn, P., Kolachana, B., Weinberger, D. R., Berman, K. F. Variation in dopamine genes influences responsivity of the human reward system. PNAS, 2009, 106(2): 617–622.
Yacubian, J., Sommer, T., Schroeder, K., Glascher, J., Kalisch, R., Leuenberger, B., Braus, D. F., Buchel, C. Gene gene interaction associated with neural reward sensitivity. PNAS, 2007, 104(19): 8125–8130.
Boecker-Schlier, R., Holz, N. E., Buchmann, A. F., Blomeyer, D., Plichta, M. M., Jennen-Steinmetz, C., Wolf, I., Baumeister, S., Treutlein, J., Rietschel, M. et al. Interaction between COMT Val(158)Met polymorphism and childhood adversity affects reward processing in adulthood. NeuroImage, 2016, 132: 556–570.
Dan, F. T., Hajcak, G. Genetic variation in dopamine moderates neural response during reward anticipation and delivery: Evidence from event-related potentials. Psychophysiology, 2012, 49(5): 617–626.
Aarts, E., Roelofs, A., Franke, B., Rijpkema, M., Fernandez, G., Helmich, R. C., Cools, R. Striatal dopamine mediates the interface between motivational and cognitive control in humans: Evidence from genetic imaging. Neuropsychopharmacology, 2010, 35(9): 1943–1951.
Wittmann, B. C., Tan, G. C., Lisman, J. E., Dolan, R. J., Düzel, E. Reprint of: DAT genotype modulates striatal processing and long-term memory for items associated with reward and punishment. Neuropsychologia, 2013, 51(12): 2469–2477.
Jia, T. Y., Macare, C., Desrivières, S., Gonzalez, D. A., Tao, C. Y., Ji, X. X., Ruggeri, B., Nees, F., Banaschewski, T., Barker, G. J. et al. Neural basis of reward anticipation and its genetic determinants. PNAS, 2016, 113(14): 3879–3884.
Cohen, M. X., Young, J., Baek, J. M., Kessler, C., Ranganath, C. Individual differences in extraversion and dopamine genetics predict neural reward responses. Brain Research. Cognitive Brain Research, 2005, 25(3): 851–861.
Dillon, D. G., Bogdan, R., Fagerness, J., Holmes, A. J., Perlis, R. H., Pizzagalli, D. A. Variation in TREK1 gene linked to depression-resistant phenotype is associated with potentiated neural responses to rewards in humans. Human Brain Mapping, 2009, 31(2): 210–221.
Lancaster, T. M., Ihssen, N., Brindley, L. M., Linden, D. J. Further support for association between GWAS variant for positive emotion and reward systems. Translational Psychiatry, 2017, 7(1): e1018.
Corral-Frías, N. S., Pizzagalli, D. A., Carré, J. M., Michalski, L. J., Nikolova, Y. S., Perlis, R. H., Fagerness, J., Lee, M. R., Conley, E. D., Lancaster, T. M. et al. COMT Val(158) Met genotype is associated with reward learning: A replication study and meta-analysis. Genes, Brain, and Behavior, 2016, 15(5): 503–513.
Lancaster, T. M., Heerey, E. A., Mantripragada, K., Linden, D. E. J. Replication study implicates COMT val158met polymorphism as a modulator of probabilistic reward learning. Genes, Brain, and Behavior, 2015, 14(6): 486–492.
Lancaster, T. M., Linden, D. E., Heerey, E. A. COMT val158met predicts reward responsiveness in humans. Genes, Brain, and Behavior, 2012, 11(8): 986–992.
Nikolova, Y., Bogdan, R., Pizzagalli, D. A. Perception of a naturalistic stressor interacts with 5-HTTLPR/rs25531 genotype and gender to impact reward responsiveness. Neuropsychobiology, 2012, 65(1): 45–54.
Bogdan, R., Santesso, D. L., Fagerness, J., Perlis, R. H., Pizzagalli, D. A. Corticotropin-releasing hormone receptor type 1 (CRHR1) genetic variation and stress interact to influence reward learning. The Journal of Neuroscience, 2011, 31(37): 13246–13254.
Nikolova, Y. S., Ferrell, R. E., Manuck, S. B., Hariri, A. R. Multilocus genetic profile for dopamine signaling predicts ventral striatum reactivity. Neuropsychopharmacology, 2011, 36(9): 1940–1947.
Stice, E., Yokum, S., Burger, K., Epstein, L., Smolen, A. Multilocus genetic composite reflecting dopamine signaling capacity predicts reward circuitry responsivity. Journal of Neuroscience, 2012, 32(29): 10093–10100.
Bogdan, R., Nikolova, Y. S., Pizzagalli, D. A. Neurogenetics of depression: A focus on reward processing and stress sensitivity. Neurobiology of Disease, 2013, 52: 12–23.
Beck, A. T. Cognitive therapy and the emotional disorders. Oxford: International Universities Press, 1976.
Ellis, A. J., Beevers, C. G., Wells, T. T. Attention allocation and incidental recognition of emotional information in dysphoria. Cognitive Therapy and Research, 2011, 35(5): 425–433.
Mogg, K., Bradley, B. P. Attentional bias in generalized anxiety disorder versus depressive disorder. Cognitive Therapy and Research, 2005, 29(1): 29–45.
Brailean, A. M., Koster, E. H. W., Hoorelbeke, K., de Raedt, R. Attentional modulation by reward and punishment cues in relation to depressive symptoms. Journal of Behavior Therapy and Experimental Psychiatry, 2014, 45(3): 351–359.
Salem, T., Winer, E. S., Nadorff, M. R. Combined behavioural markers of cognitive biases are associated with anhedonia. Cognition and Emotion, 2018, 32(2): 422–430.
Stanton, C. H., Holmes, A. J., Chang, S. W. C., Joormann, J. From stress to anhedonia: Molecular processes through functional circuits. Trends in Neurosciences, 2019, 42(1): 23–42.
Bekris, S., Antoniou, K., Daskas, S., Papadopoulou-Daifoti, Z. Behavioural and neurochemical effects induced by chronic mild stress applied to two different rat strains. Behavioural Brain Research, 2005, 161(1): 45–59.
Rüedi-Bettschen, D., Pedersen, E. M., Feldon, J., Pryce, C. R. Early deprivation under specific conditions leads to reduced interest in reward in adulthood in Wistar rats. Behavioural Brain Research, 2005, 156(2): 297–310.
Mintz, M., Rüedi-Bettschen, D., Feldon, J., Pryce, C. R. Early social and physical deprivation leads to reduced social motivation in adulthood in Wistar rats. Behavioural Brain Research, 2005, 156(2): 311–320.
Al'Absi, M., Nakajima, M., Hooker, S., Wittmers, L., Cragin, T. Exposure to acute stress is associated with attenuated sweet taste. Psychophysiology, 2012, 49(1): 96–103.
Berenbaum, H., Connelly, J. The effect of stress on hedonic capacity. Journal of Abnormal Psychology, 1993, 102(3): 474–481.
Bogdan, R., Pizzagalli, D. A. Acute stress reduces reward responsiveness: Implications for depression. Biological Psychiatry, 2006, 60(10): 1147–1154.
Berridge, K. C. The debate over dopamine's role in reward: The case for incentive salience. Psychopharmacology, 2007, 191(3): 391–431.
Schultz, W. Predictive reward signal of dopamine neurons. Journal of Neurophysiology, 1998, 80(1): 1–27.
Björklund, A., Dunnett, S. B. Dopamine neuron systems in the brain: An update. Trends in Neurosciences, 2007, 30(5): 194–202.
Mitani, H., Shirayama, Y., Yamada, T., Kawahara, R. Plasma levels of homovanillic acid, 5-hydroxyindoleacetic acid and cortisol, and serotonin turnover in depressed patients. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2006, 30(3): 531–534.
Mitani, H., Shirayama, Y., Yamada, T., Kawahara, R. Plasma levels of homovanillic acid, 5-hydroxyindoleacetic acid and cortisol, and serotonin turnover in depressed patients. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2006, 30(3): 531–534.
Holmes, E. A., Mathews, A., Dalgleish, T., MacKintosh, B. Positive interpretation training: Effects of mental imagery versus verbal training on positive mood. Behavior Therapy, 2006, 37(3): 237–247.
Holmes, E. A., Lang, T. J., Shah, D. M. Developing interpretation bias modification as a “cognitive vaccine” for depressed mood: Imagining positive events makes You feel better than thinking about them verbally. Journal of Abnormal Psychology, 2009, 118(1): 76–88.
Murphy, S. E., O’Donoghue, M. C., Blackwell, S. E., Nobre, A. C., Browning, M., Holmes, E. A. Increased rostral anterior cingulate activity following positive mental imagery training in healthy older adults. Social Cognitive and Affective Neuroscience, 2017, 12(12): 1950–1958.
Torkan, H., Blackwell, S. E., Holmes, E. A., Kalantari, M., Neshat-Doost, H. T., Maroufi, M., Talebi, H. Positive imagery cognitive bias modification in treatment-seeking patients with major depression in Iran: A pilot study. Cognitive Therapy and Research, 2014, 38(2): 132–145.
Williams, A. D., O’Moore, K., Blackwell, S. E., Smith, J., Holmes, E. A., Andrews, G. Positive imagery cognitive bias modification (CBM) and Internet-based cognitive behavioral therapy (iCBT): A randomized controlled trial. Journal of Affective Disorders, 2015, 178: 131–141.
Holmes, E. A., Mathews, A., MacKintosh, B., Dalgleish, T. The causal effect of mental imagery on emotion assessed using picture-word cues. Emotion (Washington, D.C.), 2008, 8(3): 395–409
Pictet, A., Coughtrey, A. E., Mathews, A., Holmes, E. A. Fishing for happiness: The effects of generating positive imagery on mood and behaviour. Behaviour Research and Therapy, 2011, 49(12): 885–891.
Blackwell, S. E., Holmes, E. A. Modifying interpretation and imagination in clinical depression: A single case series using cognitive bias modification. Applied Cognitive Psychology, 2010, 24(3): 338–350.
Lang, T. J., Blackwell, S. E., Harmer, C. J., Davison, P., Holmes, E. A. Cognitive bias modification using mental imagery for depression: Developing a novel computerized intervention to change negative thinking styles. European Journal of Personality, 2012, 26(2): 145–157.
Blackwell, S. E., Browning, M., Mathews, A., Pictet, A., Welch, J., Davies, J., Watson, P., Geddes, J. R., Holmes, E. A. Positive imagery-based cognitive bias modification as a web-based treatment tool for depressed adults: A randomized controlled trial. Clinical Psychological Science, 2015, 3(1): 91–111.
Renner, F., Ji, J. L., Pictet, A., Holmes, E. A., Blackwell, S. E. Effects of engaging in repeated mental imagery of future positive events on behavioural activation in individuals with major depressive disorder. Cognitive Therapy and Research, 2017, 41(3): 369–380.
McMakin, D. L., Siegle, G. J., Shirk, S. R. Positive affect stimulation and sustainment (PASS) module for depressed mood: A preliminary investigation of treatment-related effects. Cognitive Therapy and Research, 2011, 35(3): 217–226.
Taylor, C. T., Lyubomirsky, S., Stein, M. B. Upregulating the positive affect system in anxiety and depression: Outcomes of a positive activity intervention. Depression and Anxiety, 2017, 34(3): 267–280.
Christopher deCharms, R. Applications of real-time fMRI. Nature Reviews Neuroscience, 2008, 9(9): 720–729.
Drevets, W. C., Price, J. L., Furey, M. L. Brain structural and functional abnormalities in mood disorders: Implications for neurocircuitry models of depression. Brain Structure and Function, 2008, 213(1–2): 93–118.
Sergerie, K., Chochol, C., Armony, J. L. The role of the amygdala in emotional processing: A quantitative meta-analysis of functional neuroimaging studies. Neuroscience & Biobehavioral Reviews, 2008, 32(4): 811–830.
Young, K. D., Siegle, G. J., Bodurka, J., Drevets, W. C. Amygdala activity during autobiographical memory recall in depressed and vulnerable individuals: Association with symptom severity and autobiographical overgenerality. American Journal of Psychiatry, 2016, 173(1): 78–89.
Young, K. D., Siegle, G. J., Zotev, V., Phillips, R., Misaki, M., Yuan, H., Drevets, W. C., Bodurka, J. Randomized clinical trial of real-time fMRI amygdala neurofeedback for major depressive disorder: Effects on symptoms and autobiographical memory recall. American Journal of Psychiatry, 2017, 174(8): 748–755.
Young, K. D., Zotev, V., Phillips, R., Misaki, M., Yuan, H., Drevets, W. C., Bodurka, J. Real-time FMRI neurofeedback training of amygdala activity in patients with major depressive disorder. PLoS One, 2014, 9(2): e88785.
Zhang, Y. J., Wang, H. Y., Yan, C., Wang, L. L., Cheung, E. F. C., Chan, R. C. K. Working memory training can improve anhedonia in college students with subsyndromal depressive symptoms. PsyCh Journal, 2019, 8(4): 401–410.
Jaeggi, S. M., Buschkuehl, M., Jonides, J., Perrig, W. J. Improving fluid intelligence with training on working memory. PNAS, 2008, 105(19): 6829–6833.
Dunn, B. D. Helping depressed clients reconnect to positive emotion experience: Current insights and future directions. Clinical Psychology & Psychotherapy, 2012, 19(4): 326–340.
Shankman, S. A., Katz, A. C., DeLizza, A. A., Sarapas, C., Gorka, S. M., Campbell, M. L. The different facets of anhedonia and their associations with different psychopathologies. In: Ritsner, M., (ed.) Anhedonia: A Comprehensive Handbook Volume I, Dordrecht: Springer, 2014: 3–22.
Kupferberg, A., Bicks, L., Hasler, G. Social functioning in major depressive disorder. Neuroscience & Biobehavioral Reviews, 2016, 69: 313–332.
He, Z., Zhang, D. Social feedback deficits in individuals with depression: The state of art and unsolved problems. Journal of Psychological Science, 2018, 41(1): 237–243. (in Chinese)
Stress and Brain
Pages 11-32
Cite this article:
Mao J, Yuan J. Anhedonia and its intervention in depressive adults: New developments based on Research Domain Criteria (RDoC) in mental illnesses. Stress and Brain, 2021, 1(1): 11-32.








Received: 29 February 2020
Revised: 30 May 2020
Accepted: 22 July 2020
Published: 23 December 2020
© The Author(s) 2020

Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( which permits non-commercial use, reproduction and distribution of the work without further permission.