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Shared and distinct reward neural mechanisms among patients with schizophrenia, major depressive disorder, and bipolar disorder: an effort-based functional imaging study

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Abstract

Unwillingness to exert effort for rewards has been found in patients with schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BD), but the underlying shared and distinct reward neural mechanisms remain unclear. This study aimed to compare the neural correlates of such impairments across different diagnoses. The neural responses in an effort-expenditure for reward task (EEfRT) were assessed in 20 SCZ patients, 23 MDD patients, 17 BD patients, and 30 healthy controls (HC). The results found shared activation in the cingulate gyrus, the medial frontal gyrus, and the middle frontal gyrus during the EEfRT administration. Compared to HC, SCZ patients exhibited stronger variations of functional connectivity between the right caudate and the left amygdala, the left hippocampus and the left putamen, with increase in reward magnitude. In MDD patients, an enhanced activation compared to HC in the right superior temporal gyrus was found with the increase of reward magnitude. The variations of functional connectivity between the caudate and the right cingulate gyrus, the left postcentral gyrus and the left inferior parietal lobule with increase in reward magnitude were weaker than that found in HC. In BD patients, the degree of activation in the left precuneus was increased, but that in the left dorsolateral prefrontal cortex was decreased with increase in reward probability compared to HC. These findings demonstrate both shared and distinct reward neural mechanisms associated with EEfRT in patients with SCZ, MDD, and BD, implicating potential intervention targets to alleviate amotivation in these clinical disorders.

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Original data of this study are available on request.

References

  1. Alloy LB, Abramson LY, Walshaw PD, Cogswell A, Grandin LD, Hughes ME, Iacoviello BM, Whitehouse WG, Urosevic S, Nusslock R, Hogan ME (2008) Behavioral approach system and behavioral inhibition system sensitivities and bipolar spectrum disorders: prospective prediction of bipolar mood episodes. Bipolar Disord 10:310–322

    Article  PubMed  Google Scholar 

  2. Alloy LB, Bender RE, Whitehouse WG, Wagner CA, Liu RT, Grant DA, Jager-Hyman S, Molz A, Choi JY, Harmon-Jones E, Abramson LY (2012) High behavioral approach system (BAS) sensitivity, reward responsiveness, and goal-striving predict first onset of bipolar spectrum disorders: a prospective behavioral high-risk design. J Abnorm Psychol 121:339–351

    Article  PubMed  Google Scholar 

  3. Alloy LB, Olino T, Freed RD, Nusslock R (2016) Role of reward sensitivity and processing in major depressive and bipolar spectrum disorders. Behav Ther 47:600–621

    Article  PubMed  PubMed Central  Google Scholar 

  4. Annett M (1970) Classification of hand preference by association analysis. Br J Psychol 61(3):303–321

    Article  CAS  PubMed  Google Scholar 

  5. Arulpragasam AR, Cooper JA, Nuutinen MR, Treadway MT (2018) Corticoinsular circuits encode subjective value expectation and violation for effortful goal-directed behavior. Proc Natl Acad Sci U S A 115:E5233–E5242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Barch DM, Treadway MT, Schoen N (2014) Effort, anhedonia, and function in schizophrenia: reduced effort allocation predicts amotivation and functional impairment. J Abnorm Psychol 123:387–397

    Article  PubMed  PubMed Central  Google Scholar 

  7. Barkus E, Badcock JC (2019) A transdiagnostic perspective on social anhedonia. Front Psych 10:1–15

    Google Scholar 

  8. Bermpohl F, Dalanay U, Kahnt T, Sajonz B, Heimann H, Ricken R, Stoy M, Hã¤GeleSchlagenhaufAdli CFM (2010) A preliminary study of increased amygdala activation to positive affective stimuli in mania. Bipolar Disord 11:70–75

    Article  Google Scholar 

  9. Bernacer J, Martinez-Valbuena I, Martinez M, Pujol N, Luis E, Ramirez-Castillo D, Pastor MA (2018) Neural correlates of effort-based behavioral inconsistency. Cortex J Devoted Study Nerv Syst Behav 113:96–110

    Article  Google Scholar 

  10. Berridge KC, Kringelbach ML (2015) Pleasure systems in the brain. Neuron 86:646–664

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Brett M, Anton JL, Valabregue R, Poline JB (2002) Region of interest analysis using an spm toolbox. In: 8th international conference on functional mapping of the human brain, vol 16. No 2, p 497

  12. Burke CJ, Brunger C, Kahnt T, Park SQ, Tobler PN (2013) Neural integration of risk and effort costs by the frontal pole: only upon request. J Neurosci 33:1706–1713

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Chan RCK, Wang Y, Yan C, Zhao Q, McGrath J, Hsi X, Stone WS (2012) A study of trait anhedonia in non-clinical Chinese samples: evidence from the chapman scales for physical and social anhedonia. PLoS ONE 7:1–7

    Google Scholar 

  14. Chapman LJ, Chapman JP, Raulin ML (1976) Scales for physical and social anhedonia. J Abnorm Psychol 85:374

    Article  CAS  PubMed  Google Scholar 

  15. Chase HW, Nusslock R, Almeida JR, Forbes EE, LaBarbara EJ, Phillips ML (2013) Dissociable patterns of abnormal frontal cortical activation during anticipation of an uncertain reward or loss in bipolar versus major depression. Bipolar Disord 15:839–854

    Article  PubMed  PubMed Central  Google Scholar 

  16. Der-Avakian A, Markou A (2012) The neurobiology of anhedonia and other reward-related deficits. Trends Neurosci 35:68–77

    Article  CAS  PubMed  Google Scholar 

  17. Dragovic M, Hammond G (2005) Handedness in schizophrenia: a quantitative review of evidence. Acta Psychiatr Scand 111:410–419

    Article  CAS  PubMed  Google Scholar 

  18. Dunlop K, Rizvi SJ, Kennedy SH, Hassel S, Strother SC, Harris JK, Zamyadi M, Arnott SR, Davis AD, Mansouri F, Schulze L, Ceniti AK, Lam RW, Milev R, Rotzinger S, Foster JA, Frey BN, Parikh SV, Soares CN, Uher R, Turecki G, MacQueen GM, Downar J (2020) Clinical, behavioral, and neural measures of reward processing correlate with escitalopram response in depression: a Canadian biomarker integration network in depression (CAN-BIND-1) report. Neuropsychopharmacology. https://doi.org/10.1038/s41386-020-0688-x

    Article  PubMed  PubMed Central  Google Scholar 

  19. Eckblad M, Chapman LJ, Chapman JP, Mishlove M (1982) The revised social anhedonia scale. Unpublished test

  20. Fervaha G, Graff-Guerrero A, Zakzanis KK, Foussias G, Agid O, Remington G (2013) Incentive motivation deficits in schizophrenia reflect effort computation impairments during cost-benefit decision-making. J Psychiatr Res 47:1590–1596

    Article  PubMed  Google Scholar 

  21. Friston KJ, Buechel C, Fink GR, Morris J, Rolls E, Dolan RJ (1997) Psychophysiological and modulatory interactions in neuroimaging. Neuroimage 6:218–229

    Article  CAS  PubMed  Google Scholar 

  22. Friston KJ, Williams S, Howard R, Frackowiak RSJ, Turner R (1996) Movement-related effects in fmri time-series. Magn Reson Med 35:346–355

    Article  CAS  PubMed  Google Scholar 

  23. Fusar-Poli P, Meyer-Lindenberg A (2013) Striatal presynaptic dopamine in schizophrenia, part II: meta-analysis of F-18/C-11 -DOPA PET studies. Schizophr Bull 39:33–42

    Article  PubMed  Google Scholar 

  24. Gold JM, Strauss GP, Waltz JA, Robinson BM, Brown JK, Frank MJ (2013) Negative symptoms of schizophrenia are associated with abnormal effort-cost computations. Biol Psychiatry 74:130–136

    Article  PubMed  PubMed Central  Google Scholar 

  25. Gong Y (1992) Wechsler adult intelligence scale-revised in china version. Hunan Medical College, Changsha, Hunan/China

    Google Scholar 

  26. Hartmann MN, Hager OM, Reimann AV, Chumbley JR, Kirschner M, Seifritz E, Tobler P, Kaiser S (2014) Apathy but not diminished expression in schizophrenia is associated with discounting of monetary rewards by physical effort. Schizophr Bull 2:1–10

    Google Scholar 

  27. Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Hirschfeld RM, Williams JB, Spitzer RL, Calabrese JR, Flynn L, Keck PE Jr, Lewis L, McElroy SL, Post RM, Rapport DJ (2000) Development and validation of a screening instrument for bipolar spectrum disorder: the mood disorder questionnaire. Am J Psychiat 157:1873–1875

    Article  CAS  PubMed  Google Scholar 

  29. Hogan PS, Galaro JK, Chib V (2019) Roles of ventromedial prefrontal cortex and anterior cingulate in subjective valuation of prospective effort. Cereb Cortex 29:4277–4290

    Article  PubMed  Google Scholar 

  30. Huang J, Yang XH, Lan Y, Zhu CY, Liu XQ, Wang YF, Cheung EF, Xie GR, Chan RC (2016) Neural substrates of the impaired effort expenditure decision making in schizophrenia. Neuropsychology 30:685–696

    Article  PubMed  Google Scholar 

  31. Insel T, Cuthbert B, Garvey M, Heinssen R, Pine DS, Quinn K, Sanislow C, Wang P (2010) Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am J Psychiat 167:748–751

    Article  PubMed  Google Scholar 

  32. Johnson SL, Edge MD, Holmes MK, Carver CS (2012) The behavioral activation system and mania. Annu Rev Clin Psychol 8:243

    Article  PubMed  Google Scholar 

  33. Kay SR, Fiszbein A, Opler LA (1987) The positive and negative syndrome scale (panss) for schizophrenia. Schizophr Bull 13:261–276

    Article  CAS  PubMed  Google Scholar 

  34. Knutson B, Bhanji JP, Cooney RE, Atlas LY, Gotlib IH (2008) Neural responses to monetary incentives in major depression. Biol Psychiatry 63:686–692

    Article  PubMed  Google Scholar 

  35. Kring AM, Barch DM (2014) The motivation and pleasure dimension of negative symptoms: neural substrates and behavioral outputs. Eur Neuropsychopharmacol 24:725–736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Kwapil TR (1998) Social anhedonia as a predictor of the development of schizophrenia-spectrum disorders. J Abnorm Psychol 107:558–565

    Article  CAS  PubMed  Google Scholar 

  37. Li Z, Yan C, Lv Q-y, Yi Z-h, Zhang J-y, Wang J-h, Lui SSY, Xu Y-f, Cheung EFC, Gur RE, Gur RC, Chan RCK (2018) Striatal dysfunction in patients with schizophrenia and their unaffected first-degree relatives. Schizophr Res 195:215–221

    Article  PubMed  Google Scholar 

  38. Morris R, Griffiths O, Le Pelley ME, Weickert TW (2013) Attention to irrelevant cues is related to positive symptoms in schizophrenia. Schizophr Bull 39:575–582

    Article  PubMed  Google Scholar 

  39. Morris RW, Vercammen A, Lenroot R, Moore L, Langton JM, Short B, Kulkarni J, Curtis J, O’Donnell M, Weickert CS, Weickert TW (2012) Disambiguating ventral striatum fmri-related bold signal during reward prediction in schizophrenia. Mol Psychiatry 17:280–289

    Article  Google Scholar 

  40. Nusslock R, Almeida JR, Forbes EE, Versace A, Frank E, Labarbara EJ, Klein CR, Phillips ML (2012) Waiting to win: elevated striatal and orbitofrontal cortical activity during reward anticipation in euthymic bipolar disorder adults. Bipolar Disord 14:249–260

    Article  PubMed  Google Scholar 

  41. Satterthwaite TD, Kable JW, Vandekar L, Katchmar N, Bassett DS, Baldassano CF, Ruparel K, Elliott MA, Sheline YI, Gur RC (2015) Common and dissociable dysfunction of the reward system in bipolar and unipolar depression. Neuropsychopharmacology. https://doi.org/10.1038/npp.2015.75

    Article  PubMed  PubMed Central  Google Scholar 

  42. Seo H, Lee D (2007) Temporal filtering of reward signals in the dorsal anterior cingulate cortex during a mixed-strategy game. J Neurosci 27:8366–8377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Sharma A, Wolf DH, Ciric R, Kable JW, Moore TM, Vandekar SN, Katchmar N, Daldal A, Ruparel K, Davatzikos C (2017) Common dimensional reward deficits across mood and psychotic disorders: a connectome-wide association study. Am J Psychiat 174:657–666

    Article  PubMed  Google Scholar 

  44. Sheehan D, Janavs J, Harnett-Sheehan K, Sheehan M, Gray C, Lecrubier Y (2009). MINI: Mini international neuropsychiatric interview english version 6.0. 0 DSM-IV. Website: http://www.psy.uwa.edu.au/user/andrew/MINI600.pdf. Accessed 1.

  45. Smoski MJ, Felder J, Bizzell J, Green SR, Ernst M, Lynch TR, Dichter GS (2009) fMRI of alterations in reward selection, anticipation, and feedback in major depressive disorder. J Affect Disord 118:69–78

    Article  PubMed  PubMed Central  Google Scholar 

  46. Soder HE, Cooper JA, Lopez-Gamundi P, Hoots JK, Nunez C, Lawlor VM, Lane SD, Treadway MT, Wardle MC (2020) Dose-response effects of d-amphetamine on effort-based decision-making and reinforcement learning. Neuropsychopharmacology. https://doi.org/10.1038/s41386-020-0779-8

    Article  PubMed  PubMed Central  Google Scholar 

  47. Strauss GP, Esfahlani FZ, Kirkpatrick B, Allen DN, Gold JM, Visser KF, Sayama H (2019) Network analysis reveals which negative symptom domains are most central in schizophrenia vs bipolar disorder. Schizophr Bull 45:1319–1330

    Article  PubMed  PubMed Central  Google Scholar 

  48. Strauss GP, Gold JM (2012) A new perspective on anhedonia in schizophrenia. Am J Psychiat 169:364–373

    Article  PubMed  Google Scholar 

  49. Treadway MT, Bossaller NA, Shelton RC, Zald DH (2012) Effort-based decision-making in major depressive disorder: a translational model of motivational anhedonia. J Abnorm Psychol 121:553–558

    Article  PubMed  PubMed Central  Google Scholar 

  50. Treadway MT, Buckholtz JW, Schwartzman AN, Lambert WE, Zald DH (2009) Worth the ‘eefrt’? The effort expenditure for rewards task as an objective measure of motivation and anhedonia. PLoS ONE 4:e6598

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Treadway MT, Peterman JS, Zald DH, Park S (2015) Impaired effort allocation in patients with schizophrenia. Schizophr Res 161:382–385

    Article  PubMed  Google Scholar 

  52. Treadway MT, Zald DH (2013) Parsing anhedonia: translational models of reward-processing deficits in psychopathology. Curr Dir Psychol Sci 22:244–249

    Article  PubMed  PubMed Central  Google Scholar 

  53. Treadway MT, Zald DH (2011) Reconsidering anhedonia in depression: lessons from translational neuroscience. Neurosci Biobehav Rev 35:537–555

    Article  PubMed  Google Scholar 

  54. Wang YY, Ge MH, Zhu GH, Jiang NZ, Wang GZ, Lv SX, Zhang Q, Guo JN, Tian X, Lui SSY, Cheung EFC, Heerey EA, Sun HW, Chan RCK (2020) Emotion-behavior decoupling in individuals with schizophrenia, bipolar disorder, and major depressive disorder. J Abnorm Psychol 129:331–342

    Article  PubMed  Google Scholar 

  55. Webb JR, Schroeder MI, Chee C, Dial D, Hana R, Jefee H, Mays J, Molitor P (2013) Left-handedness among a community sample of psychiatric outpatients suffering from mood and psychotic disorders. SAGE Open 3:1–5

    Google Scholar 

  56. Whitton AE, Treadway MT, Pizzagalli DA (2015) Reward processing dysfunction in major depression, bipolar disorder and schizophrenia. Curr Opin Psychiatry 28:7–12

    Article  PubMed  PubMed Central  Google Scholar 

  57. Yan CG, Wang XD, Zuo XN, Zang YF (2016) Dpabi: data processing and analysis for (resting-state) brain imaging. Neuroinformatics 14:339–351

    Article  PubMed  Google Scholar 

  58. Yang XH, Huang J, Lan Y, Zhu CY, Liu XQ, Wang YF, Cheung EFC, Xie GR, Chan RCK (2016) Diminished caudate and superior temporal gyrus responses to effort-based decision making in patients with first-episode major depressive disorder. Neuropsychopharmacol Biol Psychiatry 64:52–59

    Article  Google Scholar 

  59. Zou Y, Ni K, Wang Y, Yu E, Lui S, Zhou F, Yang H, Cohen A, Strauss G, Cheung E (2020) Effort–cost computation in a transdiagnostic psychiatric sample: differences among patients with schizophrenia, bipolar disorder, and major depressive disorder. PsyCh J 9:210–222

    Article  PubMed  Google Scholar 

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Acknowledgements

This study was supported by a grant from the National Key Research and Development Programme (2016YFC0906402), the National Science Fund China (81571317), the Beijing Municipal Science & Technology Commission Grant (Z161100000216138), the Beijing Training Project for the Leading Talents in Science and Technology (Z151100000315020), the Philip K. H. Wong Foundation, and the CAS Key Laboratory of Mental Health, Institute of Psychology to Raymond Chan; the National Science Fund China (31871114), and the CAS Key Laboratory of Mental Health, Institute of Psychology to Yi Wang; the Natural Science Foundation of Shandong Province (ZR2017LC023, ZR2017MH110), and the Humanities and Social Sciences Research Project of Ministry of Education (19YJA190006) to Yan-yu Wang.

Funding

This study was supported by a grant from the National Key Research and Development Programme (2016YFC0906402), the National Science Fund China (81571317), the Beijing Municipal Science & Technology Commission Grant (Z161100000216138), the Beijing Training Project for the Leading Talents in Science and Technology (Z151100000315020), the Philip K. H. Wong Foundation, and the CAS Key Laboratory of Mental Health, Institute of Psychology to Raymond Chan; the National Science Fund China (31871114), and the CAS Key Laboratory of Mental Health, Institute of Psychology to Yi Wang; the Natural Science Foundation of Shandong Province (ZR2017LC023, ZR2017MH110), and the Humanities and Social Sciences Research Project of Ministry of Education (19YJA190006) to Yan-yu Wang.

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Authors and Affiliations

  1. School of Psychology, Weifang Medical University, Shandong, 261053, China

    Yan-yu Wang & Hong-wei Sun

  2. Neuropsychology and Applied Cognitive Neuroscience Laboratory; CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, 16 Lincui Road, Beijing, 100101, China

    Yan-yu Wang, Yi Wang, Jia Huang & Raymond C. K. Chan

  3. Department of Psychology, University of Chinese Academy of Sciences, Beijing, 100048, China

    Yi Wang, Jia Huang & Raymond C. K. Chan

  4. Magnetic Resonance Imaging Centre, Affiliated Hospital of Weifang Medical University, Shandong, 261031, China

    Xi-he Sun, Xi-zhen Wang & Shu-xian Zhang

  5. Mental Health Centre of Weifang City, Shandong, 261071, China

    Guo-hui Zhu

  6. Department of Psychiatry, The University of Hong Kong, Hong Kong Special Administrative Region, China

    Simon S. Y. Lui

  7. Castle Peak Hospital, Hong Kong Special Administrative Region, China

    Eric F. C. Cheung

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  1. Yan-yu Wang
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  3. Jia Huang
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Contributions

YYW designed the study, collected, analyzed the data, and wrote up the first draft of the manuscript. YW and HJ analyzed and interpreted the data and commented critically to the manuscript. XHS, XZW, and SXZ set the parameters and collected the imaging data. GHZ administered clinical rating for patients. SSYL, EFC, and HWS commented critically to the manuscript. RCKC generated the idea, designed the study, interpreted the data, and commented critically to the manuscript. All authors contributed to and have approved the final manuscript.

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Correspondence to Raymond C. K. Chan.

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Wang, Yy., Wang, Y., Huang, J. et al. Shared and distinct reward neural mechanisms among patients with schizophrenia, major depressive disorder, and bipolar disorder: an effort-based functional imaging study. Eur Arch Psychiatry Clin Neurosci 272, 859–871 (2022). https://doi.org/10.1007/s00406-021-01376-3

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