The Neurobiology of Motivational Deficits in Depression—An Update on Candidate Pathomechanisms

  • Michael T. Treadway
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 27)


Anhedonia has long been recognized as a central feature of major depression, yet its neurobiological underpinnings remain poorly understood. While clinical definitions of anhedonia have historically emphasized reductions in pleasure and positive emotionality, there has been growing evidence that motivation may be substantially impaired as well. Here, we review recent evidence suggesting that motivational deficits may reflect an important dimension of symptomatology that is discrete from traditional definitions of anhedonia in terms of both behavior and pathophysiology. In summarizing this work, we highlight two candidate neurobiological mechanisms—elevated inflammation and reduced synaptic plasticity—that may underlie observed reductions in motivation and reinforcement learning in depression.


Depression Motivation Effort-based decision-making Reinforcement learning Dopamine Inflammation Neuroplasticity 


Acknowledgements and Disclosures

The author wishes to thank Amanda Arulpragasam for helpful comments. The author declares no conflict of interest, financial or otherwise. The author has served as a paid consultant to Avanir Pharmaceuticals and the Boston Consulting Group. No funding or sponsorship was provided by these companies for the current work, and all views expressed herein are solely those of author.


  1. Agren H, Reibring L (1994) PET studies of presynaptic monoamine metabolism in depressed patients and healthy volunteers. Pharmacopsychiatry 27(1):2–6PubMedCrossRefGoogle Scholar
  2. Amsterdam JD, Newberg AB (2007) A preliminary study of dopamine transporter binding in bipolar and unipolar depressed patients and healthy controls. Neuropsychobiology 55(3–4):167–170PubMedCrossRefGoogle Scholar
  3. Autry AE, Adachi M, Nosyreva E, Na ES, Los MF, Cheng P-F, Kavalali ET, Monteggia LM (2011) NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature 475(7354):91–95PubMedPubMedCentralCrossRefGoogle Scholar
  4. Autry AE, Monteggia LM (2012) Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacol Rev 64(2):238–258PubMedPubMedCentralCrossRefGoogle Scholar
  5. Barch DM, Dowd EC (2010) Goal representations and motivational drive in schizophrenia: the role of prefrontal-striatal interactions. Schizophr Bull 36(5):919–934PubMedPubMedCentralCrossRefGoogle Scholar
  6. Bardgett ME, Depenbrock M, Downs N, Points M, Green L (2009) Dopamine modulates effort-based decision making in rats. Behav Neurosci 123(2):242–251PubMedPubMedCentralCrossRefGoogle Scholar
  7. Beierholm U, Guitart-Masip M, Economides M, Chowdhury R, Düzel E, Dolan R, Dayan P (2013) Dopamine modulates reward-related vigor. Neuropsychopharmacology 38:1495–1503PubMedPubMedCentralCrossRefGoogle Scholar
  8. Berridge KC, Kringelbach ML (2008) Affective neuroscience of pleasure: reward in humans and animals. Psychopharmacology 199(3):457–480PubMedPubMedCentralCrossRefGoogle Scholar
  9. Blume J, Douglas SD, Evans DL (2011) Immune suppression and immune activation in depression. Brain Behav Immun 25(2):221–229PubMedPubMedCentralCrossRefGoogle Scholar
  10. Bragulat V, Paillere-Martinot ML, Artiges E, Frouin V, Poline JB, Martinot JL (2007) Dopaminergic function in depressed patients with affective flattening or with impulsivity: [18F]fluoro-L-dopa positron emission tomography study with voxel-based analysis. Psychiatry Res 154(2):115–124PubMedCrossRefGoogle Scholar
  11. Bus B, Molendijk M, Tendolkar I, Penninx B, Prickaerts J, Elzinga B, Voshaar R (2015) Chronic depression is associated with a pronounced decrease in serum brain-derived neurotrophic factor over time. Mol Psychiatry 20(5):602–608PubMedCrossRefGoogle Scholar
  12. Cannon DM, Klaver JM, Peck SA, Rallis-Voak D, Erickson K, Drevets WC (2009) Dopamine type-1 receptor binding in major depressive disorder assessed using positron emission tomography and [11C]NNC-112. Neuropsychopharmacology 34(5):1277–1287PubMedPubMedCentralCrossRefGoogle Scholar
  13. Capuron L, Miller AH (2011) Immune system to brain signaling: neuropsychopharmacological implications. Pharmacol Ther 130(2):226–238PubMedPubMedCentralCrossRefGoogle Scholar
  14. Capuron L, Pagnoni G, Demetrashvili MF, Lawson DH, Fornwalt FB, Woolwine B, Berns GS, Nemeroff CB, Miller AH (2007) Basal ganglia hypermetabolism and symptoms of fatigue during interferon-alpha therapy. Neuropsychopharmacology 32(11):2384–2392PubMedCrossRefGoogle Scholar
  15. Capuron L, Pagnoni G, Drake DF, Woolwine BJ, Spivey JR, Crowe RJ, Votaw JR, Goodman MM, Miller AH (2012) Dopaminergic mechanisms of reduced Basal Ganglia responses to hedonic reward during interferon alfa administration. Arch Gen Psychiatry 69(10):1044–1053PubMedPubMedCentralCrossRefGoogle Scholar
  16. Capuron L, Ravaud A, Miller AH, Dantzer R (2004) Baseline mood and psychosocial characteristics of patients developing depressive symptoms during interleukin-2 and/or interferon-alpha cancer therapy. Brain Behav Immun 18(3):205–213PubMedCrossRefGoogle Scholar
  17. Chana G, Landau S, Beasley C, Everall IP, Cotter D (2003) Two-dimensional assessment of cytoarchitecture in the anterior cingulate cortex in major depressive disorder, bipolar disorder, and schizophrenia: evidence for decreased neuronal somal size and increased neuronal density. Biol Psychiatry 53(12):1086–1098PubMedCrossRefGoogle Scholar
  18. Cotter D, Mackay D, Landau S, Kerwin R, Everall I (2001) Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder. Arch Gen Psychiatry 58(6):545–553PubMedCrossRefGoogle Scholar
  19. Couch Y, Anthony DC, Dolgov O, Revischin A, Festoff B, Santos AI, Steinbusch HW, Strekalova T (2013) Microglial activation, increased TNF and SERT expression in the prefrontal cortex define stress-altered behaviour in mice susceptible to anhedonia. Brain Behav Immun 29:136–146PubMedCrossRefGoogle Scholar
  20. Cousins MS, Salamone JD (1994) Nucleus accumbens dopamine depletions in rats affect relative response allocation in a novel cost/benefit procedure. Pharmacol Biochem Behav 49(1):85–91PubMedCrossRefGoogle Scholar
  21. Croxson PL, Walton ME, O’Reilly JX, Behrens TE, Rushworth MF (2009) Effort-based cost-benefit valuation and the human brain. J Neurosci 29(14):4531–4541PubMedPubMedCentralCrossRefGoogle Scholar
  22. D’Ardenne K, Nystrom LE, Cohen JD (2008) BOLD responses reflecting dopaminergic signals in the human ventral tegmental area. Science 5867(319):1264–1267Google Scholar
  23. D’Haenen HA, Bossuyt A (1994) Dopamine D2 receptors in depression measured with single photon emission computed tomography. Biol Psychiatry 35(2):128–132PubMedCrossRefGoogle Scholar
  24. Dantzer R, Meagher MW, Cleeland CS (2012) Translational approaches to treatment-induced symptoms in cancer patients. Nat Rev Clin Oncol 9(7):414–426PubMedPubMedCentralCrossRefGoogle Scholar
  25. Diazgranados N, Ibrahim L, Brutsche NE, Newberg A, Kronstein P, Khalife S, Kammerer WA, Quezado Z, Luckenbaugh DA, Salvadore G, Machado-Vieira R, Manji HK, Zarate CA Jr (2010) A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression. Arch Gen Psychiatry 67(8):793–802PubMedPubMedCentralCrossRefGoogle Scholar
  26. Dickens C, Creed F (2001) The burden of depression in patients with rheumatoid arthritis. Rheumatology 40(12):1327–1330PubMedCrossRefGoogle Scholar
  27. Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctot KL (2010) A meta-analysis of cytokines in major depression. Biol Psychiatry 67(5):446–457PubMedCrossRefGoogle Scholar
  28. Duman RS, Aghajanian GK (2012) Synaptic dysfunction in depression: potential therapeutic targets. Science 338(6103):68–72PubMedPubMedCentralCrossRefGoogle Scholar
  29. Dwivedi Y, Rizavi HS, Conley R, Pandey G (2005) ERK MAP kinase signaling in post-mortem brain of suicide subjects: differential regulation of upstream Raf kinases Raf-1 and B-Raf. Mol Psychiatry 11(1):86–98CrossRefGoogle Scholar
  30. Eisenberger NI, Berkman ET, Inagaki TK, Rameson LT, Mashal NM, Irwin MR (2010) Inflammation-induced anhedonia: endotoxin reduces ventral striatum responses to reward. Biol Psychiatry 68(8):748–754PubMedPubMedCentralCrossRefGoogle Scholar
  31. Felger JC, Alagbe O, Hu F, Mook D, Freeman AA, Sanchez MM, Kalin NH, Ratti E, Nemeroff CB, Miller AH (2007) Effects of interferon-alpha on rhesus monkeys: a nonhuman primate model of cytokine-induced depression. Biol Psychiatry 62(11):1324–1333PubMedPubMedCentralCrossRefGoogle Scholar
  32. Felger JC, Miller AH (2014) Cytokine effects on the basal ganglia and dopamine function: the subcortical source of inflammatory malaise. Front NeuroendocrinolGoogle Scholar
  33. Felger JC, Mun J, Kimmel HL, Nye JA, Drake DF, Hernandez CR, Freeman AA, Rye DB, Goodman MM, Howell LL (2013) Chronic interferon-α decreases dopamine 2 receptor binding and striatal dopamine release in association with anhedonia-like behavior in nonhuman primates. Neuropsychopharmacology 38(11):2179–2187PubMedPubMedCentralCrossRefGoogle Scholar
  34. Floresco SB (2015) The nucleus accumbens: an interface between cognition, emotion, and action. Annu Rev Psychol 66:25–52PubMedCrossRefGoogle Scholar
  35. Foussias G, Remington G (2008) Negative symptoms in schizophrenia: avolition and Occam’s razor. Schizophr Bull 36(2):359–369PubMedPubMedCentralCrossRefGoogle Scholar
  36. Frank MJ, O’Reilly RC (2006) A mechanistic account of striatal dopamine function in human cognition: psychopharmacological studies with cabergoline and haloperidol. Behav Neurosci 120(3):497PubMedCrossRefGoogle Scholar
  37. Frank MJ, Seeberger LC, O’Reilly RC (2004) By carrot or by stick: cognitive reinforcement learning in parkinsonism. Science 306(5703):1940–1943PubMedCrossRefGoogle Scholar
  38. Gershon AA, Vishne T, Grunhaus L (2007) Dopamine D2-like receptors and the antidepressant response. Biol Psychiatry 61(2):145–153PubMedCrossRefGoogle Scholar
  39. Gold JM, Waltz JA, Prentice KJ, Morris SE, Heerey EA (2008) Reward processing in schizophrenia: a deficit in the representation of value. Schizophr Bull 34(5):835–847PubMedPubMedCentralCrossRefGoogle Scholar
  40. Haber SN, Knutson B (2010) The reward circuit: linking primate anatomy and human imaging. Neuropsychopharmacology 35(1):4–26PubMedPubMedCentralCrossRefGoogle Scholar
  41. Harrison NA, Brydon L, Walker C, Gray MA, Steptoe A, Critchley HD (2009) Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity. Biol Psychiatry 66(5):407–414PubMedPubMedCentralCrossRefGoogle Scholar
  42. Hart AS, Rutledge RB, Glimcher PW, Phillips PEM (2014) Phasic dopamine release in the rat nucleus accumbens symmetrically encodes a reward prediction error term. J Neurosci 34(3):698–704PubMedPubMedCentralCrossRefGoogle Scholar
  43. Hartmann MN, Hager OM, Tobler PN, Kaiser S (2013) Parabolic discounting of monetary rewards by physical effort. Behav Process 100:192–196CrossRefGoogle Scholar
  44. Hirvonen J, Karlsson H, Kajander J, Markkula J, Rasi-Hakala H, Nagren K, Salminen JK, Hietala J (2008) Striatal dopamine D2 receptors in medication-naive patients with major depressive disorder as assessed with [11C]raclopride PET. Psychopharmacology 197(4):581–590PubMedCrossRefGoogle Scholar
  45. Howren MB, Lamkin DM, Suls J (2009) Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med 71(2):171–186PubMedCrossRefGoogle Scholar
  46. Ibrahim L, Diazgranados N, Luckenbaugh DA, Machado-Vieira R, Baumann J, Mallinger AG, Zarate CA Jr (2011) Rapid decrease in depressive symptoms with an N-methyl-d-aspartate antagonist in ECT-resistant major depression. Prog Neuropsychopharmacol Biol Psychiatry 35(4):1155–1159PubMedPubMedCentralCrossRefGoogle Scholar
  47. 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 Psychiatry 167(7):748–751PubMedCrossRefGoogle Scholar
  48. Insel TR, Cuthbert BN (2015) Brain disorders? Precisely. Science 348(6234):499–500PubMedCrossRefGoogle Scholar
  49. Kempermann G, Kronenberg G (2003) Depressed new neurons?, Adult hippocampal neurogenesis and a cellular plasticity hypothesis of major depression. Biol Psychiatry 54(5):499–503PubMedCrossRefGoogle Scholar
  50. Kempton MJ, Salvador Z, Munafo MR, Geddes JR, Simmons A, Frangou S, Williams SC (2011) Structural neuroimaging studies in major depressive disorder. Meta-analysis and comparison with bipolar disorder. Arch Gen Psychiatry 68(7):675–690PubMedCrossRefGoogle Scholar
  51. Klein DF (1974) Endogenomorphic depression. A conceptual and terminological revision. Arch Gen Psychiatry 31(4):447–454PubMedCrossRefGoogle Scholar
  52. Klein DN (1987) Depression and Anhedonia. Anhedonia Affect Deficit States 31:1–14Google Scholar
  53. Klimek V, Schenck JE, Han H, Stockmeier CA, Ordway GA (2002) Dopaminergic abnormalities in amygdaloid nuclei in major depression: a postmortem study. Biol Psychiatry 52(7):740–748PubMedCrossRefGoogle Scholar
  54. Klimke A, Larisch R, Janz A, Vosberg H, Muller-Gartner HW, Gaebel W (1999) Dopamine D2 receptor binding before and after treatment of major depression measured by [123I]IBZM SPECT. Psychiatry Res 90(2):91–101PubMedCrossRefGoogle Scholar
  55. Kravitz AV, Tye LD, Kreitzer AC (2012) Distinct roles for direct and indirect pathway striatal neurons in reinforcement. Nat Neurosci 15(6):816–818PubMedPubMedCentralCrossRefGoogle Scholar
  56. Kumar P, Waiter G, Ahearn T, Milders M, Reid I, Steele JD (2008) Abnormal temporal difference reward-learning signals in major depression. Brain 131(Pt 8):2084–2093PubMedCrossRefGoogle Scholar
  57. Kurniawan IT, Seymour B, Talmi D, Yoshida W, Chater N, Dolan RJ (2010) Choosing to make an effort: the role of striatum in signaling physical effort of a chosen action. J Neurophysiol 104(1):313–321PubMedPubMedCentralCrossRefGoogle Scholar
  58. Laasonen-Balk T, Kuikka J, Viinamaki H, Husso-Saastamoinen M, Lehtonen J, Tiihonen J (1999) Striatal dopamine transporter density in major depression. Psychopharmacology 144(3):282–285PubMedCrossRefGoogle Scholar
  59. Lotrich FE, Albusaysi S, Ferrell RE (2013) Brain-derived neurotrophic factor serum levels and genotype: association with depression during interferon-α treatment. Neuropsychopharmacology 38(6):985–995PubMedPubMedCentralCrossRefGoogle Scholar
  60. MacQueen GM, Campbell S, McEwen BS, Macdonald K, Amano S, Joffe RT, Nahmias C, Young LT (2003) Course of illness, hippocampal function, and hippocampal volume in major depression. Proc Natl Acad Sci 100(3):1387–1392PubMedPubMedCentralCrossRefGoogle Scholar
  61. Martinot M, Bragulat V, Artiges E, Dolle F, Hinnen F, Jouvent R, Martinot J (2001) Decreased presynaptic dopamine function in the left caudate of depressed patients with affective flattening and psychomotor retardation. Am J Psychiatry 158(2):314–316PubMedCrossRefGoogle Scholar
  62. McGuire JT, Botvinick MM (2010) Prefrontal cortex, cognitive control, and the registration of decision costs. Proc Natl Acad Sci USA 107(17):7922–7926PubMedPubMedCentralCrossRefGoogle Scholar
  63. Meehl PE (1975) Hedonic capacity: some conjectures. Bull Menninger Clin 39(4):295–307PubMedGoogle Scholar
  64. Meyer JH, Kruger S, Wilson AA, Christensen BK, Goulding VS, Schaffer A, Minifie C, Houle S, Hussey D, Kennedy SH (2001) Lower dopamine transporter binding potential in striatum during depression. NeuroReport 12(18):4121–4125PubMedCrossRefGoogle Scholar
  65. Miller AH, Maletic V, Raison CL (2009a) Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry 65(9):732–741PubMedPubMedCentralCrossRefGoogle Scholar
  66. Miller AH, Maletic V, Raison CL (2009b) Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry 65(9):732–741PubMedPubMedCentralCrossRefGoogle Scholar
  67. Molendijk M, Spinhoven P, Polak M, Bus B, Penninx B, Elzinga B (2014) Serum BDNF concentrations as peripheral manifestations of depression: evidence from a systematic review and meta-analyses on 179 associations (N= 9484). Mol Psychiatry 19(7):791–800PubMedCrossRefGoogle Scholar
  68. Monje ML, Toda H, Palmer TD (2003) Inflammatory blockade restores adult hippocampal neurogenesis. Science 302(5651):1760–1765PubMedCrossRefGoogle Scholar
  69. Monkul E, Hatch JP, Nicoletti MA, Spence S, Brambilla P, Lacerda AL, Sassi RB, Mallinger A, Keshavan M, Soares JC (2006) Fronto-limbic brain structures in suicidal and non-suicidal female patients with major depressive disorder. Mol Psychiatry 12(4):360–366PubMedCrossRefGoogle Scholar
  70. Monteggia LM, Zarate C (2015) Antidepressant actions of ketamine: from molecular mechanisms to clinical practice. Curr Opin Neurobiol 30:139–143PubMedPubMedCentralCrossRefGoogle Scholar
  71. Murrough JW, Iosifescu DV, Chang LC, Al Jurdi RK, Green CE, Perez AM, Iqbal S, Pillemer S, Foulkes A, Shah A, Charney DS, Mathew SJ (2013a) Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry 170(10):1134–1142PubMedPubMedCentralCrossRefGoogle Scholar
  72. Murrough JW, Perez AM, Pillemer S, Stern J, Parides MK, aan het Rot M, Collins KA, Mathew SJ, Charney DS, Iosifescu DV (2013b) Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression. Biol Psychiatry 74(4):250–256PubMedPubMedCentralCrossRefGoogle Scholar
  73. Nunes EJ, Randall PA, Estrada A, Epling B, Hart EE, Lee CA, Baqi Y, Mueller CE, Correa M, Salamone JD (2013) Effort-related motivational effects of the pro-inflammatory cytokine interleukin 1-beta: studies with the concurrent fixed ratio 5/chow feeding choice task. Psychopharmacology 1–10Google Scholar
  74. Parsey RV, Oquendo MA, Zea-Ponce Y, Rodenhiser J, Kegeles LS, Pratap M, Cooper TB, Van Heertum R, Mann JJ, Laruelle M (2001) Dopamine D(2) receptor availability and amphetamine-induced dopamine release in unipolar depression. Biol Psychiatry 50(5):313–322PubMedCrossRefGoogle Scholar
  75. Pessiglione M, Schmidt L, Draganski B, Kalisch R, Lau H, Dolan RJ, Frith CD (2007) How the brain translates money into force: a neuroimaging study of subliminal motivation. Science 316(5826):904–906PubMedPubMedCentralCrossRefGoogle Scholar
  76. Pessiglione M, Seymour B, Flandin G, Dolan RJ, Frith CD (2006) Dopamine-dependent prediction errors underpin reward-seeking behaviour in humans. Nature 442(7106):1042–1045PubMedPubMedCentralCrossRefGoogle Scholar
  77. Pincus T, Griffith J, Pearce S, Isenberg D (1996) Prevalence of self-reported depression in patients with rheumatoid arthritis. Br J Rheumatol 35(9):879–883PubMedCrossRefGoogle Scholar
  78. Pittenger C, Duman RS (2007) Stress, depression, and neuroplasticity: a convergence of mechanisms. Neuropsychopharmacology 33(1):88–109PubMedCrossRefGoogle Scholar
  79. Pizzagalli DA, Holmes AJ, Dillon DG, Goetz EL, Birk JL, Bogdan R, Dougherty DD, Iosifescu DV, Rauch SL, Fava M (2009) Reduced caudate and nucleus accumbens response to rewards in unmedicated individuals with major depressive disorder. Am J Psychiatry 166(6):702–710PubMedPubMedCentralCrossRefGoogle Scholar
  80. Pizzagalli DA, Iosifescu D, Hallett LA, Ratner KG, Fava M (2008) Reduced hedonic capacity in major depressive disorder: evidence from a probabilistic reward task. J Psychiatr Res 43(1):76–87PubMedPubMedCentralCrossRefGoogle Scholar
  81. Prevost C, Pessiglione M, Metereau E, Clery-Melin ML, Dreher JC (2010) Separate valuation subsystems for delay and effort decision costs. J Neurosci 30(42):14080–14090PubMedCrossRefGoogle Scholar
  82. Qin L, Wu X, Block ML, Liu Y, Breese GR, Hong JS, Knapp DJ, Crews FT (2007) Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia 55(5):453–462PubMedPubMedCentralCrossRefGoogle Scholar
  83. Rahmim A, Zaidi H (2008) PET versus SPECT: strengths, limitations and challenges. Nucl Med Commun 29(3):193–207PubMedCrossRefGoogle Scholar
  84. Raison CL, Miller AH (2011) Is depression an inflammatory disorder? Current Psychiatry Reports 13(6):467–475PubMedPubMedCentralCrossRefGoogle Scholar
  85. Raison CL, Rutherford RE, Woolwine BJ, Shuo C, Schettler P, Drake DF, Haroon E, Miller AH (2013) A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression. JAMA Psychiatry 70(1):31–41PubMedPubMedCentralCrossRefGoogle Scholar
  86. Reynolds JN, Hyland BI, Wickens JR (2001) A cellular mechanism of reward-related learning. Nature 413(6851):67–70PubMedCrossRefGoogle Scholar
  87. Ribot T (1896) La psychologie des sentiment (The psychology of feelings). Felix Alcan, ParisGoogle Scholar
  88. Rushworth MF, Noonan MP, Boorman ED, Walton ME, Behrens TE (2011) Frontal cortex and reward-guided learning and decision-making. Neuron 70(6):1054–1069PubMedCrossRefGoogle Scholar
  89. Salamone JD, Correa M, Farrar A, Mingote SM (2007) Effort-related functions of nucleus accumbens dopamine and associated forebrain circuits. Psychopharmacology 191(3):461–482PubMedCrossRefGoogle Scholar
  90. Salamone JD, Cousins MS, Bucher S (1994) Anhedonia or anergia? Effects of haloperidol and nucleus accumbens dopamine depletion on instrumental response selection in a T-maze cost/benefit procedure. Behav Brain Res 65(2):221–229PubMedCrossRefGoogle Scholar
  91. Sarchiapone M, Carli V, Camardese G, Cuomo C, Di Giuda D, Calcagni ML, Focacci C, De Risio S (2006) Dopamine transporter binding in depressed patients with anhedonia. Psychiatry Res 147(2–3):243–248PubMedCrossRefGoogle Scholar
  92. Sarkar C, Basu B, Chakroborty D, Dasgupta PS, Basu S (2010) The immunoregulatory role of dopamine: an update. Brain Behav Immun 24(4):525–528PubMedPubMedCentralCrossRefGoogle Scholar
  93. Schmaal L, Veltman DJ, van Erp TG, Sämann P, Frodl T, Jahanshad N, Loehrer E, Tiemeier H, Hofman A, Niessen W (2015) Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group. Molecular PsychiatryGoogle Scholar
  94. Schmidt L, Lebreton M, Clery-Melin ML, Daunizeau J, Pessiglione M (2012) Neural mechanisms underlying motivation of mental versus physical effort. PLoS Biol 10(2):e1001266PubMedPubMedCentralCrossRefGoogle Scholar
  95. Schultz W (2007) Multiple dopamine functions at different time courses. Annu Rev Neurosci 30:259–288PubMedCrossRefGoogle Scholar
  96. Shah PJ, Ogilvie AD, Goodwin GM, Ebmeier KP (1997) Clinical and psychometric correlates of dopamine D2 binding in depression. Psychol Med 27(6):1247–1256PubMedCrossRefGoogle Scholar
  97. Sharot T, Shiner T, Brown AC, Fan J, Dolan RJ (2009) Dopamine enhances expectation of pleasure in humans. Curr Biol 19(24):2077–2080PubMedPubMedCentralCrossRefGoogle Scholar
  98. Sheline YI, Sanghavi M, Mintun MA, Gado MH (1999) Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. J Neurosci 19(12):5034–5043PubMedGoogle Scholar
  99. Shelton RC, Tomarken AJ (2001) Can recovery from depression be achieved? Psychiatr Serv 52(11):1469–1478PubMedCrossRefGoogle Scholar
  100. Sherdell L, Waugh CE, Gotlib IH (2011) Anticipatory pleasure predicts motivation for reward in major depression. J Abnorm PsycholGoogle Scholar
  101. Simon NW, Beas BS, Montgomery KS, Haberman RP, Bizon JL, Setlow B (2013) Prefrontal cortical–striatal dopamine receptor mRNA expression predicts distinct forms of impulsivity. Eur J Neurosci 37:1779–1788Google Scholar
  102. Strauss GP, Gold JM (2012) A new perspective on anhedonia in Schizophrenia. Am J PsychiatryGoogle Scholar
  103. Sutton RS, Barto AG (1998) Reinforcement learning: an introduction. MIT Press, CambridgeGoogle Scholar
  104. Thorne R, Hanson L, Ross T, Tung D, Frey Ii W (2008) Delivery of interferon-β to the monkey nervous system following intranasal administration. Neuroscience 152(3):785–797PubMedCrossRefGoogle Scholar
  105. Treadway MT, Bossaller NA, Shelton RC, Zald DH (2012a) Effort-based decision-making in major depressive disorder: a translational model of motivational anhedonia. J Abnorm Psychol 121(3):553PubMedPubMedCentralCrossRefGoogle Scholar
  106. Treadway MT, Buckholtz JW, Cowan RL, Woodward ND, Li R, Ansari MS, Baldwin RM, Schwartzman AN, Kessler RM, Zald DH (2012b) Dopaminergic mechanisms of individual differences in human effort-based decision-making. J Neurosci 32(18):6170–6176PubMedPubMedCentralCrossRefGoogle Scholar
  107. 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(8):e6598PubMedPubMedCentralCrossRefGoogle Scholar
  108. Treadway MT, Pizzagalli DA (2014) Imaging the pathophysiology of major depressive disorder-from localist models to circuit-based analysis. Biol Mood Anxiety Disord 4(5)Google Scholar
  109. Treadway MT, Zald DH (2011) Reconsidering anhedonia in depression: lessons from translational neuroscience. Neurosci Biobehav Rev 35(3):537–555PubMedPubMedCentralCrossRefGoogle Scholar
  110. Treadway MT, Zald DH (2013) Parsing anhedonia translational models of reward-processing deficits in psychopathology. Curr Dir Psychol Sci 22(3):244–249PubMedPubMedCentralCrossRefGoogle Scholar
  111. Tsai HC, Zhang F, Adamantidis A, Stuber GD, Bonci A, de Lecea L, Deisseroth K (2009) Phasic firing in dopaminergic neurons is sufficient for behavioral conditioning. Science 324(5930):1080–1084PubMedCrossRefGoogle Scholar
  112. Vichaya EG, Hunt SC, Dantzer R (2014) Lipopolysaccharide Reduces incentive motivation while boosting preference for high reward in mice. NeuropsychopharmacologyGoogle Scholar
  113. Vrieze E, Ceccarini J, Pizzagalli DA, Bormans G, Vandenbulcke M, Demyttenaere K, Van Laere K, Claes S (2011) Measuring extrastriatal dopamine release during a reward learning task. Hum Brain MappGoogle Scholar
  114. Vrieze E, Pizzagalli DA, Demyttenaere K, Hompes T, Sienaert P, de Boer P, Schmidt M, Claes S (2013) Reduced reward learning predicts outcome in major depressive disorder. Biol PsychiatryGoogle Scholar
  115. Wardle MC, Treadway MT, Mayo LM, Zald DH, de Wit H (2011) Amping up effort: effects of d-amphetamine on human effort-based decision-making. J Neurosci 31(46):16597–16602PubMedPubMedCentralCrossRefGoogle Scholar
  116. Westbrook A, Kester D, Braver TS (2013) What is the subjective cost of cognitive effort? Load, trait, and aging effects revealed by economic preference. PLoS ONE 8(7):e68210PubMedPubMedCentralCrossRefGoogle Scholar
  117. Whitton AE, Treadway MT, Pizzagalli DA (2015) Reward processing dysfunction in major depression, bipolar disorder and schizophrenia. Curr Opin Psychiatry 28(1):7–12PubMedPubMedCentralCrossRefGoogle Scholar
  118. Wieland S, Schindler S, Huber C, Köhr G, Oswald MJ, Kelsch W (2015) Phasic dopamine modifies sensory-driven output of striatal neurons through synaptic plasticity. J Neurosci 35(27):9946–9956PubMedCrossRefGoogle Scholar
  119. Yan Y, Jiang W, Liu L, Wang X, Ding C, Tian Z, Zhou R (2015) Dopamine Controls Systemic Inflammation through Inhibition of NLRP3 Inflammasome. Cell 160(1):62–73PubMedCrossRefGoogle Scholar
  120. Yang X-H, Huang J, Zhu C-Y, Wang Y-F, Cheung EFC, Chan RCK, Xie G-R (2014) Motivational deficits in effort-based decision making in individuals with subsyndromal depression, first-episode and remitted depression patients. Psychiatry Res 220(3):874–882PubMedCrossRefGoogle Scholar
  121. Yang YK, Yeh TL, Yao WJ, Lee IH, Chen PS, Chiu NT, Lu RB (2008) Greater availability of dopamine transporters in patients with major depression–a dual-isotope SPECT study. Psychiatry Res 162(3):230–235PubMedCrossRefGoogle Scholar
  122. Yoshii A, Constantine-Paton M (2010) Postsynaptic BDNF-TrkB signaling in synapse maturation, plasticity, and disease. Dev Neurobiol 70(5):304–322PubMedPubMedCentralGoogle Scholar
  123. Zarate CA Jr, Brutsche NE, Ibrahim L, Franco-Chaves J, Diazgranados N, Cravchik A, Selter J, Marquardt CA, Liberty V, Luckenbaugh DA (2012) Replication of ketamine’s antidepressant efficacy in bipolar depression: a randomized controlled add-on trial. Biol Psychiatry 71(11):939–946PubMedPubMedCentralCrossRefGoogle Scholar
  124. Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK (2006) A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 63(8):856–864PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of PsychologyEmory UniversityAtlantaUSA

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