Current Treatment Options in Neurology

, Volume 9, Issue 5, pp 357–362 | Cite as

How schizophrenia and depression disrupt reward circuitry

  • Henry H. Holcomb
  • Laura M. Rowland
Psychiaric Manifestations of Neurologic Disease


Dopamine Schizophrenia Deep Brain Stimulation Anterior Cingulate Cortex Ventral Tegmental Area 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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References and Recommended Reading

  1. 1.
    Of major importance Berridge KC:The debate over dopamine’s role in reward: the case for incentive salience.Psychopharmacology (Berl) 2007,191:391–431. This is one of the most complete discussions available of this contentious and complicated issue. Although it is long, it is worth the time for serious students of this problem.CrossRefGoogle Scholar
  2. 2.
    Of importance Grace AA, Floresco SB, Goto Y, Lodge DJ:Regulation of firing of dopaminergic neurons and control of goal-directed behaviors.Trends Neurosci 2007,30:220–227. This is an excellent overview of dopamine physiology as it relates to goal-directed behavior, written by one of the leading investigators in this fast-moving field.PubMedCrossRefGoogle Scholar
  3. 3.
    Price JL:Subcortical projections from the amygdaloid complex.Adv Exp Med Biol 1986,203:19–33.PubMedGoogle Scholar
  4. 4.
    Price JL:Prefrontal cortical networks related to visceral function and mood.Ann N Y Acad Sci 1999,877:383–396.PubMedCrossRefGoogle Scholar
  5. 5.
    Cheer JF, Wassum KM, Heien ML, et al.:Cannabinoids enhance subsecond dopamine release in the nucleus accumbens of awake rats.J Neurosci 2004,24:4393–4400.PubMedCrossRefGoogle Scholar
  6. 6.
    Nestler EJ, Carlezon WA Jr:The mesolimbic dopamine reward circuit in depression.Biol Psychiatry 2006,59:1151–1159.PubMedCrossRefGoogle Scholar
  7. 7.
    Gur RC, Erwin RJ, Gur RE, et al.:Facial emotion discrimination: II. Behavioral findings in depression.Psychiatry Res 1992,42:241–251.PubMedCrossRefGoogle Scholar
  8. 8.
    Of importance Gur RE, Kohler CG, Ragland JD, et al.:Flat affect in schizophrenia: relation to emotion processing and neurocognitive measures.Schizophr Bull 2006,32:279–287. This is an especially thoughtful and careful assessment of emotional processing in schizophrenic volunteers.PubMedCrossRefGoogle Scholar
  9. 9.
    Laruelle M:Imaging dopamine transmission in schizophrenia. A review and meta-analysis.Q J Nucl Med 1998,42:211–221.PubMedGoogle Scholar
  10. 10.
    Abi-Dargham A, Gil R, Krystal J, et al.:Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort.Am J Psychiatry 1998,155:761–767.PubMedGoogle Scholar
  11. 11.
    Meyer JH, McNeely HE, Sagrati S, et al.:Elevated putamen D(2) receptor binding potential in major depression with motor retardation: an [11C]raclopride positron emission tomography study.Am J Psychiatry 2006,163:1594–1602.PubMedCrossRefGoogle Scholar
  12. 12.
    Parsey RV, Oquendo MA, Zea-Ponce Y, et al.:Dopamine D(2) receptor availability and amphetamine-induced dopamine release in unipolar depression.Biol Psychiatry 2001,50:313–322.PubMedCrossRefGoogle Scholar
  13. 13.
    Of major importance Mayberg HS, Lozano AM, Voon V, et al.:Deep brain stimulation for treatment-resistant depression.Neuron 2005,45:651–660. This is a landmark study that has opened up the field of neurosurgical intervention for affective illness.PubMedCrossRefGoogle Scholar
  14. 14.
    Of major importance Zarate CA, Jr, Singh JB, Carlson PJ, et al.A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression.Arch Gen Psychiatry 2006,63:856–864. The first controlled study of ketamine’s antidepressant actions raises new possibilities for therapy of this stubborn clinical problem.PubMedCrossRefGoogle Scholar
  15. 15.
    Berman RM, Cappiello A, Anand A, et al.:Antidepressant effects of ketamine in depressed patients.Biol Psychiatry 2000,47:351–354.PubMedCrossRefGoogle Scholar
  16. 16.
    Goforth HW, Holsinger T:Rapid relief of severe major depressive disorder by use of preoperative ketamine and electroconvulsive therapy.JECT 2007,23:23–25.Google Scholar
  17. 17.
    Tye KM, Janak PH:Amygdala neurons differentially encode motivation and reinforcement.J Neurosci 2007,27:3937–3945.PubMedCrossRefGoogle Scholar
  18. 18.
    Spezio ML, Huang PY, Castelli F, Adolphs R:Amygdala damage impairs eye contact during conversations with real people.J Neurosci 2007,27:3994–3997.PubMedCrossRefGoogle Scholar
  19. 19.
    Das P, Kemp AH, Flynn G, et al.:Functional disconnections in the direct and indirect amygdala pathways for fear processing in schizophrenia.Schizophr Res 2007,90:284–294.PubMedCrossRefGoogle Scholar
  20. 20.
    Das P, Kemp AH, Liddell BJ, et al.:Pathways for fear perception: modulation of amygdala activity by thalamocortical systems.Neuroimage 2005,26:141–148.PubMedCrossRefGoogle Scholar
  21. 21.
    Tremblay LK, Naranjo CA, Cardenas L, et al.:Probing brain reward system function in major depressive disorder: altered response to dextroamphetamine.Arch Gen Psychiatry 2002,59:409–416.PubMedCrossRefGoogle Scholar
  22. 22.
    Tremblay LK, Naranjo CA, Graham SJ, et al.:Functional neuroanatomical substrates of altered reward processing in major depressive disorder revealed by a dopaminergic probe.Arch Gen Psychiatry 2005,62:1228–1236.PubMedCrossRefGoogle Scholar
  23. 23.
    Winograd-Gurvich C, Fitzgerald PB, Georgiou-Karistianis N, et al.:Negative symptoms: a review of schizophrenia, melancholic depression and Parkinson’s disease.Brain Res Bull 2006,70:312–321.PubMedCrossRefGoogle Scholar
  24. 24.
    Valentin VV, Dickinson A, O’Doherty JP:Determining the neural substrates of goal-directed learning in the human brain.J Neurosci 2007,27:4019–4026.PubMedCrossRefGoogle Scholar
  25. 25.
    Floresco SB, Tse MT:Dopaminergic regulation of inhibitory and excitatory transmission in the basolateral amygdala-prefrontal cortical pathway.J Neurosci 2007,27:2045–2057.PubMedCrossRefGoogle Scholar
  26. 26.
    Grace AA, Rosenkranz JA:Regulation of conditioned responses of basolateral amygdala neurons.Physiol Behav 2002,77:489–493.PubMedCrossRefGoogle Scholar
  27. 27.
    Siegle GJ, Thompson W, Carter CS, et al.:Increased amygdala and decreased dorsolateral prefrontal BOLD responses in unipolar depression: related and independent features.Biol Psychiatry 2007,61:198–209.PubMedCrossRefGoogle Scholar
  28. 28.
    Abi-Dargham A, Rodenhiser J, Printz D, et al.:Increased baseline occupancy of D2 receptors by dopamine in schizophrenia.Proc Natl Acad Sci U S A 2000,97:8104–8109.PubMedCrossRefGoogle Scholar
  29. 29.
    Breier A, Su TP, Saunders R, et al.:Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method.Proc Natl Acad Sci U S A 1997,94:2569–2574.PubMedCrossRefGoogle Scholar
  30. 30.
    Cooper DC:The significance of action potential bursting in the brain reward circuit.Neurochem Int 2002,41:333–340.PubMedCrossRefGoogle Scholar
  31. 31.
    Floresco SB, West AR, Ash B, et al.:Afferent modulation of dopamine neuron firing differentially regulates tonic and phasic dopamine transmission.Nat Neurosci 2003,6:968–973.PubMedCrossRefGoogle Scholar
  32. 32.
    Heien ML, Wightman RM:Phasic dopamine signaling during behavior, reward, and disease states.CNS Neurol Disord Drug Targets 2006,5:99–108.PubMedCrossRefGoogle Scholar
  33. 33.
    Holcomb HH, Lahti AC, Medoff DR, et al.:Sequential regional cerebral blood flow brain scans using PET with H2(15)O demonstrate ketamine actions in CNS dynamically.Neuropsychopharmacology 2001,25:165–172.PubMedCrossRefGoogle Scholar
  34. 34.
    Of major importance Holcomb HH, Lahti AC, Medoff DR, et al.:Effects of noncompetitive NMDA receptor blockade on anterior cingulate cerebral blood flow in volunteers with schizophrenia.Neuropsychopharmacology 2005,30:2275–2282. This is the only study to date that directly compares ketamine-elicited physiologic response in healthy volunteers with schizophrenic subjects using serial positron emission tomography blood flow measurements.PubMedCrossRefGoogle Scholar
  35. 35.
    Of major importance Rowland LM, Bustillo JR, Mullins PG, et al.:Effects of ketamine on anterior cingulate glutamate metabolism in healthy humans: a 4-T proton MRS study.Am J Psychiatry 2005,162:394–396. This is the only study to date that measures glutamatergic response to ketamine in healthy volunteers with high-field MRS.PubMedCrossRefGoogle Scholar
  36. 36.
    Mayberg HS, Brannan SK, Mahurin RK, et al.:Cingulate function in depression: a potential predictor of treatment response.Neuroreport 1997,8:1057–1061.PubMedCrossRefGoogle Scholar
  37. 37.
    Kegeles LS, Abi-Dargham A, Zea-Ponce Y, et al.:Modulation of amphetamine-induced striatal dopamine release by ketamine in humans: implications for schizophrenia.Biol Psychiatry 2000,48:627–640.PubMedCrossRefGoogle Scholar
  38. 38.
    Breier A, Adler CM, Weisenfeld N, et al.:Effects of NMDA antagonism on striatal dopamine release in healthy subjects: application of a novel PET approach.Synapse 1998,29:142–147.PubMedCrossRefGoogle Scholar
  39. 39.
    Lahti AC, Holcomb HH, Medoff DR, Tamminga CA:Ketamine activates psychosis and alters limbic blood flow in schizophrenia.Neuroreport 1995,6:869–872.PubMedCrossRefGoogle Scholar
  40. 40.
    Lahti AC, Weiter MA, Tamara Michaelidis BA, et al.: Effects of ketamine in normal and schizophrenic volunteers.Neuropsychopharmacology 2001,25:455–467.PubMedCrossRefGoogle Scholar
  41. 41.
    Theberge J, Al Semaan Y, Williamson PC, et al.:Glutamate and glutamine in the anterior cingulate and thalamus of medicated patients with chronic schizophrenia and healthy comparison subjects measured with 4.0-T proton MRS.Am J Psychiatry 2003,160:2231–2233.PubMedCrossRefGoogle Scholar
  42. 42.
    Yildiz-Yesiloglu A, Ankerst DP:Review of 1H magnetic resonance spectroscopy findings in major depressive disorder: a meta-analysis.Psychiatry Res 2006,147:1–25.PubMedCrossRefGoogle Scholar
  43. 43.
    Rosenberg DR, Macmaster FP, Mirza Y, et al.:Reduced anterior cingulate glutamate in pediatric major depression: a magnetic resonance spectroscopy study.Biol Psychiatry 2005,58:700–704.PubMedCrossRefGoogle Scholar
  44. 44.
    Auer DP, Putz B, Kraft E, et al.:Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study.Biol Psychiatry 2000,47:305–313.PubMedCrossRefGoogle Scholar
  45. 45.
    Pfleiderer B, Michael N, Erfurth A, et al.:Effective electroconvulsive therapy reverses glutamate/glutamine deficit in the left anterior cingulum of unipolar depressed patients.Psychiatry Res 2003,122:185–192.PubMedCrossRefGoogle Scholar
  46. 46.
    Siegle GJ, Steinhauer SR, Thase ME, et al.:Can’t shake that feeling: event-related fMRI assessment of sustained amygdala activity in response to emotional information in depressed individuals.Biol Psychiatry 2002,51:693–707.PubMedCrossRefGoogle Scholar
  47. 47.
    Takahashi H, Koeda M, Oda K, et al.:An fMRI study of differential neural response to affective pictures in schizophrenia.Neuroimage 2004,22:1247–1254.PubMedCrossRefGoogle Scholar
  48. 48.
    Gur RE, McGrath C, Chan RM, et al.:An fMRI study of facial emotion processing in patients with schizophrenia.Am J Psychiatry 2002,159:1992–1999.PubMedCrossRefGoogle Scholar
  49. 49.
    Hollerman JR, Schultz W:Dopamine neurons report an error in the temporal prediction of reward during learning.Nat Neurosci 1998,1:304–309.PubMedCrossRefGoogle Scholar
  50. 50.
    Schultz W, Tremblay L, Hollerman JR, et al.:Reward prediction in primate basal ganglia and frontal cortex.Neuropharmacology 1998,37:421–429.PubMedCrossRefGoogle Scholar
  51. 51.
    McClure SM, Ericson KM, Laibson DI, et al.:Time discounting for primary rewards.J Neurosci 2007,27:5796–5804.PubMedCrossRefGoogle Scholar
  52. 52.
    Pessiglione M, Seymour B, Flandin G, et al.:Dopaminedependent prediction errors underpin reward-seeking behaviour in humans.Nature 2006,442:1042–1045.PubMedCrossRefGoogle Scholar
  53. 53.
    Of importance Seymour B, O’Doherty JP, Dayan P, et al.:Temporal difference models describe higher-order learning in humans.Nature 2004,429:664–667. This provides an elegant essay on temporal difference models commonly used to study a subject’s response to reward or feedback.PubMedCrossRefGoogle Scholar

Copyright information

© Current Medicine Group LLC 2007

Authors and Affiliations

  1. 1.Department of Psychiatry, Maryland Psychiatry Research CenterUniversity of Maryland School of MedicineBaltimoreUSA

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