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Reviews in the Neurosciences

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Volume 24, Issue 4


Does the dopamine hypothesis explain schizophrenia?

Chi-Ieong Lau
  • Department of Neurology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
  • Division of Clinical Neurology, Nuffield Department of Clinical Neurosciences, University of Oxford, UK
  • Other articles by this author:
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/ Han-Cheng Wang
  • Corresponding author
  • Department of Neurology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
  • College of Medicine, National Taiwan University, Taipei, Taiwan
  • College of Medicine, Taipei Medical University, Taipei, Taiwan
  • Email
  • Other articles by this author:
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/ Jung-Lung Hsu
  • Department of Neurology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
  • Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan
  • Graduate Institute of Medical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Mu-En Liu
Published Online: 2013-07-11 | DOI: https://doi.org/10.1515/revneuro-2013-0011


The dopamine hypothesis has been the cornerstone in the research and clinical practice of schizophrenia. With the initial emphasis on the role of excessive dopamine, the hypothesis has evolved to a concept of combining prefrontal hypodopaminergia and striatal hyperdopaminergia, and subsequently to the present aberrant salience hypothesis. This article provides a brief overview of the development and evidence of the dopamine hypothesis. It will argue that the current model of aberrant salience explains psychosis in schizophrenia and provides a plausible linkage between the pharmacological and cognitive aspects of the disease. Despite the privileged role of dopamine hypothesis in psychosis, its pathophysiological rather than etiological basis, its limitations in defining symptoms other than psychosis, as well as the evidence of other neurotransmitters such as glutamate and adenosine, prompt us to a wider perspective of the disease. Finally, dopamine does explain the pathophysiology of schizophrenia, but not necessarily the cause per se. Rather, dopamine acts as the common final pathway of a wide variety of predisposing factors, either environmental, genetic, or both, that lead to the disease. Other neurotransmitters, such as glutamate and adenosine, may also collaborate with dopamine to give rise to the entire picture of schizophrenia.

Keywords: aberrant salience; dopamine; dopamine hypothesis; psychosis; schizophrenia


  • Abbott, C.C., Jaramillo, A., Wilcox, C.E., and Hamilton, D.A. (2013). Antipsychotic drug effects in schizophrenia: a review of longitudinal FMRI investigations and neural interpretations. Curr. Med. Chem. 20, 428–437.PubMedGoogle Scholar

  • Abi-Dargham, A. (2003). Probing cortical dopamine function in schizophrenia: what can D1 receptors tell us? World Psychiatry 2, 166–171.Google Scholar

  • Abi-Dargham, A. and Moore, H. (2003). Prefrontal DA transmission at D1 receptors and the pathology of schizophrenia. Neuroscientist 9, 404–416.Google Scholar

  • Abi-Dargham, A., Gil, R., Krystal, J., Baldwin, R.M., Seibyl, J.P., Bowers, M., van Dyck, C.H., Charney, D.S., Innis, R.B., and Laruelle, M. (1998). Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort. Am. J. Psychiatry 155, 761–767.Google Scholar

  • Abi-Dargham, A., Mawlawi, O., Lombardo, I., Gil, R., Martinez, D., Huang, Y., Hwang, D.R., Keilp, J., Kochan, L., Van Heertum, R., et al. (2002). Prefrontal dopamine D1 receptors and working memory in schizophrenia. J. Neurosci. 22, 3708–3719.Google Scholar

  • Abi-Dargham, A., Xu, X., Thompson, J.L., Gil, R., Kegeles, L.S., Urban, N.B., Narendran, R., Hwang, D., Laruelle, M., and Slifstein, M. (2012). Increased prefrontal cortical D(1) receptors in drug naive patients with schizophrenia: a PET study with [(1)(1)C]NNC112. J. Psychopharmacol. 26, 794–805.Google Scholar

  • Agid, O., Seeman, P., and Kapur, S. (2006). The “delayed onset” of antipsychotic action–an idea whose time has come and gone. J. Psychiatry Neurosci. 31, 93–100.Google Scholar

  • Akil, M., Pierri, J.N., Whitehead, R.E., Edgar, C.L., Mohila, C., Sampson, A.R., and Lewis, D.A. (1999). Lamina-specific alterations in the dopamine innervation of the prefrontal cortex in schizophrenic subjects. Am. J. Psychiatry 156, 1580–1589.Google Scholar

  • Allen, N.C., Bagade, S., McQueen, M.B., Ioannidis, J.P., Kavvoura, F.K., Khoury, M.J., Tanzi, R.E., and Bertram, L. (2008). Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database. Nat. Genet. 40, 827–834.CrossrefPubMedGoogle Scholar

  • Andreasen, N.C. (1982). Negative symptoms in schizophrenia. Definition and reliability. Arch. Gen. Psychiatry 39, 784–788.CrossrefPubMedGoogle Scholar

  • Barch, D.M. and Ceaser, A. (2012). Cognition in schizophrenia: core psychological and neural mechanisms. Trends Cognit. Sci. 16, 27–34.Google Scholar

  • Barch, D.M., Carter, C.S., Braver, T.S., Sabb, F.W., MacDonald, A. 3rd., Noll, D.C., and Cohen, J.D. (2001). Selective deficits in prefrontal cortex function in medication-naive patients with schizophrenia. Arch. Gen. Psychiatry 58, 280–288.CrossrefPubMedGoogle Scholar

  • Berridge, K.C. and Robinson, T.E. (1998). What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? Brain Res. Brain Res. Rev. 28, 309–369.PubMedCrossrefGoogle Scholar

  • Berton, O., McClung, C.A., DiLeone, R.J., Krishnan, V., Renthal, W., Russo, S.J., Graham, D., Tsankova, N.M., Bolanos, C.A., Rios, M., et al. (2006). Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science 311, 864–868.Google Scholar

  • Boison, D., Singer, P., Shen, H.Y., Feldon, J., and Yee, B.K. (2013). Adenosine hypothesis of schizophrenia – opportunities for pharmacotherapy. Neuropharmacology 62, 1527–1543.Google Scholar

  • Boksa, P. and El-Khodor, B.F. (2003). Birth insult interacts with stress at adulthood to alter dopaminergic function in animal models: possible implications for schizophrenia and other disorders. Neurosci. Biobehav. Rev. 27, 91–101.PubMedCrossrefGoogle Scholar

  • Bossong, M.G., van Berckel, B.N., Boellaard, R., Zuurman, L., Schuit, R.C., Windhorst, A.D., van Gerven, J.M., Ramsey, N.F., Lammertsma, A.A., and Kahn, R.S. (2009). Delta 9-tetrahydrocannabinol induces dopamine release in the human striatum. Neuropsychopharmacology 34, 759–766.CrossrefGoogle Scholar

  • Breier, A., Su, T.P., and Pickar, D. (1997). Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. Proc. Natl. Acad. Sci. USA 94, 2569–2574.CrossrefGoogle Scholar

  • Brody, A.L., Olmstead, R.E., London, E.D., Farahi, J., Meyer, J.H., Grossman, P., Lee, G.S., Huang, J., Hahn, E.L., and Mandelkern, M.A. (2004). Smoking-induced ventral striatum dopamine release. Am. J. Psychiatry. 161, 1211–1218.CrossrefGoogle Scholar

  • Butwell, M., Jamieson, E., Leese, M., and Taylor, P. (2000). Trends in special (high-security) hospitals. 2: Residency and discharge episodes, 1986–1995. Br. J. Psychiatry 176, 260–265.Google Scholar

  • Carlsson, A. and Lindqvist, M. (1963). Effect of chlorpromazine or haloperidol on formation of 3methoxytyramine and normetanephrine in mouse brain. Acta Pharmacol. Toxicol. 20, 140–144.Google Scholar

  • Caspi, A., Moffitt, T.E., Cannon, M., McClay, J., Murray, R., Harrington, H., Taylor, A., Arseneault, L., Williams, B., Braithwaite, A., et al. (2005). Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene X environment interaction. Biol. Psychiatry 57, 1117–1127.PubMedCrossrefGoogle Scholar

  • Catafau, A.M., Corripio, I., Pérez, V., Martin, J.C., Schotte, A., Carrió, I., and Alvarez, E. (2006). Dopamine D2 receptor occupancy by risperidone: implications for the timing and magnitude of clinical response. Psychiatry Res. 148, 175–183.CrossrefPubMedGoogle Scholar

  • Coyle, J.T. (2006). Glutamate and schizophrenia: beyond the dopamine hypothesis. Cell. Mol. Neurobiol. 26, 365–384.PubMedGoogle Scholar

  • Crawley, J.C., Owens, D.G., Crow, T.J., Poulter, M., Johnstone, E.C., Smith, T., Oldland, S.R., Veall, N., Owen, F., Zanelli. G.D. (1986). Dopamine D2 receptors in schizophrenia studied in vivo. Lancet 2, 224–225.CrossrefPubMedGoogle Scholar

  • da Silva Alves, F., Figee, M., van Avamelsvoort, T., Veltman, D., and de Haan, L. (2008). The revised dopamine hypothesis of schizophrenia: evidence from pharmacological MRI studies with atypical antipsychotic medication. Psychopharmacol. Bull. 41, 121–132.Google Scholar

  • Davis, K.L., Kahn, R.S., Ko, G., and Davidson, M. (1991). Dopamine in schizophrenia: a review and reconceptualization. Am. J. Psychiatry 148, 1474–1486.Google Scholar

  • Dold, M., Li, C., Tardy, M., Khorsand, V., Gillies, D., and Leucht, S. (2012). Benzodiazepines for schizophrenia. Cochrane Database Syst. Rev. 11, CD006391.Google Scholar

  • Fusar-Poli, P., Howes, O.D., Allen, P., Broome, M., Valli, I., Asselin, M.C., Grasby, P.M., and McGuire, P.K. (2010). Abnormal frontostriatal interactions in people with prodromal signs of psychosis: a multimodal imaging study. Arch. Gen. Psychiatry 67, 683–691.Google Scholar

  • Fusar-Poli, P. and Meyer-Lindenberg, A. (2013). Striatal presynaptic dopamine in schizophrenia, part I: meta-analysis of dopamine active transporter (DAT) density. Schizophr. Bull. 39, 22–32.CrossrefGoogle Scholar

  • Goldman-Rakic, P.S. and Selemon, L.D. (1997). Functional and anatomical aspects of prefrontal pathology in schizophrenia. Schizophr. Bull. 23, 437–458.CrossrefGoogle Scholar

  • Gordon, J.A. (2010). Testing the glutamate hypothesis of schizophrenia. Nat. Neurosci. 13, 2–4.PubMedCrossrefGoogle Scholar

  • Guo, N., Hwang, D.R., Lo, E.S., Huang, Y.Y., Laruelle, M., and Abi-Dargham, A. (2003). Dopamine depletion and in vivo binding of PET D1 receptor radioligands: implications for imaging studies in schizophrenia. Neuropsychopharmacology 28, 1703–1711.CrossrefGoogle Scholar

  • Heinrichs, R.W. (2007). Cognitive improvement in response to antipsychotic drugs: neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial. Arch. Gen. Psychiatry 64, 631–632.PubMedCrossrefGoogle Scholar

  • Honey, G.D., Bullmore, E.T., Soni, W., Varatheesan, M., Williams, S.C.R., and Sharma, T. (1999). Differences in frontal cortical activation by a working memory task after substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia. Proc. Natl. Acad. Sci. USA 96, 13432–13437.CrossrefGoogle Scholar

  • Howes, O.D., Egerton, A., Allan, V., McGuire, P., Stokes, P., and Kapur, S. (2009a). Mechanisms underlying psychosis and antipsychotic treatment response in schizophrenia: insights from PET and SPECT imaging. Curr. Pharm. Des. 15, 2550–2559.CrossrefPubMedGoogle Scholar

  • Howes, O.D., Montgomery, A.J., Asselin, M.C., Murray, R.M., Valli, I., Tabraham, P., Bramon-Bosch, E., Valmaggia, L., Johns, L., Broome, M., et al. (2009b). Elevated striatal dopamine function linked to prodromal signs of schizophrenia. Arch. Gen. Psychiatry 66, 13–20.CrossrefPubMedGoogle Scholar

  • Huttunen, J., Heinimaa, M., Svirskis, T., Nyman, M., Kajander, J., Forsback, S., Solin, O., Ilonen, T., Korkeila, J., Ristkari, T., et al. (2008). Striatal dopamine synthesis in first-degree relatives of patients with schizophrenia. Biol. Psychiatry 63, 114–117.CrossrefPubMedGoogle Scholar

  • Isaac, S.O. and Berridge, C.W. (2003). Wake-promoting actions of dopamine D1 and D2 receptor stimulation. J. Pharmacol. Exp. Ther. 307, 386–394.Google Scholar

  • Jones, H.M., Brammer, M.J., O′Toole, M., Taylor, T., Ohlsen, R.I., Brown, R.G., Purvis, R., Williams, S., and Pilowsky, L.S. (2004). Cortical effects of quetiapine in first-episode schizophrenia: a preliminary functional magnetic resonance imaging study. Biol. Psychiatry 56, 938–942.CrossrefGoogle Scholar

  • Kahn, R.S., Harvey, P.D., Davidson, M., Keefe, R.S., Apter, S., Neale, J.M., Mohs, R.C., and Davis, K.L. (1994). Neuropsychological correlates of central monoamine function in chronic schizophrenia: relationship between CSF metabolites and cognitive function. Schizophr. Res. 11, 217–224.PubMedCrossrefGoogle Scholar

  • Kapur, S. (2003). Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. Am. J. Psychiatry 160, 13–23.Google Scholar

  • Kapur, S., Zipursky, R.B., and Remington, G. (1999). Clinical and theoretical implications of 5-HT2 and D2 receptor occupancy of clozapine, risperidone, and olanzapine in schizophrenia. Am. J. Psychiatry 156, 286–293.Google Scholar

  • Karlsson, P., Farde, L., Halldin, C., and Sedvall, G. (2002). PET study of D(1) dopamine receptor binding in neuroleptic-naive patients with schizophrenia. Am. J. Psychiatry 159, 761–767.Google Scholar

  • Kebabian, J.W. and Calne, D.B. (1979). Multiple receptors for dopamine. Nature 277, 93–96.Google Scholar

  • Kestler, L.P., Walker, E., and Vega, E.M. (2001). Dopamine receptors in the brains of schizophrenia patients: a meta-analysis of the findings. Behav. Pharmacol. 12, 355–371.PubMedCrossrefGoogle Scholar

  • King, M.V., Seeman, P., Marsden, C.A., and Fone, K.C. (2009). Increased dopamine D2High receptors in rats reared in social isolation. Synapse 63, 476–483.CrossrefPubMedGoogle Scholar

  • Kirsch, P., Ronshausen, S., Mier, D., and Gallhofer, B. (2007). The influence of antipsychotic treatment on brain reward system reactivity in schizophrenia patients. Pharmacopsychiatry 40, 196–198.CrossrefPubMedGoogle Scholar

  • Knable, M.B., Hyde, T.M., Herman, M.M, Carter, J.M, Bigelow, L., and Kleinman, J.E. (1994). Quantitative autoradiography of dopamine-D1 receptors, D2 receptors, and dopamine uptake sites in postmortem striatal specimens from schizophrenic patients. Biol. Psychiatry 36, 827–835.PubMedCrossrefGoogle Scholar

  • Knable, M.B., Hyde, T.M., Murray, A.M., Herman, M.M., and Kleinman, J.E. (1996). A postmortem study of frontal cortical dopamine D1 receptors in schizophrenics, psychiatric controls, and normal controls. Biol. Psychiatry 40, 1191–1199.PubMedCrossrefGoogle Scholar

  • Kosaka, J., Takahashi, H., Ito, H., Takano, A., Fujimura, Y., Matsumoto, R., Nozaki, S., Yasuno, F., Okubo, Y., Kishimoto, T., et al. (2010). Decreased binding of [11C]NNC112 and [11C]SCH23390 in patients with chronic schizophrenia. Life Sci. 86, 814–818.Google Scholar

  • Kraguljac, N.V., Reid, M., White, D., Jones, R., den Hollander, J., Lowman, D., and Lahti, A.C. (2012). Neurometabolites in schizophrenia and bipolar disorder – a systematic review and meta-analysis. Psychiatry Res. 203, 111–125.CrossrefGoogle Scholar

  • Laruelle, M. (2000). The role of endogenous sensitization in the pathophysiology of schizophrenia: implications from recent brain imaging studies. Brain Res. Brain Res. Rev. 31, 371–384.CrossrefPubMedGoogle Scholar

  • Laruelle, M., Abi-Dargham, A., Gil, R., Kegeles, L., and Innis, R. (1999). Increased dopamine transmission in schizophrenia: relationship to illness phases. Biol. Psychiatry 46, 56–72.Google Scholar

  • Laruelle, M., Abi-Dargham, A., van Dyck, C.H., Gil, R., D’Souza, C.D., Erdos, J., McCance, E., Rosenblatt, W., Fingado, C., Zoghbi, S.S., et al. (1996). Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proc. Natl. Acad. Sci. USA 93, 9235–9240.CrossrefGoogle Scholar

  • Leucht, S., Busch, R., Hamann, J., Kissling, W., and Kane, J.M. (2005). Early-onset hypothesis of antipsychotic drug action: a hypothesis tested, confirmed and extended. Biol. Psychiatry 57, 1543–1549.CrossrefGoogle Scholar

  • Lewis, R., Kapur, S., Jones, C., DaSilva, J., Brown, G.M., Wilson, A.A., Houle, S., and Zipursky, R.B. (1999). Serotonin 5-HT2 receptors in schizophrenia: a PET study using [18F]setoperone in neuroleptic-naive patients and normal subjects. Am. J. Psychiatry 156, 72–78.Google Scholar

  • Lund, A., Kroken, R., Thomsen, T., Hugdahl, K., Smievoll, A.I., Barndon, R., Iversen, J., Landrø, N.I., Sundet, K., Rund, B.R., et al. (2002). “Normalization” of brain activation in schizophrenia. An fMRI study. Schizophr. Res. 58, 333–335.CrossrefPubMedGoogle Scholar

  • Martinot, J.L., Paillere-Martinot, M.L., Loc′h, C., Hardy, P., Poirier, M.F., Mazoyer, B., Beaufils, B., Mazière, B., Allilaire, J.F., and Syrota, A. (1991). The estimated density of D2 striatal receptors in schizophrenia. A study with positron emission tomography and 76Br-bromolisuride. Br. J. Psychiatry 158, 346–350.Google Scholar

  • Martinot, J.L., Paillere-Martinot, M.L., Loc′h, C., Lecrubier, Y., Dao-Castellana, M.H., Aubin, F., Allilaire, J.F., Mazoyer, B., Mazière, B., and Syrota, A. (1994). Central D2 receptors and negative symptoms of schizophrenia. Br. J. Psychiatry 164, 27–34.Google Scholar

  • McClelland, G.R., Cooper, S.M., and Pilgrim, A.J. (1990). A comparison of the central nervous system effects of haloperidol, chlorpromazine and sulpiride in normal volunteers. Br. J. Clin. Pharmacol. 30, 795–803.Google Scholar

  • McGowan, S., Lawrence, A.D., Sales, T., Quested, D., and Grasby, P. (2004). Presynaptic dopaminergic dysfunction in schizophrenia: a positron emission tomographic [18F]fluorodopa study. Arch. Gen. Psychiatry 61, 134–142.CrossrefGoogle Scholar

  • Meisenzahl, E.M., Scheuerecker, J., Zipse, M., Ufer, S., Wiesmann, M., Frodl, T., Koutsouleris, N., Zetzsche, T., Schmitt, G., Riedel, M., et al (2006). Effects of treatment with the atypical neuroleptic quetiapine on working memory function: a functional MRI follow-up investigation. Eur. Arch. Psychiatry Clin. Neurosci. 256, 522–531.CrossrefGoogle Scholar

  • Meltzer, H.Y. (1979). Clinical evidence for multiple dopamine receptors in man. Commun. Psychopharmacol. 3, 457–470.PubMedGoogle Scholar

  • Meltzer, H.Y. (1989). Clinical studies on the mechanism of action of clozapine: the dopamine-serotonin hypothesis of schizophrenia. Psychopharmacology 99 Suppl, S18–S27.PubMedGoogle Scholar

  • Meltzer, H.Y., Sommers, A.A., and Luchins, D.J. (1986). The effect of neuroleptics and other psychotropic drugs on negative symptoms in schizophrenia. J. Clin. Psychopharmacol. 6, 329–338.Google Scholar

  • Meyer, U. and Feldon, J. (2009). Prenatal exposure to infection: a primary mechanism for abnormal dopaminergic development in schizophrenia. Psychopharmacology 206, 587–602.Google Scholar

  • Monchi, O., Taylor, J.G., and Dagher, A. (2000). A neural model of working memory processes in normal subjects, Parkinson’s disease and schizophrenia for fMRI design and predictions. Neural Networks 13, 953–973.CrossrefGoogle Scholar

  • Moncrieff, J. (2009). A critique of the dopamine hypothesis of schizophrenia and psychosis. Harv. Rev. Psychiatry 17, 214–225.PubMedCrossrefGoogle Scholar

  • Nieratschker, V., Nothen, M.M., and Rietschel, M. (2010). New genetic findings in schizophrenia: Is there still room for the dopamine hypothesis of schizophrenia? Front Behav. Neurosci. 4, 1–10. doi: 10.3389/fnbeh.2010.00023.CrossrefGoogle Scholar

  • Nikolaus, S., Antke, C., and Müller, H.W. (2009). In vivo imaging of synaptic function in the central nervous system: II. Mental and affective disorders. Behav. Brain Res. 204, 32–66.CrossrefPubMedGoogle Scholar

  • Ogawa, S. and Lee, T.M. (1990). Magnetic resonance imaging of blood vessels at high fields: in vivo and in vitro measurements and image simulation. Magn. Reson. Med. 16, 9–18.CrossrefPubMedGoogle Scholar

  • Okubo, Y., Suhara, T., Suzuki, K., Kobayashi, K., Inoue, O., Terasaki, O., Someya, Y., Sassa, T., Sudo, Y., Matsushima, E., et al. (1997). Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET. Nature 385, 634–636.Google Scholar

  • Patil, S. T., Zhang, L., Martenyi, F., Lowe, S.L., Jackson, K.A., Andreev, B.V, Avedisova, A.S, Bardenstein, L.M, Gurovich, I.Y., Morozova, M.A., et al. (2007). Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial. Nat. Med. 13, 1102–1107.CrossrefGoogle Scholar

  • Pearce, R.K., Seeman, P., Jellinger, K., and Tourtellotte, W.W. (1990). Dopamine uptake sites and dopamine receptors in Parkinson’s disease and schizophrenia. Eur. Neurol. 30 Suppl 1, 9–14.Google Scholar

  • Pearlson, G.D., Tune, L.E., Wong, D.F., Aylward, E.H., Barta, P.E., Powers, R.E., Tien, A.Y., Chase, G.A., Harris, G.J., Rabins, P.V. (1993). Quantitative D2 dopamine receptor PET and structural MRI changes in late-onset schizophrenia. Schizophr. Bull. 19, 783–795.CrossrefPubMedGoogle Scholar

  • Pilowsky, L.S., Bressan, R.A., Stone, J.M., Erlandsson, K., Mulligan, R.S., Krystal, J.H., and Ell, P.J. (2006). First in vivo evidence of an NMDA receptor deficit in medication-free schizophrenic patients. Mol. Psychiatry 11, 118–119.CrossrefPubMedGoogle Scholar

  • Pilowsky, L.S., Costa, D.C., Ell, P.J., Murray, R.M., Verhoeff, N.P., and Kerwin, R.W. (1992). Clozapine, single photon emission tomography, and the D2 dopamine receptor blockade hypothesis of schizophrenia. Lancet 340, 199–202.Google Scholar

  • Pilowsky, L.S., Costa, D.C., Ell, P.J., Murray, R.M., Verhoeff, N.P., and Kerwin, R.W. (1993). Antipsychotic medication, D2 dopamine receptor blockade and clinical response: a 123I IBZM SPET (single photon emission tomography) study. Psychol. Med. 23, 791–797.Google Scholar

  • Port, J.D. and Agarwal, N. (2011). MR spectroscopy in schizophrenia. J. Magn. Reson. Imaging 34, 1251–1261.Google Scholar

  • Pruessner, J.C., Champagne, F., Meaney, M.J., and Dagher, A. (2004). Dopamine release in response to a psychological stress in humans and its relationship to early life maternal care: a positron emission tomography study using [11C]raclopride. J. Neurosci. 24, 2825–2831.CrossrefGoogle Scholar

  • Remington, G. and Kapur, S. (1999). D2 and 5-HT2 receptor effects of antipsychotics: bridging basic and clinical findings using PET. J. Clin. Psychiatry 60 (Suppl 10), 15–19.Google Scholar

  • Roiser, J.P., Stephan, K.E., and Joyce, E.M. (2009). Do patients with schizophrenia exhibit aberrant salience? Psychol. Med. 39, 199–209.CrossrefPubMedGoogle Scholar

  • Rothman, R.B., Baumann, M.H., Dersch, C.M., Romero, D.V., Rice, K.C., Carroll, F.I., and Partilla, J.S. (2001). Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse 39, 32–41.PubMedCrossrefGoogle Scholar

  • Rowland, L.M., Kontson, K., West, J., Edden, R.A., Zhu, H., Wijtenburg, S.A., Holcomb, H.H., and Barker, P.B. (2012). In vivo measurements of glutamate, GABA, and NAAG in schizophrenia. Schizophr. Bull. Oct 18. [Epub ahead of print].Google Scholar

  • Rzanny, R., Klemm, S., Reichenbach, J.R., Pfleiderer, S.O., Schmidt, B., Volz, H.P., Blanz, B., and Kaiser, W.A. (2003). 31P-MR spectroscopy in children and adolescents with a familial risk of schizophrenia. Eur. Radiol. 13, 763–770.Google Scholar

  • Seeman, P. and Lee, T. (1975). Antipsychotic drugs: direct correlation between clinical potency and presynaptic action on dopamine neurons. Science 188, 1217–1219.Google Scholar

  • Snitz, B.E., MacDonald, A. 3rd, Cohen, J.D., Cho, R.Y., Becker, T., and Carter, C.S. (2005). Lateral and medial hypofrontality in first-episode schizophrenia: functional activity in a medication-naive state and effects of short-term atypical antipsychotic treatment. Am. J. Psychiatry 162, 2322–2329.Google Scholar

  • Stanley, J.A., Williamson, P.C., Drost, D.J., Carr, T.J., Rylett, R.J., Morrison-Stewart, S., and Thompson, R.T. (1994). Membrane phospholipid metabolism and schizophrenia. An in vivo 31P-MR spectroscopy study. Schizophr. Res. 13, 209–215.Google Scholar

  • Stefanis, N.C., Henquet, C., Avramopoulos, D., Smyrnis, N., Evdokimidis, I., Myin-Germeys, I., Stefanis, C.N., and Van Os, J. (2007). COMT Val158Met moderation of stress-induced psychosis. Psychol. Med. 37, 1651–1656.Google Scholar

  • Taylor, D.M. and Duncan-McConnell, D. (2000). Refractory schizophrenia and atypical antipsychotics. J. Psychopharmacol. 14, 409–418.Google Scholar

  • Taylor, K.I., Zach, P., and Brugger, P. (2002). Why is magical ideation related to leftward deviation on an implicit line bisection task? Cortex 38, 247–252.PubMedCrossrefGoogle Scholar

  • Taylor, S.F., Koeppe, R.A., Tandon, R., Zubieta, J.K., and Frey, K.A. (2000). In vivo measurement of the vesicular monoamine transporter in schizophrenia. Neuropsychopharmacology 23, 667–675.PubMedCrossrefGoogle Scholar

  • Thomas, M.A., Ke, Y., Levitt, J., Caplan, R., Curran, J., Asarnow, R., and McCracken, J. (1998). Preliminary study of frontal lobe 1H MR spectroscopy in childhood-onset schizophrenia. J. Magn. Reson. Imaging 8, 841–846.Google Scholar

  • Tune, L., Barta, P., Wong, D., Powers, R.E., Pearlson, G., Tien, A.Y., and Wagner, H.N. (1996). Striatal dopamine D2 receptor quantification and superior temporal gyrus: volume determination in 14 chronic schizophrenic subjects. Psychiatry Res. 67, 155–158.CrossrefPubMedGoogle Scholar

  • Ujike, H. (2002). Stimulant-induced psychosis and schizophrenia: the role of sensitization. Curr. Psychiatry Rep. 4, 177–184.CrossrefPubMedGoogle Scholar

  • van Os, J. (2009). A salience dysregulation syndrome. Br. J. Psychiatry 194, 101–103.Google Scholar

  • van Os, J., Rutten, B.P., and Poulton, R. (2008). Gene-environment interactions in schizophrenia: review of epidemiological findings and future directions. Schizophr. Bull. 34, 1066–1082.CrossrefPubMedGoogle Scholar

  • Vollenweider, F.X., Vontobel, P., Oye, I., Hell, D., and Leenders, K.L. (2000). Effects of (S)-ketamine on striatal dopamine: a [11C]raclopride PET study of a model psychosis in humans. J. Psychiatr. Res. 34, 35–43.Google Scholar

  • Waddington, J.L., O’Callaghan, E., Buckley, P., Larkin, C., Redmond, O., Stack, J., and Ennis, J.T. (1992). MR imaging and spectroscopy in schizophrenia in relation to the neurodevelopmental hypothesis. Clin. Neuropharmacol. 15 Suppl 1 Pt A, 118A–119A.CrossrefGoogle Scholar

  • Walsh, E., Leese, M., Taylor, P., Johnston, I., Burns, T., Creed, F., Higgit, A., and Murray, R. (2002). Psychosis in high-security and general psychiatric services: report from the UK700 and special hospitals’ treatment resistant schizophrenia groups. Br. J. Psychiatry 180, 351–357.Google Scholar

  • Walter, H., Heckers, S., Kassubek, J., Erk, S., Frasch, K., and Abler, B. (2010). Further evidence for aberrant prefrontal salience coding in schizophrenia. Front. Behav. Neurosci. 3, 1–9. doi: 10.3389/neuro.08.062.2009.CrossrefGoogle Scholar

  • Walter, H., Kammerer, H., Frasch, K., Spitzer, M., and Abler, B. (2009). Altered reward functions in patients on atypical antipsychotic medication in line with the revised dopamine hypothesis of schizophrenia. Psychopharmacology 206, 121–132.Google Scholar

  • Weiss, E.M., Siedentopf, C., Golaszewski, S., Mottaghy, F.M., Hofer, A., Kremser, C., Felber, S., and Fleischhacker, W.W. (2007). Brain activation patterns during a selective attention test–a functional MRI study in healthy volunteers and unmedicated patients during an acute episode of schizophrenia. Psychiatry Res. 154, 31–40.CrossrefGoogle Scholar

  • Wise, R.A., Spindler, J., deWit, H., and Gerberg, G.J. (1978). Neuroleptic-induced “anhedonia” in rats: pimozide blocks reward quality of food. Science 201, 262–264.Google Scholar

  • Wolf, R.C., Vasic, N., Höse, A., Spitzer, M., and Walter, H.. (2007). Changes over time in frontotemporal activation during a working memory task in patients with schizophrenia. Schizophr. Res. 91, 141–150.CrossrefPubMedGoogle Scholar

  • Wong, D.F., Wagner, H.N. Jr., Tune, L.E., Dannals, R.F., Pearlson, G.D., Links, J.M., Tamminga, C.A., Broussolle, E.P., Ravert, H.T., Wilson, A.A, et al. (1986). Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics. Science 234, 1558–1563.Google Scholar

  • Yamasue, H., Fukui, T., Fukuda, R., Yamada, H., Yamasaki, S., Kuroki, N., Abe, O., Kasai, K., Tsujii, K., Iwanami, A., et al. (2002). 1H-MR spectroscopy and gray matter volume of the anterior cingulate cortex in schizophrenia. Neuroreport 13, 2133–2137.PubMedCrossrefGoogle Scholar

  • Zakzanis, K.K. and Hansen, K.T. (1998). Dopamine D2 densities and the schizophrenic brain. Schizophr. Res. 32, 201–206.PubMedCrossrefGoogle Scholar

About the article

Chi-Ieong Lau

Chi-Ieong David Lau is a Consultant Neurologist whose research interests focus on the cognitive neuroscience underpinning neurological diseases. His recent work includes the investigation of the visual system in migraine, as well as the modulation of slow-wave-sleep-related memory consolidation using a variety of methods, including EEG, neuroimaging, brain stimulation, and genetics. He completed his medical degree and neurology training in Taiwan and postgraduate studies at the University College London and the University of Oxford, supported by the British Chevening Scholarship.

Han-Cheng Wang

Han-Cheng Wang is a Consultant Neurologist at Shin Kong Wu Ho-Su Memorial Hospital, with specialist clinics for Parkinson’s disease and movement disorders. He is Assistant Professor of Neurology at the College of Medicine, National Taiwan University. He is the former President and present Standing Member of the Executive Board of Taiwan Movement Disorder Society. His research interests include understanding basic neurophysiology underlying human movements and movement disorders. He is interested in linking clinical features with functional connectivity of the brain, reflected in his recent works correlating regional cerebral blood flow (CBF) changes and tract-specific abnormalities with severity of Parkinsonism.

Jung-Lung Hsu

Jung-Lung Hsu is a Clinical Neurologist. He is interested in behavioral/cognitive neuroscience. His main study is focused on brain structural change and human behavior. He is also participating in the event-related potential (ERP) study (P50 and MMN) of schizophrenia patients.

Mu-En Liu

Mu-En Liu’s research interests include biological psychiatry and geriatric psychiatry. Some of the study topics are novel in the genetic study of cognitive ageing. Recently, he examined genetic effects on age-related morphologic changes in the brain. His researches may clarify the underlying molecular mechanisms of brain aging.

Corresponding author: Han-Cheng Wang, Department of Neurology, Shin Kong Wu Ho-Su Memorial Hospital, 95 Wen-Chang Road, Shih-Lin District, Taipei, Taiwan; College of Medicine, National Taiwan University, Taipei, Taiwan; and College of Medicine, Taipei Medical University, Taipei, Taiwan

Received: 2013-04-17

Accepted: 2013-06-05

Published Online: 2013-07-11

Published in Print: 2013-08-01

Citation Information: Reviews in the Neurosciences, Volume 24, Issue 4, Pages 389–400, ISSN (Online) 2191-0200, ISSN (Print) 0334-1763, DOI: https://doi.org/10.1515/revneuro-2013-0011.

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