title: Alterations in cortical and extrastriatal subcortical dopamine function in schizophrenia: systematic review and meta-analysis of imaging studies.
abstract: BACKGROUND
  The hypothesis that cortical dopaminergic alterations underlie aspects of schizophrenia has been highly influential.
  
  
  OBJECTIVE
  To bring together and evaluate the imaging evidence for dopaminergic alterations in cortical and other extrastriatal regions in schizophrenia.
  
  
  METHODS
  Electronic databases were searched for in vivo molecular studies of extrastriatal dopaminergic function in schizophrenia. Twenty-three studies (278 patients and 265 controls) were identified. Clinicodemographic and imaging variables were extracted and effect sizes determined for the dopaminergic measures. There were sufficient data to permit meta-analyses for the temporal cortex, thalamus and substantia nigra but not for other regions.
  
  
  RESULTS
  The meta-analysis of dopamine D2/D3 receptor availability found summary effect sizes of d = -0.32 (95% CI -0.68 to 0.03) for the thalamus, d = -0.23 (95% CI -0.54 to 0.07) for the temporal cortex and d = 0.04 (95% CI -0.92 to 0.99) for the substantia nigra. Confidence intervals were wide and all included no difference between groups. Evidence for other measures/regions is limited because of the small number of studies and in some instances inconsistent findings, although significant differences were reported for D2/D3 receptors in the cingulate and uncus, for D1 receptors in the prefrontal cortex and for dopamine transporter availability in the thalamus.
  
  
  CONCLUSIONS
  There is a relative paucity of direct evidence for cortical dopaminergic alterations in schizophrenia, and findings are inconclusive. This is surprising given the wide influence of the hypothesis. Large, well-controlled studies in drug-naive patients are warranted to definitively test this hypothesis.
authors.affiliation: Joseph Kambeitz, MD, Department of Psychosis Studies, Institute of Psychiatry, King's College London, UK; Anissa Abi-Dargham, MD, Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, USA;Shitij Kapur, MD, PhD, Department of Psychosis Studies, Institute of Psychiatry, King's College London, UK; Oliver D. Howes, BM, BCh, MA, MRCPsych, PhD, DM, Department of Psychosis Studies, Institute of Psychiatry, King's College London, and Psychiatric Imaging Group, Medical Research Council Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, UK.
authors.forename: Joseph
authors.initials: J
authors.lastname: Kambeitz
authors.affiliation: Joseph Kambeitz, MD, Department of Psychosis Studies, Institute of Psychiatry, King's College London, UK; Anissa Abi-Dargham, MD, Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, USA;Shitij Kapur, MD, PhD, Department of Psychosis Studies, Institute of Psychiatry, King's College London, UK; Oliver D. Howes, BM, BCh, MA, MRCPsych, PhD, DM, Department of Psychosis Studies, Institute of Psychiatry, King's College London, and Psychiatric Imaging Group, Medical Research Council Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, UK.
authors.forename: Anissa
authors.initials: A
authors.lastname: Abi-Dargham
authors.affiliation: Joseph Kambeitz, MD, Department of Psychosis Studies, Institute of Psychiatry, King's College London, UK; Anissa Abi-Dargham, MD, Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, USA;Shitij Kapur, MD, PhD, Department of Psychosis Studies, Institute of Psychiatry, King's College London, UK; Oliver D. Howes, BM, BCh, MA, MRCPsych, PhD, DM, Department of Psychosis Studies, Institute of Psychiatry, King's College London, and Psychiatric Imaging Group, Medical Research Council Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, UK.
authors.forename: Shitij
authors.initials: S
authors.lastname: Kapur
authors.affiliation: Joseph Kambeitz, MD, Department of Psychosis Studies, Institute of Psychiatry, King's College London, UK; Anissa Abi-Dargham, MD, Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, USA;Shitij Kapur, MD, PhD, Department of Psychosis Studies, Institute of Psychiatry, King's College London, UK; Oliver D. Howes, BM, BCh, MA, MRCPsych, PhD, DM, Department of Psychosis Studies, Institute of Psychiatry, King's College London, and Psychiatric Imaging Group, Medical Research Council Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, UK.
authors.forename: Oliver D
authors.initials: OD
authors.lastname: Howes
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000503:physiopathology; D004298:Dopamine / Q000502:physiology*; D006801:Humans; D049268:Positron-Emission Tomography; D012559:Schizophrenia / Q000503:physiopathology*; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000503:physiopathology; D013788:Thalamus / Q000000981:diagnostic imaging / Q000503:physiopathology; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D004298:Dopamine