Alterations in cortical and extrastriatal subcortical dopamine function in schizophrenia: systematic review and meta-analysis of imaging studies

Joseph Kambeitz , Anissa Abi-Dargham , Shitij Kapur , Oliver D. Howes
  • Declaration of interest

    O.D.H has consulted for and/or spoken at events organised by AstraZeneca, Bristol-Myers Squibb, Janssen, Eli Lilly, Roche and Sunovion. A.A.-D. has consulted or given lectures for Sunovion, Shire, and Bristol-Myers Squibb/Otsuka. S.K. has received grant support from AstraZeneca and GlaxoSmithKline and has served as consultant and/or speaker for AstraZeneca, Bioline, Bristol-Myers Squibb/Otsuka, Eli Lilly, Janssen (Johnson & Johnson), Lundbeck, Neuro-Search, Pfizer, Roche, Servier, and Solvay/Wyeth.

Abstract

Background

The hypothesis that cortical dopaminergic alterations underlie aspects of schizophrenia has been highly influential.

Aims

To bring together and evaluate the imaging evidence for dopaminergic alterations in cortical and other extrastriatal regions in schizophrenia.

Method

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.

Footnotes

  • Funding

    This study was funded by a Medical Research Council (UK) grant to O.D.H. (grant number: MC-A656-5QD30) and the National Institute of Health Research Biomedical Research Council.

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