Department of Economics and Business Economics

Dopamine, psychosis and schizophrenia: the widening gap between basic and clinical neuroscience

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperReviewResearchpeer-review

Documents

DOI

  • J P Kesby, Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Herston, QLD, Australia. j.kesby@uq.edu.au.
  • ,
  • D W Eyles, Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, QLD, 4072, Australia.
  • ,
  • J J McGrath
  • J G Scott, Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Herston, QLD, Australia., Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, QLD, 4072, Australia., The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland 4029, Australia; Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, QLD 4076, Australia; Metro North Mental Health, Royal Brisbane and Women's Hospital, Herston, Queensland 4029, Australia. Electronic address: james.scott@health.qld.gov.au.

The stagnation in drug development for schizophrenia highlights the need for better translation between basic and clinical research. Understanding the neurobiology of schizophrenia presents substantial challenges but a key feature continues to be the involvement of subcortical dopaminergic dysfunction in those with psychotic symptoms. Our contemporary knowledge regarding dopamine dysfunction has clarified where and when dopaminergic alterations may present in schizophrenia. For example, clinical studies have shown patients with schizophrenia show increased presynaptic dopamine function in the associative striatum, rather than the limbic striatum as previously presumed. Furthermore, subjects deemed at high risk of developing schizophrenia show similar presynaptic dopamine abnormalities in the associative striatum. Thus, our view of subcortical dopamine function in schizophrenia continues to evolve as we accommodate this newly acquired information. However, basic research in animal models has been slow to incorporate these clinical findings. For example, psychostimulant-induced locomotion, the commonly utilised phenotype for positive symptoms in rodents, is heavily associated with dopaminergic activation in the limbic striatum. This anatomical misalignment has brought into question how we assess positive symptoms in animal models and represents an opportunity for improved translation between basic and clinical research. The current review focuses on the role of subcortical dopamine dysfunction in psychosis and schizophrenia. We present and discuss alternative phenotypes that may provide a more translational approach to assess the neurobiology of positive symptoms in schizophrenia. Incorporation of recent clinical findings is essential if we are to develop meaningful translational animal models.

Original languageEnglish
Article number30
JournalTranslational Psychiatry
Volume8
Issue1
Pages (from-to)30
Number of pages12
ISSN2158-3188
DOIs
Publication statusPublished - 31 Jan 2018

    Research areas

  • BASAL GANGLIA, D-AMPHETAMINE, DORSOMEDIAL STRIATUM, INCREASED SYNAPTIC DOPAMINE, METHYLAZOXYMETHANOL ACETATE, NUCLEUS-ACCUMBENS-SEPTI, PREFRONTAL CORTEX, PREPULSE INHIBITION, SPATIAL WORKING-MEMORY, ULTRA-HIGH RISK

See relations at Aarhus University Citationformats

Download statistics

No data available

ID: 121284836