Schizophrenia, Dopamine and the Striatum: From Biology to Symptoms

Robert A McCutcheon; Anissa Abi-Dargham; Oliver D Howes

doi:10.1016/j.tins.2018.12.004

Schizophrenia, Dopamine and the Striatum: From Biology to Symptoms

Trends Neurosci. 2019 Mar;42(3):205-220. doi: 10.1016/j.tins.2018.12.004. Epub 2019 Jan 6.

Authors

Robert A McCutcheon¹, Anissa Abi-Dargham², Oliver D Howes³

Affiliations

¹ Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, UK; MRC London Institute of Medical Sciences, Hammersmith Hospital, London, W12 0NN, UK; Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, W12 0NN, UK; South London and Maudsley NHS Foundation Trust, London, SE5 8AF, UK.
² Department of Psychiatry, School of Medicine, Stony Brook University, New York, USA.
³ Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, UK; MRC London Institute of Medical Sciences, Hammersmith Hospital, London, W12 0NN, UK; Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, W12 0NN, UK; South London and Maudsley NHS Foundation Trust, London, SE5 8AF, UK. Electronic address: oliver.howes@kcl.ac.uk.

Abstract

The mesolimbic hypothesis has been a central dogma of schizophrenia for decades, positing that aberrant functioning of midbrain dopamine projections to limbic regions causes psychotic symptoms. Recently, however, advances in neuroimaging techniques have led to the unanticipated finding that dopaminergic dysfunction in schizophrenia is greatest within nigrostriatal pathways, implicating the dorsal striatum in the pathophysiology and calling into question the mesolimbic theory. At the same time our knowledge of striatal anatomy and function has progressed, suggesting new mechanisms via which striatal dysfunction may contribute to the symptoms of schizophrenia. This Review draws together these developments, to explore what they mean for our understanding of the pathophysiology, clinical manifestations, and treatment of the disorder.

Keywords: antipsychotic; magnetic resonance imaging; neuroimaging; nigrostriatal; positron emission tomography; psychosis.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Cognition / physiology*
Corpus Striatum / metabolism*
Dopamine / metabolism*
Humans
Neuroimaging* / methods
Psychotic Disorders / metabolism
Schizophrenia / metabolism*

Substances

Dopamine

Abstract

Publication types

MeSH terms

Substances

Grants and funding