Elevated striatal dopamine function linked to prodromal signs of schizophenia

Oliver D. Howes, Andrew J. Montgomery, Marie Claude Asselin, Robin M. Murray, Isabel Valli, Paul Tabraham, Elvira Bramon-Bosch, Lucia Valmaggia, Louise Johns, Matthew Broome, Philip K. McGuire, Paul M. Grasby

    Research output: Contribution to journalArticlepeer-review


    Context: A major limitation on the development of bio- markers and novel interventions for schizophrenia is that its pathogenesis is unknown. Although elevated striatal dopamine activity is thought to be fundamental to schizophrenia, it is unclear when this neurochemical abnormality develops in relation to the onset of illness and how this relates to the symptoms and neurocognitive impairment seen in individuals with prodromal symptoms of schizophrenia. Objectives: To determine whether striatal dopamine function is elevated in individuals with prodromal symptoms of schizophrenia before the onset of psychosis and to assess how this relates to the symptoms and neurocognitive impairment. Design: Case-control study of in vivo striatal dopaminergic function. Setting: Academic research. Patients: Patients were recruited from a community mental health service. Twenty-four patients having prodromal symptoms of schizophrenia were compared with 7 patients having schizophrenia and with 12 matched healthy control subjects from the same community. Main Outcome Measure: Striatal 6-fluoro-L-dopa F 18-dopa uptake measured using positron emission tomographic 18F-dopa imaging. Results: Striatal 18 F-dopa uptake was elevated in patients with prodromal symptoms of schizophrenia (effect size, 0.75) to an intermediate degree compared with that in patients with schizophrenia (effect size, 1.25). The elevation was localized in the associative striatum in both groups. Moreover, striatal 18 F-dopa uptake in patients with prodromal symptoms of schizophrenia was correlated with the severity of prodromal psychopathologic and neuropsychological impairment but not with the severity of anxiety or depressive symptoms. Conclusions: These findings indicate that dopamine over-activity predates the onset of schizophrenia in individuals with prodromal psychotic symptoms, is predominantly localized in the associative striatum, and is correlated with the severity of symptoms and neurocog-nitive dysfunction. © 2009 American Medical Association.
    Original languageEnglish
    Pages (from-to)13-20
    Number of pages7
    JournalArchives of General Psychiatry
    Issue number1
    Publication statusPublished - Jan 2009


    • Adult
    • Brain Mapping
    • physiopathology: Cognition Disorders
    • physiopathology: Corpus Striatum
    • Diagnostic and Statistical Manual of Mental Disorders
    • analogs & derivatives: Dihydroxyphenylalanine
    • physiology: Dominance, Cerebral
    • metabolism: Dopamine
    • Female
    • Humans
    • Image Processing, Computer-Assisted
    • Male
    • Neuropsychological Tests
    • Positron-Emission Tomography
    • Psychiatric Status Rating Scales
    • Reference Values
    • Risk Factors
    • physiopathology: Schizophrenia
    • physiopathology: Schizotypal Personality Disorder
    • Young Adult


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