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Oliver D. Howes, MRCPsych, DM; Andrew J. Montgomery, MRCPsych, PhD; Marie-Claude Asselin, PhD; Robin M. Murray, FRCPsych, DSc; Isabel Valli, MBBS; Paul Tabraham, PhD; Elvira Bramon-Bosch, MRCPsych, PhD; Lucia Valmaggia, PhD; Louise Johns, PhD; Matthew Broome, MRCPsych; Philip K. McGuire, FRCPsych, PhD^*; Paul M. Grasby, MRCPsych, MD^*

Arch Gen Psychiatry. 2009;66(1):13-20.

Context  A major limitation on the development of biomarkers 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 ¹⁸F-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 ¹⁸F-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 overactivity 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 neurocognitive dysfunction.

Author Affiliations: Section of Neuroimaging, Institute of Psychiatry, King's College London (Drs Howes, Murray, Tabraham, Bramon-Bosch, Valmaggia, Johns, Broome, and McGuire and Ms Valli), OASIS (Outreach and Support in South London), South London and Maudsley National Health Service Trust (Drs Howes, Valli, Tabraham, Bramon-Bosch, Valmaggia, Johns, Broome, and McGuire), and Medical Research Council Clinical Sciences Centre (Drs Howes, Montgomery, and Grasby) and Hammersmith Imanet (Dr Asselin), Hammersmith Hospital, London, England. *Drs McGuire and Grasby contributed equally to this article.

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