From maps to mechanisms through neuroimaging of schizophrenia

Journal name:
Nature
Volume:
468,
Pages:
194–202
Date published:
DOI:
doi:10.1038/nature09569
Published online

Functional and structural brain imaging has identified neural and neurotransmitter systems involved in schizophrenia and their link to cognitive and behavioural disturbances such as psychosis. Mapping such abnormalities in patients, however, cannot fully capture the strong neurodevelopmental component of schizophrenia that pre-dates manifest illness. A recent strategy to address this issue has been to focus on mechanisms of disease risk. Imaging genetics techniques have made it possible to define neural systems that mediate heritable risk linked to candidate and genome-wide-supported common variants, and mechanisms for environmental risk and gene–environment interactions are emerging. Characterizing the neural risk architecture of schizophrenia provides a translational research strategy for future treatments.

At a glance

Figures

  1. Functional neuroimaging methods and their temporal and spatial resolution.
    Figure 1: Functional neuroimaging methods and their temporal and spatial resolution.

    Magnetoencephalography (MEG) and electroencephalography (EEG) image the electromagnetic effects of neuronal (assembly) action; their temporal resolution can be on the order of milliseconds whereas their spatial resolution tends to be less than that of fMRI, which images blood flow or oxygenation effects of neuronal activation, and PET, which uses radioisotopes to label molecules in the brain. fMRI and PET, in turn, are limited in their temporal resolution to several 100ms (for fMRI) and minutes (for PET).

  2. Brain regions functionally and/or structurally affected in schizophrenia.
    Figure 2: Brain regions functionally and/or structurally affected in schizophrenia.

    Modified, with permission, from ref. 6. PFC, prefrontal cortex.

  3. Schematic summary of putative alterations in dorsolateral prefrontal cortex circuitry in schizophrenia.
    Figure 3: Schematic summary of putative alterations in dorsolateral prefrontal cortex circuitry in schizophrenia.

    Modified, with permission, from ref. 6. Grey, cortical pyramidal neuron; green, parvalbumin-containing interneuron; purple, basket neuron; red, thalamic neuron; yellow, dopaminergic neuron in brainstem.

  4. A systems-level phenotype in patients relates to genetic risk and animal models.
    Figure 4: A systems-level phenotype in patients relates to genetic risk and animal models.

    ac, Abnormal prefrontal–hippocampal connectivity (measured as correlation of activity in PET across task conditions) during working memory (2-back) compared to a control task (0-back) in patients with schizophrenia and matched controls (modified, with permission, from ref. 28) (a), in carriers of the genome-wide significant genetic risk variant (genotype AA) in ZNF804A (modified, with permission, from ref. 76), which again shows persistent coupling between prefrontal cortex and hippocampal formation, this time measured with fMRI during the n-back working memory task (b), and in electrophysiological measurements in a mouse model of high genetic risk (22q11DS) (modified, with permission, from ref. 84) (c). Error bars, standard error.

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  1. Central Institute of Mental Health, University of Heidelberg/Medical Faculty Mannheim, J5, 68159 Mannheim, Germany

    • Andreas Meyer-Lindenberg

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