Deconstructing psychosis with human brain imaging

Abstract

This review synthesizes our current knowledge on the neurobiology of psychosis from an array of in vivo brain-imaging studies. The evidence base consists of hundreds of studies of patients with schizophrenia and fewer on bipolar disorder but rarely providing direct comparisons between the disorders or integration across methods. Replicated findings in schizophrenia include reduced whole-brain and hippocampal volume as potential vulnerability markers, with further progression at onset; reduced N-acetyl aspartate concentrations in hippocampus and prefrontal cortex; striatal dopamine D(2) receptors upregulation; and alteration in the relation between frontal and temporal activation. These findings are not attributable to medication effects but are of unclear specificity and may apply across the psychosis spectrum. There are consistently replicated associations of psychotic symptoms and cognitive impairment in both structural and functional imaging in schizophrenia but not, as yet, in bipolar disorder. Therefore, it would be premature to dispense with current diagnostic categories because direct comparisons among them are rare, insufficient studies have examined longitudinal changes, and long-term imaging outcome studies in first-episode psychosis have not yet been done. To address these issues and make neuroimaging "clinically relevant," investigators will need to standardize their approaches to data acquisition and analysis, and construct the necessary range of "human brain maps," to implement studies that are sufficiently powered to provide reliable data pertinent to deconstructing psychosis.

Fig. 1.

A Schematic Representation of the Central Role of Neuroimaging Intersecting Between Basic Science and Clinical Applications.

Fig. 2.

Effect sizes of control/patient group difference, calculated separately for neuroleptic-naive (top) and treated patients with Schizophrenia (bottom). The spatial patterns are similar, except that treated patients display generally stronger effect sizes. Blue means that the respective structures were relatively larger in patients than in healthy controls. Thus, treated patients showed a pronounced increase in basal ganglia volumes. (from Davatzikos et al12)

Fig. 3.

Illustration of DTI measures showing fractional anisotropy (a, b) and with delineation of specific ROIs corresponding white matter tracts can be visualized showing front-back (c) and left-right callosal connectivity (d) (courtesy of R. Verma, University of Pennsylvania).

Fig. 4.

An fMRI word-encoding study showing connectivity differences between patients with schizophrenia and healthy controls in left superior temporal gyrus (STG) to dorsolateral prefrontal cortex (DLPFC) and to ventrolateral prefrontal cortex (VLPFC). A region of DLPFC shows greater connectivity with STG in controls, while a region in VLPFC shows greater connectivity with STG in patients (from Wolf et al99).