Reconciling Neuroimaging and Neuropathological Findings in Schizophrenia and Bipolar Disorder

Alex Fornito; Murat Yücel; Christos Pantelis


Curr Opin Psychiatry. 2009;22(3):312-319. 

In This Article

Abstract and Introduction


Purpose of Review: Although structural magnetic resonance imaging (sMRI) and neuropathological investigations offer complementary information that can be used to formulate and test hypotheses about pathophysiological mechanisms in psychiatric disorders, the findings from these two fields are seldom integrated in a systematic manner. In this study, we overview recent sMRI findings in schizophrenia and bipolar disorder and consider how they relate to neuropathological data.
Recent Findings: sMRI research indicates that schizophrenia is associated with volumetric reductions in a network of frontal, temporal, limbic, striatal, and thalamic regions. Some of these abnormalities are apparent prior to psychosis onset and may progress with ongoing illness. sMRI findings in bipolar disorder have been more variable, with both volumetric increases and decreases being reported across several brain regions at different illness stages. Neuropathological studies of both patient groups suggest the cellular changes associated with these volumetric differences affect diverse tissue compartments in a regionally heterogeneous way.
Summary: These findings suggest that any putative pathophysiological mechanism in schizophrenia or bipolar disorder should account for the dynamic, complex, and regionally heterogeneous brain abnormalities seen in these patients. We contend that greater integration of the findings from these two fields will facilitate more targeted and hypothesis-driven research in the future.


Structural magnetic resonance imaging (sMRI) is widely used to investigate brain changes in psychiatric disorders. Numerous reports of regional volumetric differences between healthy controls and various patient groups have been published, although the pathophysiological significance of such changes is a contentious issue[1,2] and causal mechanisms remain unclear. Neuropathological investigations can constrain interpretation of neuroimaging findings by uncovering the putative cellular and molecular changes causing tissue composition differences observed with sMRI. Conversely, neuroimaging data can inform neuropathological work by providing important information regarding regional localization of brain abnormalities and their evolution over the illness course. Despite these complementary strengths, the findings from these two fields are seldom integrated in a systematic manner, hindering the formulation of integrative pathophysiological models.

In this article, we briefly review recent neuroimaging and neuropathological findings in schizophrenia and bipolar disorder and consider their implications for elucidating underlying pathogenic mechanisms. Our discussion of the sMRI literature is focused on understanding what the key brain regions affected by schizophrenia and bipolar disorder are, and what the longitudinal evolution of abnormalities in these areas is across the illness course. We will then consider the histopathological concomitants of these findings, as suggested by post-mortem work.


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