From the microscope to the magnet: Disconnection in schizophrenia and bipolar disorder

Area of Science:

• Neuroscience
• Psychiatry
• Neuroimaging

Background:

• Schizophrenia (SZ) and bipolar disorder (BD) are increasingly viewed as disconnection syndromes due to white matter (WM) abnormalities.
• The degree to which WM abnormalities are shared or distinct between SZ and BD remains incompletely understood.

Purpose of the Study:

• To systematically review and compare neuropathological and diffusion tensor imaging (DTI) studies investigating WM in SZ and BD.
• To elucidate shared versus distinct WM abnormalities in schizophrenia and bipolar disorder.

Main Methods:

• Systematic review of 12 neuropathological and 11 DTI studies directly comparing patients with SZ and BD.
• Analysis of findings regarding oligodendrocyte density, myelin, gene/protein/mRNA expression, and DTI metrics in specific WM tracts.

Main Results:

• Most comparative studies (18/23) found no significant differences in WM abnormalities between SZ and BD.
• Both neuropathological and DTI studies indicated shared alterations in WM integrity, particularly in the thalamic radiations, uncinate fasciculus, corpus callosum, longitudinal fasciculus, and corona radiata.
• Neuroimaging and neuropathological findings converged, especially in the prefrontal cortex, supporting integrated multi-methodological approaches.

Conclusions:

• Findings suggest significant shared white matter disconnectivity in schizophrenia and bipolar disorder, consistent with their overlapping clinical and genetic features.
• Integrating diverse methodologies, including neuropathology and neuroimaging, enhances understanding of brain disconnectivity in these disorders.
• Future research should focus on clinical dimensions rather than solely disease entities to advance the study of disconnectivity and inform preventive strategies.