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

White matter (WM) abnormalities have implicated schizophrenia (SZ) and bipolar disorder (BD) as disconnection syndromes, yet the extent to which these abnormalities are shared versus distinct remains unclear. Diffusion tensor imaging (DTI) studies yield a putative measure of WM integrity while neuropathological studies provide more specific microstructural information. We therefore systematically reviewed all neuropathological (n = 12) and DTI (n = 11) studies directly comparing patients with SZ and BD. Most studies (18/23) reported no difference between patient groups. Changes in oligodendrocyte density, myelin staining and gene, protein and mRNA expression were found in SZ and/or BD patients as compared to healthy individuals, while DTI studies showed common alterations in thalamic radiations, uncinate fasciculus, corpus callosum, longitudinal fasciculus and corona radiata. Altogether, findings suggest shared disconnectivity in SZ and BD, which are likely related to their considerable overlap. Above all, neuroimaging findings corroborated neuropathological findings in the prefrontal cortex, demonstrating the utility of integrating multiple methodologies. Focusing on clinical dimensions over disease entities will advance our understanding of disconnectivity and help inform preventive medicine.