Myelin vs Axon Abnormalities in White Matter in Bipolar Disorder

Abstract

White matter (WM) abnormalities are among the most commonly reported neuroimaging findings in bipolar disorder. Nonetheless, the specific nature and pathophysiology of these abnormalities remain unclear. Use of a combination of magnetization transfer ratio (MTR) and diffusion tensor spectroscopy (DTS) permits examination of myelin and axon abnormalities separately. We aimed to examine myelination and axon geometry in euthymic patients with bipolar disorder with psychosis (BDP) by combining these two complementary noninvasive MRI techniques. We applied a combined MRI approach using MTR to study myelin content and DTS to study metabolite (Nacetylaspartate, NAA) diffusion within axons in patients with BDP (n ¼ 21) and healthy controls (n ¼ 24). Data were collected from a 1 Â 3 Â 3-cm voxel within the right prefrontal cortex WM at 4 Tesla. Clinical and cognitive data were examined in association with MTR and DTS data. MTR was significantly reduced in BDP, suggesting reduced myelin content. The apparent diffusion coefficient of NAA did not differ from healthy controls, suggesting no changes in axon geometry in patients with BDP. These findings suggest that patients with BDP exhibit reduced myelin content, but no changes in axon geometry compared with controls. These findings are in contrast with our recent findings, using the same techniques, in patients with schizophrenia (SZ), which suggest both myelination and axon abnormalities in SZ. This difference may indicate that alterations in WM in BDP may have unique causes and may be less extensive than WM abnormalities seen in SZ.

Brain network analysis reveals affected connectome structure in bipolar I disorder

“…The observed reductions in interhemispheric connectivity in bipolar I disorder patients are consistent with previous reports of reduced integrity of the CC in bipolar disorder [Barysheva et al, ; Emsell et al, ; Lagopoulos et al, ; Leow et al, ; Sarrazin et al, ; Torgerson et al, ; Wang et al, ] and may be reflective of a decrease in the number, density, caliber, and/or myelination of callosal axons, with recent findings pointing more towards myelination than axon abnormalities [Lewandowski et al, ]. Around 200–250 million axons pass through the CC [Nishikimi et al, ; Paul et al, ] to connect primary, secondary, and higher‐order cortices [Aboitiz et al, ].…”

Association of intracortical myelin and cognitive function in bipolar I disorder

“…Indeed, many prior histological studies in BD show fewer overall oligodendrocytes, decreased number of oligodendrocytes per neuron, and reduced expression of myelin‐related genes in the prefrontal cortex in individuals with BD . Together, these studies suggest that myelin‐related pathology may extend into the cerebral cortex in BD.…”

Connectome Disconnectivity and Cortical Gene Expression in Patients With Schizophrenia

“…These findings argue for potentially converging pathophysiologic mechanisms in the two disorders (60). Indeed, the diffusionweighted MRI metric of FA is often interpreted as a proxy of white matter microstructure-rather than a metric of tract volume (35)-and studies have suggested white matter abnormalities in bipolar disorder to be concentrated around a reduction in myelin content rather than abnormalities in axonal geometry or tract volume (61,62). This is in contrast to SCZ, where both myelination deficits and axon abnormalities have been reported (63).…”