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 (N-acetylaspartate, NAA) diffusion within axons in patients with BDP (n=21) and healthy controls (n=24). Data were collected from a 1 × 3 × 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.

Figure 1

Representative images depicting the location of our 1 × 3 × 3- white matter voxel in the right prefrontal cortex of a patient.

Figure 2

Sample spectra: one representative subject ¹H spectra acquired from one representative subject. (a) Control without diffusion gradients. (b) Diffusion weighted (diffusion gradients were placed along x and y directions). Cho=Choline; CR=Creatinine; Glx=glutamate and glutamine; NAA=N-acetylaspartate.

Figure 3

Comparison of schizophrenia (SZ) and bipolar disorder (BD) findings based on N-acetylaspartate (NAA) and magnetization transfer ratio (MTR) measures.