Reduced myelination of white matter in patients with affective disorders according to fast macromolecular proton fraction mapping

Abstract. This study aimed to test the method of fast molecular proton fraction mapping as a tool for quantitative assessment of myelin deficiency in affective disorders between general and local measurements in seven selected regions of interest of both hemispheres in comparison with the control group, determining the sensitivity and specificity of the method.

Materials and methods. The study included 24 patients with affective disorders, 13 were diagnosed with a current depressive episode as part of recurrent depressive disorder, and 11 were diagnosed with bipolar affective disorder. All patients underwent non-contrast magnetic resonance imaging of the brain using a fast MPF mapping protocol. Comparison of the MPF levels for the control and experimental groups were calculated using the Mann-Whitney U-test. ROC analysis was used to assess the prognostic value of the investigating parameters.

Results. The average MPF indices of all selected regions of interest for the control group and group of patients with affective disorders (AD) were significantly different (p < 0.0001). In a pairwise comparison of each selected area, patients with AD showed a significant decrease in MPF in all selected areas of white matter compared to the control group (p < 0.05). Analyzing the ROC curves, the largest areas under the ROC curves (AUC) were 0.892 ± 0.061 (83.3%; 88.89%) and 0.888 ± 0.054 (70.83%; 83.3%) in the periventricular zone and thalamic area respectively. which indicates the “high” information content of these models for detecting the process of hypomyelination in patients with AR.

Conclusion. Affective disorders are characterized by a significant decrease in the MPF of the white matter of the brain in comparison with the control group (p < 0.05), which indicates a decrease in the concentration of myelin in the observed areas. The process of hypomyelination is diffuse as it was significantly expressed in all selected regions of interest in patients with affective disorders, including the periventricular zone and the area of thalamus and basal ganglia in comparison with controls (p < 0.05). MPF changes in the periventricular zone have the greatest diagnostic value for detecting hypomyelination in AD (PPV = 91%, NPV = 80%).

1. Malhi G.S., Das P., Outhred T. et al. Default mode dysfunction underpins suicidal activity in mood disorders. Psychol. Med. 2020; 50: 1214–1223. https://doi.org/10.1017/S0033291719001132

2. Wu G., Mei B., Hou X. et al. White matter microstructure changes in adults with major depressive disorder: evidence from diffusion magnetic resonance imaging. BJPsych Open. 2023; 9 (3): e101. https://doi.org/10.1192/bjo.2023.30

3. Linke J.O., Adleman N.E., Sarlls J. et al. White Matter Microstructure in Pediatric Bipolar Disorder and Disruptive Mood Dysregulation Disorder. J. Am. Acad. Child Adolesc. Psychiatry. 2020; 59 (10): 1135–1145. https://doi.org/10.1016/j.jaac.2019.05.035

4. Winklewski P.J., Sabisz A., Naumczyk P. et al. Understanding the Physiopathology Behind Axial and Radial Diffusivity Changes – What Do We Know? Front. Neurol. 2018; 9. https://doi.org/10.3389/fneur.2018.00092

5. Kisel A.A., Naumova A.V., Yarnykh V.L. Macromolecular Proton Fraction as a Myelin Biomarker: Principles, Validation, and Applications. Front. Neurosci. 2022; 16: 819–912. https://doi.org/10.3389/fnins.2022.819912

6. Smirnova L.P., Yarnykh V.L., Parshukova D.A. et al. Global hypomyelination of the brain white and gray matter in schizophrenia: quantitative imaging using macromolecular proton fraction. Transl. Psychiatr. 2021; 11 (1): 365. https://doi.org/10.1038/s41398-021-01475-8

7. Kamaeva D.A., Smirnova L.P., Vasilieva S.N. et al. Catalytic Antibodies in Bipolar Disorder: Serum IgGs Hydrolyze Myelin Basic Protein. Int. J. Mol. Sci. 2022; 23 (13): 7397. https://doi.org/10.3390/ijms23137397

8. Rantala M.J., Luoto S., Borráz-León J.I., Krams I. Bipolar disorder: An evolutionary psychoneuroimmunological approach. Neurosci. Biobehav. Rev. 2021; 122: 28–37. https://doi.org/10.1016/j.neubiorev.2020.12.031

9. Valdés-Tovar M., Rodríguez-Ramírez A.M., Rodríguez-Cárdenas L. et al. Insights into myelin dysfunction in schizophrenia and bipolar disorder. Wld J. Psychiatr. 2022; 12 (2): 264–285. https://doi.org/10.5498/wjp.v12.i2.264

10. Fries G.R., Saldana V.A., Finnstein J., Rein T. Molecular pathways of major depressive disorder converge on the synapse. Mol. Psychiatr. 2023; 28 (1): 284–297. https://doi.org/10.1038/s41380-022-01806-1

11. Kieseppä T., Mäntylä R., Luoma K. et al. White Matter Hyperintensities after Five-Year Follow-Up and a Cross-Sectional FA Decrease in Bipolar I and Major Depressive Patients. Neuropsychobiology. 2022; 81 (1): 39–50. https://doi.org/ 10.1159/000516234

12. Oudega M.L., Siddiqui A., Wattjes M.P. et al. Are Apathy and Depressive Symptoms Related to Vascular White Matter Hyperintensities in Severe Late Life Depression? J. Geriatr. Psychiatr. Neurol. 2021; 34 (1): 21–28. https://doi.org/10.1177/0891988720901783

13. Saccaro L.F., Schilliger Z., Dayer A. et al. Inflammation, anxiety, and stress in bipolar disorder and borderline personality disorder: A narrative review. Neurosci. Biobehav. Rev. 2021; 127: 184–192. https://doi.org/10.1016/j.neubiorev.2021.04.017

14. Yusupova E.F., Gaynetdinova DD. Periventricular leucomalacia: etiology, pathogenesis, clinical signs, outcomes. Voprosy sovremennoj pediatrii= Issues of modern pediatrics. 2010; 9 (4): 68–72. (In Russian)

15. Brown J.A., Jackson B.S., Burton C.R. et al. Reduced white matter microstructure in bipolar disorder with and without psychosis. Bipolar Disord. 2021; 23 (8): 801–809. https://doi.org/10.1111/bdi.13055

16. Zhou L., Wang L., Wang M. et al. Alterations in white matter microarchitecture in adolescents and young adults with major depressive disorder: A voxel-based meta-analysis of diffusion tensor imaging. Psychiatr. Res. Neuroimaging. 2022; 323: 111482. https://doi.org/10.1016/j.pscychresns.2022.111482

17. Zhang Y., Roy D.S., Zhu Y. et al. Targeting thalamic circuits rescues motor and mood deficits in PD mice. Nature. 2022; 607 (7918): 321–329. https://doi.org/10.1038/s41586-022-04806-x

18.