The Association Between Intracortical Myelin and Depressive Symptom Severity in Mood Disorders

Abstract

Depression ranks amongst the most prevalent psychiatric disorders worldwide, yet its etiology remains unclear. One potential causative factor involves disruptions in the central nervous system’s neurobiology, particularly in the cerebral cortex. Emerging evidence from animal, human postmortem, and preliminary imaging studies indicates that disruptions in myelin of the cerebral cortex (intracortical myelin) are associated with either the presence of depressive symptoms or a major depressive disorder (MDD) diagnosis. Further studies are needed to robustly verify the relationship between intracortical myelin disruptions and depressive symptomatology in humans. This thesis studied 47 individuals with mood disorders and 8 healthy controls. Participants were recruited and characterized through a master clinical trial platform on mood disorders. Whole-brain quantitative magnetic resonance imaging (qMRI) measurements were made at 3 Tesla across cortical regions of R₁ relaxation rate, a surrogate marker of intracortical myelin. Depressive symptom severity was evaluated using the 10-item Montgomery–Åsberg Depression Rating Scale (MADRS). The relationship between R₁ and depressive symptom severity was modelled using a general linear model: R₁ ~ age + age² + sex + MADRS. Analysis revealed medium effect sizes (partial η²) in several cortical regions for the MADRS term, after controlling for age and sex. Findings were not statistically significant following FDR correction. The strongest effect sizes were observed in areas of the prefrontal, cingulate, orbitofrontal, insular, hippocampal and parietal cortices, consistent with findings from alternative modalities implicating these regions in depression. These findings provide emerging evidence of an association between intracortical myelin and depressive symptom severity, bolstering existing research identifying intracortical myelin abnormalities in mood disorders. Overall, this thesis contributes to the early mapping of depressive severity-related cortical myelin changes and lays the foundation for future hypothesis-driven, large-scale investigations. Elucidating the involvement of intracortical myelin in depressive symptomatology could offer crucial insights into the neurobiological mechanisms underlying depressive pathology.