Divergent Myelination or Divergent Trajectories? Insights from MPF Mapping in Bipolar Disorder and Recurrent Depressive Disorder

Quantitative magnetic resonance imaging has increasingly highlighted white matter abnormalities as a key component of affective disorders. Fast macromolecular proton fraction (MPF) mapping, a myelin-sensitive technique, recently revealed divergent patterns of white matter myelination in bipolar disorder (BD) and recurrent depressive disorder (RDD), with reduced MPF in RDD but elevated MPF in BD. These findings challenge uniform hypomyelination models of mood disorders. In this Communication, we propose a trajectory-oriented reinterpretation of these results, suggesting that MPF differences may reflect distinct neurodevelopmental and lifespan-related myelination trajectories rather than a simple marker of tissue damage. Elevated MPF in BD-observed particularly in relatively young patients-may indicate accelerated or dysregulated white matter maturation or activity-dependent myelin plasticity, whereas reduced MPF in RDD may reflect impaired maintenance of myelin integrity. We emphasize that MPF should not be interpreted as a unidirectional index of pathology and argue that it may serve as a phenotype-differentiating biomarker between BD and RDD, warranting further longitudinal and multimodal studies.