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

Recent advances in quantitative MRI have renewed interest in white matter abnormalities as a potential neurobiological substrate of affective disorders, particularly as myelination is increasingly recognized as a dynamic and experience-dependent process. In this context, Gusakova et al. applied macromolecular proton fraction (MPF) mapping to compare global white matter myelination between bipolar disorder (BD) and recurrent depressive disorder (RDD), reporting reduced MPF in RDD alongside elevated MPF in BD. These findings challenge simplified deficit-based interpretations suggesting uniform hypomyelination across mood disorders. Here, we discuss the biological and clinical implications of divergent MPF profiles and propose a trajectory-based framework in which MPF differences may reflect altered timing, regulation, or rate of myelination across development rather than a single shared pathological endpoint. We emphasize that MPF should not be interpreted as a strictly unidirectional marker of white matter integrity, since elevated values may also represent compensatory or state-dependent processes. The observed divergence between BD and RDD highlights the potential of MPF mapping as a phenotype-differentiating biomarker and supports the need for longitudinal and multimodal neuroimaging studies integrating developmental factors, illness phase, and pharmacotherapy effects.