Fibromyalgia is associated with elevated levels of comorbid anxiety and depression, together impacting brain morphology possibly reflecting common underlying biological processes. The present study aims to determine the difference in regional myelination in females with fibromyalgia compared to females who do not experience chronic pain and determine the role of the severity of comorbid anxiety and depressive symptoms experienced to mediate this difference in brain myelination. Thirty-three females with and 33 females without (Controls) fibromyalgia were included, for which the severity of depressive and anxiety symptoms were recorded using the Hamilton Anxiety/Depression Rating scales (HAMA/HAMD). Whole-brain three-dimensional T1-weighted (T1w) and T2-weighted (T2w) magnetic resonance imaging scans were collected, and T1w/T2w ratio (myelin maps) derived. Mediation analyses were performed with anxiety and depressive symptoms as mediators of the T1w/T2w ratio differences among the groups. Compared to the control group, the fibromyalgia group lower T1w/T2w values in the left cerebellar lobule VI (pFWEc=0.030) and left cerebellar lobule VIII (pFWEc=0.029). These T1w/T2w values were significantly negatively associated with severity of anxiety and depressive symptoms (all p<0.001). Mediation analyses indicated that the severity of anxiety (but not depressive) symptoms mediated the group difference in T1w/T2w values in cerebellar lobule VI (p=0.012), but not VIII (p=0.813). Lowered cerebellar myelination may reflect chronic states of low-grade inflammation, resulting from the long-term consequences of living with fibromyalgia and related anxiety and depressive symptoms. This remains speculative, and future studies integrating peripheral biological markers of inflammation are warranted to confirm this interpretation.

The authors have declared no competing interest.

This work was supported by a Rebecca Cooper Fellowship from the Rebecca L. Cooper Medical Research Foundation awarded to S.M.G.

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