Poster No:
411
Submission Type:
Abstract Submission
Authors:
Yann Quide1, Sylvia Gustin1
Institutions:
1UNSW Sydney, Sydney, NSW, Australia
First Author:
Co-Author:
Introduction:
Fibromyalgia is characterised by widespread pain for over three months that can arise in the absence of an evident organic lesion or injury. Elevated levels of anxiety and depression are often reported and associated with brain alterations (larger cerebellum, medial prefrontal/orbitofrontal cortices) in fibromyalgia. These alterations may result from neurobiological alterations common to these conditions, such as chronic elevated low-grade inflammation, altering the formation of myelin sheaths in the brain. However, the relationship between fibromyalgia, anxiety, depression, and brain myelination remains unknown. The present study aims to determine the brain myelination differences in females with fibromyalgia compared to females without fibromyalgia, and how these alterations are mediated by the severity of anxiety and depressive symptoms experienced.
Methods:
Participants were 33 females with fibromyalgia and 33 females without a chronic pain condition (Controls) from the ds004144 OpenNeuro dataset (Balducci et al., 2022). In addition to socio-demographical and fibromyalgia-related clinical information, severity of anxiety and depression were recorded using the Hamilton Depression Rating (HAMD) and Hamilton Anxiety Rating (HAMA) scales. Whole-brain three-dimensional T1-weighted (T1w) and T2-weighted (T2w) scans were acquired using a Philips 3T Ingenia scanner and processed using the default settings from the MRTool toolbox (Ganzetti et al., 2014). The T1w/T2w image was calculated as the ratio of the standardized T1w and T2w images. Whole-brain two-sample t-tests (using Statistical non-Parametric Mapping, SnPM13) was used to compare normalised T1w/T2w images between the groups. Age was added as covariate, and Family-wise error correction was applied to the cluster statistics (pFWEc<0.05). Raw signal at the peak of significant clusters was extracted for further analyses. Using linear regression models, associations between the extracted T1w/T2w values and severity of depression and anxiety were evaluated. Mediation analyses, using group as the independent variable, HAMD or HAMA total scores as mediators, and T1w/T2w values as dependent variables, were performed using the R package lavaan.
Results:
Compared to the control group, the fibromyalgia group lower T1w/T2w values in the left cerebellar lobule VI (peak MNI coordinates [-33,-35,-33], k=525 voxels, t(63)=5.34, pFWEc=0.030) and left cerebellar lobule VIII (peak MNI coordinates [-40,-41,-46], k=551 voxels, t(63)=5.01, pFWEc=0.029). These T1w/T2w values were significantly negatively associated with severity of anxiety (lobule VI: b=-0.010, p<0.001; lobule VIII: b=-0.007, p<0.001) and depressive symptoms (lobule VI: b= 0.010, p<0.001; lobule VIII: b=-0.008, p<0.001). Mediation analyses indicated that the severity of anxiety mediated the group difference in T1w/T2w values in cerebellar lobule VI (indirect effect: standardized b=-0.414, p=0.012), but not VIII (indirect effect: standardized b=0.045, p=0.813). Depressive symptoms did not significantly mediate the group differences in T1w/T2w values in cerebellar lobules VI and VIII.
Conclusions:
This study identified alterations in brain tissue properties (myelination) in females with fibromyalgia and clarified the role of anxiety and depression in these alterations. 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. Results also suggest a critical involvement of the cerebellum in affective processes, especially anxiety, in fibromyalgia. Replication in larger cohorts is necessary, and extension to other chronic pain conditions would inform on the generalisability of these findings.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Modeling and Analysis Methods:
Other Methods
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Neuroanatomy Other 2
Keywords:
Anxiety
Cerebellum
Myelin
Pain
STRUCTURAL MRI
1|2Indicates the priority used for review
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Please indicate below if your study was a "resting state" or "task-activation” study.
Other
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Patients
Was this research conducted in the United States?
No
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel?
NOTE: Any human subjects studies without IRB approval will be automatically rejected.
Yes
Were any animal research approved by the relevant IACUC or other animal research panel?
NOTE: Any animal studies without IACUC approval will be automatically rejected.
No
Please indicate which methods were used in your research:
Structural MRI
For human MRI, what field strength scanner do you use?
3.0T
Which processing packages did you use for your study?
SPM
Provide references using APA citation style.
Balducci, T., Rasgado-Toledo, J., Valencia, A., van Tol, M. J., Aleman, A., & Garza-Villarreal, E. A. (2022). A behavioral, clinical and brain imaging dataset with focus on emotion regulation of females with fibromyalgia (ds004144; Version 1.0.2) OpenNeuro. https://doi.org/10.18112/openneuro.ds004144.v1.0.0
Ganzetti, M., Wenderoth, N., & Mantini, D. (2014). Whole brain myelin mapping using T1- and T2-weighted MR imaging data. Front Hum Neurosci, 8, 671. https://doi.org/10.3389/fnhum.2014.00671
No