Background & Aims

Pain, depression, and fatigue are highly comorbid and prevalent symptoms. Importantly, this symptom cluster has been associated with increased suffering and poor treatment outcomes. The underlying brain mechanisms are only partially understood, but a common etiology has been proposed (Heitmann et al., 2022). However, transdiagnostic biomarkers are lacking. Insights into brain function in pain, depression, and fatigue will aid the understanding of this comorbidity. Moreover, developing transdiagnostic biomarkers could further the diagnosis and treatment of this symptom cluster (Scangos, State, Miller, Baker, & Williams, 2023; Woo, Chang, Lindquist, & Wager, 2017) in line with the National Institutes of Mental Health (NIMH) Research domain criteria (RDoC) approach (Insel et al., 2010).

Methods

To summarize the current knowledge on electrophysiological brain correlates of chronic pain, depression, and fatigue, we performed a series of preregistered systematic literature reviews (PROSPERO: CRD42021272622, CRD42022330113) in accordance with PRISMA-Guidelines (Page et al., 2021). MEDLINE, Web of Science Core Collection, and EMBASE were searched for quantitative resting-state electroencephalography (EEG) studies in adult patients suffering from each of these symptoms separately.

Results

The systematic reviews in patients suffering from chronic pain and fatigue have been finalized and included 76 and 26 studies, respectively. For both symptoms, cross-sectional studies revealed an increase in theta band power compared to healthy participants. Results for depression patients are pending. Risk of bias was assessed with a modified Newcastle-Ottawa Scale, and was considerably high in all of the systematic reviews.

Conclusions

These findings point towards increased theta oscillations, which have also previously been described in depression, as a transdiagnostic biomarker for the symptom cluster of pain, depression, and fatigue. The use of theta oscillations to diagnose, monitor and eventually also treat this burdensome comorbidity, e.g. using neuromodulation techniques, should be further evaluated.

References

Heitmann, H., Andlauer, T. F. M., Korn, T., Muhlau, M., Henningsen, P., Hemmer, B., & Ploner, M. (2022). Fatigue, depression, and pain in multiple sclerosis: How neuroinflammation translates into dysfunctional reward processing and anhedonic symptoms. Mult Scler, 28(7), 1020-1027. doi:10.1177/1352458520972279

Insel, T., Cuthbert, B., Garvey, M., Heinssen, R., Pine, D. S., Quinn, K., . . . Wang, P. (2010). Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am J Psychiatry, 167(7), 748-751. doi:10.1176/appi.ajp.2010.09091379

Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., . . . Moher, D. (2021). The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Syst Rev, 10(1), 89. doi:10.1186/s13643-021-01626-4

Scangos, K. W., State, M. W., Miller, A. H., Baker, J. T., & Williams, L. M. (2023). New and emerging approaches to treat psychiatric disorders. Nat Med, 29(2), 317-333. doi:10.1038/s41591-022-02197-0

Woo, C. W., Chang, L. J., Lindquist, M. A., & Wager, T. D. (2017). Building better biomarkers: brain models in translational neuroimaging. Nat Neurosci, 20(3), 365-377. doi:10.1038/nn.4478

Presenting Author

Henrik Heitmann

Poster Authors

Henrik Heitmann

MD

Technische Universität München

Lead Author

E-mail

Jean-Francois Siani

Technical University of Munich, Department of Neurology

Lead Author

E-mail

Paul Theo Zebhauser

University Hospital of the Klinikum rechts der Isar, Technical University Munich

Lead Author

E-mail

Vanessa D. Hohn

PhD

Technical University of Munich, Department of Neurology

Lead Author

E-mail

Peter Henningsen

Professor

Technical University of Munich, Department of Psychosomatic Medicine and Psychotherapy

Lead Author

E-mail

Stefan Leucht

Professor

Technical University of Munich, Department of Psychiatry

Lead Author

E-mail

Josef Priller

Professor

Technical University of Munich, Department of Psychiatry

Lead Author

E-mail

Markus Ploner

Technische Universitaet Munchen

Lead Author

E-mail

Topics

  • Pain Imaging