Full Papers
Interleukin-1 receptor accessory protein expression could link to the insula-default mode network connection and clinical depression in fibromyalgia: a preliminary exploratory study
N.T. Nhu1, S.-Y. Wang2, C.-L. Han3, J.-H. Kang4
- International PhD Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; and Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho, Vietnam.
- Master Program in Clinical Genomics and Proteomics, College of Pharmacy, Taipei Medical University, Taipei; Department of Pharmaceutical Sciences, School of Pharmacy, Taipei Medical University, Taipei; and PhD Program in Drug Discovery and Development Industry, Taipei Medical University, Taipei, Taiwan.
- Master Program in Clinical Genomics and Proteomics, College of Pharmacy, Taipei Medical University, Taipei; Department of Pharmaceutical Sciences, School of Pharmacy, Taipei Medical University, Taipei; and PhD Program in Drug Discovery and Development Industry, Taipei Medical University, Taipei, Taiwan.
- International PhD Program in Medicine, College of Medicine, Taipei Medical University, Taipei; Department of Physical Medicine and Rehabilitation, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Physical Medicine and Rehabilitation, Taipei Medical University Hospital, Taipei; and Graduate Institute of Nanomedicine and Medical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan. jhk@tmu.edu.tw
CER19238
Full Papers
PMID: 41678182 [PubMed]
Received: 25/08/2025
Accepted : 19/12/2025
In Press: 26/01/2026
Abstract
OBJECTIVES:
The expression of interleukin-1 receptor accessory protein (IL-1RAP) and connections between the anterior insula (AI) and the default mode network (DMN) regions might contribute to the heterogeneity of clinical depression in fibromyalgia (FM). This preliminary observational study provides early insight for a further large-scale study investigating the associations among IL-1RAP expression, AI-DMN connectivity, and clinical depression in FM.
METHODS:
We recruited seventeen FM patients and conducted clinical assessments, serum proteomic analysis, and magnetic resonance imaging (MRI) of the brain at baseline and 1-year follow-up. We analysed serum IL-1RAP expression from the proteomic analysis. With functional MRI data, we extracted the seed-based functional connectivity (FC) z-scores between the bilateral AI and DMN regions. We performed robust linear regressions among IL-1RAP, AI-DMN FCs, and the Beck Depression Index version II (BDI-II) scores. We performed ridge regressions to examine the impact of IL1RAP and AI-DMN FC interactions on BDI-II scores at baseline and follow-up.
RESULTS:
IL-1RAP expression significantly predicted the FC between the bilateral AI and posterior cingulate cortex (PCC). The right AI-PCC FCs negatively affect BDI-II scores. In addition, the negative effects of interactions between the IL-1RAP and the right AI-PCC FCs were significant at baseline but not at one-year follow-up.
CONCLUSIONS:
IL-1RAP could modulate depression through the AI and PCC connections in FM patients. The findings support further large-scale study to improve the understanding of symptomatic heterogeneity in FM.
