The effects of disease activity, inflammation, depression and cognitive fatigue on resting state fMRI in systemic lupus erythematosus

Objectives Cognitive dysfunction (CD) and depression are interlinked comorbidities of SLE. They may be the result of altered brain mechanisms. This study aimed to examine SLE effects on functional connectivity (FC) within the default mode network (DMN) using resting state fMRI, and how depression may impact this. Methods Demographic, clinical and psychiatric data were collected from 19 SLE-active, 23 SLE-stable and 30 healthy controls (HC) participants. A T2*-weighted rsfMR scan was acquired and analysed using independent component analysis. Group z-scores for nodes associated with the DMN were tested. Significant nodes were entered into a factor analysis. The combined factor was used in correlations with factors of interest. Significant variables were used in a mediation analysis. Results 14 DMN nodes were defined using independent component analysis. In five nodes, the SLE groups had significantly reduced FC compared with the HC group (P < 0.01). Factor analysis generated one factor that only depression score correlated with for both the HC group (r(s) = -0.510) and SLE groups combined (r(s) = -0.390). Mediation analysis revealed depression score accounted for 22% of the altered FC in the DMN. Disease state accounted for the remaining 78%. Conclusions Altered FC was evident in DMN nodes for SLE groups irrespective of disease activity. Depression accounts for some of this effect but SLE directly accounted for more. Further studies are needed to assess if these changes may be a precursor to CD in SLE. If so, rs-fMRI could be an early marker for CD in SLE and help in future CD in SLE treatment trials.