Altered cerebral blood flow covariance networks in premenstrual syndrome and the association of resting state functional connectivity with peripheral cytokine profiles

Premenstrual syndrome (PMS) has been associated with altered central nervous system function and peripheral inflammation, but how multivariate cytokine profiles relate to functional interactions between brain regions remains unclear. We examined multimodal neuroimaging abnormalities and their associations with multivariate peripheral cytokine patterns in PMS. In this cross-sectional study, 54 women with PMS and 71 healthy controls (HCs) underwent arterial spin labeling (ASL) and resting-state functional MRI (rs-fMRI) and completed prospective Daily Record of Severity of Problems (DRSP) ratings. MRI acquisition and peripheral blood sampling were performed during the late luteal phase. Cerebral blood flow (CBF) covariance network analysis and rs-fMRI functional connectivity (FC) were used to characterize brain alterations. Principal component analysis was used to derive serum cytokine component scores, and their associations with imaging measures and DRSP total and symptom domain scores were examined. PMS participants showed altered CBF covariance network properties and lower right supplementary motor area–pregenual anterior cingulate cortex FC than HCs ( p < 0.05, TFCE-FWE corrected). A two-component solution explained 65.4% of the variance. Within PMS, the second rotated component (RC2) was positively associated with FC (β = 0.062, 95% CI 0.015 to 0.110, Bonferroni-adjusted p = 0.022). Neither rotated component nor any individual cytokine was significantly associated with DRSP total or symptom domain scores after Bonferroni correction. A multivariate peripheral cytokine component was associated with altered functional connectivity in PMS, whereas cytokine measures showed no robust associations with symptom severity. Longitudinal studies are needed to determine the temporal and clinical relevance of peripheral cytokine associations with brain function across the menstrual cycle. Chinese Clinical Trial Registry (ChiCTR1900020642), registered on 11 January 2019.