A single-arm, open-label pilot study of neuroimaging, behavioral, and peripheral inflammatory correlates of mindfulness-based stress reduction in multiple sclerosis

Abstract

Multiple sclerosis (MS) is a chronic neurological disease frequently associated with significant fatigue, anxiety, depression, and stress. These symptoms are difficult to treat, and prominently contribute to the decreases in quality of life observed with MS. The underlying mechanisms of these "silent" symptoms are not well understood and include not just the psychological responses to a chronic disease, but also biological contributions from bidirectional psycho-neuro-immune (dys)regulation of systemic inflammatory biology. To address these issues, we conducted a prospective, observational pilot study to investigate the psychological, biological, and neuroarchitecture changes associated with a mindfulness-based stress reduction (MBSR) program in MS. The overarching hypothesis was that MBSR modulates systemic and central nervous system inflammation via top-down neurocognitive control over forebrain limbic areas responsible for the neurobiological stress response. 23 patients were enrolled in MBSR and assessed pre/post-program with structural 3 T MRI, behavioral measures, hair cortisol, and blood measures of peripheral inflammation, as indexed by the Conserved Transcriptional Response to Adversity (CTRA) profile. MBSR was associated with improvements across a variety of behavioral outcomes, as well as on-study enlargement of the head of the right hippocampus. The CTRA analyses revealed that greater inflammatory gene expression was related to worse patient-reported anxiety, depression, stress, and loneliness, in addition to lower eudaimonic well-being. Hair cortisol did not significantly change from pre- to post-MBSR. These results support the use of MBSR in MS and elucidate inflammatory mechanisms related to key patient-reported outcomes in this population.

Keywords: Conserved transcriptional response to adversity; Hair cortisol; Mindfulness-based stress reduction; Multiple sclerosis; Patient reported outcomes; Perceived stress.

Figure 1

Hippocampal head volume is observed to be larger following MBSR. Violin plot showing group pre-post enlargement in right hippocampal head volume, unadjusted for covariates. The p-value listed is adjusted for age, intracranial volume and intra-subject correlation.

Figure 2

Hippocampal subsegmentation with coronal (top row), axial (middle row) and sagittal (bottom row) sections through the hippocampus. Column A is unlabeled, Column B is labeled with head/body/tail, with 3D enlargement in section C. Column E is labeled using Freesurfer hippocampal subsegmentation, with a coronal cross-section enlarged in box D.