Blunted neural and psychological stress processing predicts future grey matter atrophy in multiple sclerosis

BACKGROUND: Multiple sclerosis (MS) is characterized by two neuropathological key aspects: inflammation and neurodegeneration. Clinical studies support a prospective link between psychological stress and subsequent inflammatory disease activity. However, it is unknown if a similar link exists for grey matter (GM) degeneration as the key driver of irreversible disability. METHODS: We tested whether neural network activity triggered in a psychological fMRI stress paradigm (a mental arithmetic task including social evaluation) conducted at a baseline time point predicts future GM atrophy in 25 persons with MS (14 females). Atrophy was determined between the baseline and a follow-up time point with a median delay of 1012 (Rg: 717–1439) days. Additionally, atrophy was assessed in 22 healthy subjects (13 females; median delay 771 [Rg: 740–908] days between baseline and follow-up) for comparison. RESULTS: An analysis of longitudinal atrophy in patients revealed GM loss in frontal, parietal, and cerebellar areas. Cerebellar atrophy was more pronounced in patients than controls. Future parietal and cerebellar atrophy could be predicted based on activity of two networks. Perceived psychological stress was negatively related to future parietal atrophy in patients and activity of the network predictive of parietal atrophy was positively linked to perceived stress. CONCLUSIONS: We have shown that blunted neural and psychological stress processing have a detrimental effect on the course of MS and are interrelated. Together with research showing that psychological and neural stress processing can be altered through interventions, our findings suggest that stress processing might constitute an important modifiable disease factor.