Exploring the complexities of social cognition in Multiple Sclerosis: interplay between bio‑psycho‑social factors

Multiple sclerosis (MS) is often associated with social-cognitive difficulties. Whether disease-related factors (e.g., inflammation or disease-modifying therapies (DMTs)) that alter these factors) and sleep quality (a modifiable lifestyle factor), are related to social-cognitive functioning, is not known. Inflammatory biomarkers associated with the innate immune system and the brain’s kynurenine pathway have attracted interest as potential prognostic biomarkers in MS diagnosis. In MS, dysregulation of innate immunity and the kynurenine pathway can lead to increased production of pro-inflammatory cytokines (e.g., IL-1β and TNF-α), and the increased production of neurotoxic metabolites (e.g., 3-hydroxy-kynurenine and quinolinic acid), which contribute to demyelination and neuronal damage in MS. While some studies have explored the link between inflammation and social cognition, findings have been inconclusive, owing partly to methodological limitations (e.g., small sample sizes). Both disease-modifying therapy use and sleep quality are modifiable factors that may improve social-cognitive functioning in MS. It may achieve this directly through better expression and activity of pro-inflammatory cytokines, which in turn may facilitate better neural processing in regions of the ‘social brain’ (the network of neurons supporting social-cognitive function), or indirectly through increased social engagement (i.e., stemming from an improvement in overall wellbeing). DMTs exert immunomodulatory effects through their ability to reduce inflammation in the central nervous system. Sleep plays a crucial role in regulating immune function and modulating inflammatory signalling pathways.
Using a bio-psycho-social approach, the aims of the current thesis are twofold: (1) to examine the relationship between potential prognostic biomarkers associated with MS (i.e., inflammatory cytokines and the brain’s kynurenine pathway) and social-cognitive functioning; and (2) to examine whether modifiable factors of DMTs and sleep, which may alter MS-related disease biomarkers, are related to social functioning and/or social?cognitive functioning. The thesis comprised four studies. Study 1 examined the impact of inflammatory biomarkers on social-cognitive functioning. Study 2 investigated the impact of kynurenine pathway metabolites on social-cognitive functioning. The third study examined the link between DMTs and sleep on functional outcomes related to daily activity engagement and social functioning, and the final study examined the impact of sleep quality on social-cognitive ability. The key findings of this thesis, are: (1) pro-inflammatory cytokines and neurotoxic biomarkers are related to poorer social cognition; (2) anti?inflammatory cytokines and neuroprotectant biomarkers are associated with better social cognition; (3) DMTs do not affect subjective sleep quality, activity engagement, or social functioning, but beliefs about DMT use were associated with poorer sleep quality and increased interference in daily functioning; and (4) sleep quality is not associated with social cognition; however, there is an association between increased daytime sleepiness and emotion recognition.
Overall, the findings of a link between both pro-inflammatory cytokines and kynurenine pathway metabolites and social-cognitive functioning, suggest that targeted therapies may be a future possibility help to improve social-cognitive functioning and social engagement in people with MS. Pharmacological interventions targeting neuroinflammation could help to reduce the release of pro-inflammatory cytokines, improve neural plasticity, and in turn, social-cognitive abilities. Cognitive-behavioural therapy may aid in altering negative perceptions that individuals with MS hold regarding the influence of DMT use on sleep outcomes and its consequences on social functioning and daily activities. This thesis contributes to the literature in a range of disciplines, including biomedicine, immunology, and psychology.