A novel ecological approach to assess theory of Mind and social norm understanding for social cognition phenotyping in multiple sclerosis.

Social cognition (SC) impairment is a hallmark of the cognitive profile in Multiple Sclerosis (MS). However, there is a still no consensus on recommended measures for SC phenotyping in this clinical population, limiting our understanding of underlying mechanism and the development of targeted intervention. This study evaluated the suitability of the Edinburgh Social Cognition test (ESCoT), a novel ecologically valid tool assessing affective (ToMA) and cognitive (ToMc) Theory of Mind, as well as interpersonal (SNUINTER) and intrapersonal (SNUINTRA) social norm understanding, for SC phenotyping in MS. Seventy-one participants (39 with MS and 32 healthy controls) completed a neuropsychological battery including both non-social (Stroop test, Digit Span) and socio-cognitive (Eyes Test, ESCoT) measures. ESCoT demonstrated strong diagnostic validity (AUC = 0.803), outperforming the Eyes test (AUC = 0.653). Notably, ESCoT captured the peculiarity SC impairment profile in MS, marked by a dissociation between affective and cognitive ToM (ToMA< ToMc; group*ToM domain interaction: F = 21.87, p < 0.001), and between interpersonal and intrapersonal SNU (SNUINTER< SNUINTRA: group*SNU domain interaction: F = 22.76, p < 0.001). In the MS group, ToMA and ToMc scores were associated with the working memory, while SNUINTRA score was linked to executive functioning. These findings support ESCoT as a valid tool for SC phenotyping in MS.