The Role of Personality at Multiple Sclerosis Onset: Impact on Clinical and Biomarkers Outcomes

Background Multiple sclerosis (MS) is a chronic autoimmune, inflammatory, and neurodegenerative disease of the central nervous system. Beyond its classical neurological manifestations, MS is increasingly recognized as a multidimensional clinical condition characterized by significant psychiatric and cognitive involvement, which contribute substantially to overall disease burden from the earliest stages of the disease. Within this framework, personality traits may represent a relevant dimension underlying individual differences in emotional vulnerability, psychological adaptation, and clinical expression. At the same time, neurofilament light chain (NfL), as a biomarker of neuroaxonal damage, provides a potential link between biological and psychological dimensions in early MS, although the relationship between personality traits and markers of neuronal injury remains insufficiently explored. Objectives The present study aimed to investigate the role of personality traits at the time of MS diagnosis within an integrated clinical, cognitive, psychological, and biological framework. Specifically, the study examined: (i) the associations between personality traits and emotional symptoms, cognitive functioning, and health-related quality of life; (ii) the relationship between personality dimensions and objective indicators of disease burden, including neurological disability and NfL levels; and (iii) the extent to which personality traits contribute to variability in clinical, cognitive, and psychological outcomes. Methods This cross-sectional observational study included 100 patients aged ≥18 years with a diagnosis of relapsing multiple sclerosis (RMS) according to the revised McDonald criteria and with a highly active disease course. Patients were consecutively admitted between January 2024 and September 2025 and enrolled within 3 months from diagnosis. Patients with psychiatric or cognitive conditions interfering with the understanding of study procedures were excluded. Neurological disability was assessed using the Expanded Disability Status Scale (EDSS). Cognitive functioning was evaluated using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS), including the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test – Second Edition (CVLT-II), and the Brief Visuospatial Memory Test – Revised (BVMT-R). Personality traits were assessed using the Big Five Inventory (BFI). Depressive symptoms and anxiety were measured using the Beck Depression Inventory-II (BDI-II) and the State-Trait Anxiety Inventory (STAI-Y), respectively. Quality of life was assessed using the MSQoL-54. NfL levels were quantified in both cerebrospinal fluid and serum using standardized immunoassays. Descriptive statistics were computed for all demographic, clinical, cognitive, psychological, and biological variables. Associations were examined using partial Spearman correlations adjusted for age, sex, and education. Multivariable linear regression analyses were conducted to evaluate the independent contribution of personality traits to cognitive performance, emotional symptoms, and quality of life outcomes. Results Descriptive analyses did not indicate a markedly maladaptive personality profile in the sample. Clinically significant depressive symptoms were observed in 56% of patients, while elevated levels of state and trait anxiety were found in 38% and 56%, respectively. Cognitive impairment was detected in a minority of patients, ranging from 15% to 17% across cognitive domains. Personality traits showed selective and clinically meaningful associations across emotional, clinical, and quality of life domains. Higher neuroticism was associated with increased depressive symptoms (r = 0.39, p < 0.001), state anxiety (r = 0.33, p < 0.01), trait anxiety (r = 0.39, p < 0.001), greater neurological disability (EDSS; r = 0.31, p < 0.01), poorer physical quality of life (r = −0.25, p < 0.05), and poorer mental quality of life (r = −0.43, p < 0.001). Conversely, higher extraversion was associated with lower depressive symptoms (r = −0.35, p < 0.001), lower state anxiety (r = −0.43, p < 0.001), lower trait anxiety (r = −0.39, p < 0.001), and better mental quality of life (r = 0.32, p < 0.01). Higher conscientiousness was associated with lower depressive symptoms (r = −0.22, p < 0.05), lower trait anxiety (r = −0.23, p < 0.05), and better mental quality of life (r = 0.24, p < 0.05). With respect to cognitive functioning, only weak and domain-specific associations emerged, with neuroticism showing a positive association with verbal learning (CVLT-II; r = 0.21, p < 0.05) and a negative association with visuospatial memory (BVMT-R; r = −0.21, p < 0.05). No significant associations were observed for information processing speed (SDMT). No significant associations were found between personality traits NfL levels in either cerebrospinal fluid or serum. Multivariable regression analyses confirmed that higher neuroticism (β = 0.76, p < 0.001) and lower extraversion (β = −0.60, p = 0.004) were independently associated with trait anxiety. Depressive symptoms were primarily explained by trait anxiety (β = 0.55, p < 0.001), whereas mental quality of life was negatively associated with both depressive symptoms (β = −0.84, p = 0.001) and neuroticism (β = −0.91, p = 0.03). Personality traits did not independently predict cognitive performance, which was associated only with neurological disability (EDSS; β = −0.19, p = 0.03). Conclusions At the time of diagnosis, personality traits in patients with MS do not indicate a markedly maladaptive personality profile. However, specific personality dimensions, particularly higher neuroticism and lower extraversion, show meaningful associations with emotional symptoms and quality of life. These findings suggest that personality traits may represent dimensions of individual vulnerability, contributing to variability in the psychological and clinical expression of the disease from its earliest stages. At the same time, the absence of marked alterations at diagnosis supports the hypothesis that potential changes in personality may emerge over the course of disease progression, possibly in relation to both neurobiological and psychosocial factors. Within this framework, the relationship between personality, emotional symptoms, and clinical features appears to be complex and potentially bidirectional, reflecting a dynamic interplay rather than a unidirectional effect. The lack of association with NfL highlights the need for further investigation into the biological underpinnings of these processes, while the observed domain-specific cognitive findings suggest that the interaction between personality and cognition in multiple sclerosis remains only partially understood. Overall, these findings underscore the importance of further exploring the role of personality traits in MS through longitudinal and multimodal approaches, in order to better clarify their evolution over time and their interaction with cognitive and neurobiological processes.