A Longitudinal Transdiagnostic Cognitive Model of Depression and Anxiety in Chronic Inflammatory Disease: Evidence from Multiple Sclerosis and Endometriosis

Objective: Clinical levels of depressive and anxiety symptoms are prevalent in Multiple Sclerosis (MS) and Endometriosis (EMS), yet their underlying mechanisms remain poorly understood. Guided by a transdiagnostic cognitive framework (Nolen-Hoeksema & Watkins, 2011), this study examined whether anxiety sensitivity, intolerance of uncertainty, distress tolerance, and rumination mediate the pathways between neuroticism and depressive and anxiety symptoms. Further, pain severity in EMS and gait-disability may represent contextual moderators of factor-symptom relationships. Methods: Population-based cohorts of individuals with MS (T1, baseline: n= 229; T2, 6-month follow-up: n= 134) and EMS (T1, n= 399; T2, n= 130) completed online surveys at two-time points. Adopting a path-analytic approach, the relationships between neuroticism, cognitive factors, and depressive and anxiety symptoms were evaluated cross-sectionally and prospectively within an integrated model. Gender and age were included as covariates. Pain severity in EMS, and gait disability in MS, were examined as moderating factors. Structural invariance testing explored the plausibility of a common model among diseases. Results: Cross-sectionally, distress tolerance and rumination emerged as the most consistent mediators, with the largest effect for distress tolerance in the relationship between neuroticism and depressive symptoms in the MS group ( ß =.17, 95% CI: .02, .33). Anxiety sensitivity and intolerance of uncertainty demonstrated symptom- and disease-specific associations. Longitudinally, lower distress tolerance mediated the association between neuroticism and later anxiety symptoms in MS ( ß =.10, 95% CI: .04, .17), whereas in EMS, distress tolerance and anxiety sensitivity showed small indirect effects in the depressive pathway. No interaction effects were detected. Although structural non-invariance was observed, substantial convergence in trait–factor and factor–symptom associations was evident across diseases. Conclusions: The principal finding identified distress tolerance as a transdiagnostic cognitive factor linking neuroticism with affective symptoms, underscoring its therapeutic relevance and suggesting shared psychological mechanisms across MS and EMS. Findings extend an emerging evidence-base of cross-disease parallels into the psychological domain.