A transdiagnostic cognitive model of depression and anxiety in chronic inflammatory disease: Evidence from multiple sclerosis and endometriosis

Objective Depressive and anxiety symptoms are prevalent in Multiple Sclerosis (MS) and Endometriosis (EMS), yet their underlying processes remain poorly understood. Guided by a transdiagnostic framework (Nolen-Hoeksema & Watkins, 2011), this study examined anxiety sensitivity, intolerance of uncertainty, distress tolerance, and rumination as mediators of the pathways between neuroticism and depressive and anxiety symptoms. Further, pain severity in EMS and gait-disability in MS were examined as 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. The relationships between neuroticism, cognitive factors, and affective symptoms were evaluated cross-sectionally and prospectively within an integrated path model. Structural invariance testing explored the plausibility of a common model. Results Cross-sectionally, distress tolerance and rumination emerged as consistent mediators, with the largest effect for distress tolerance in the depressive pathway in the MS group (ß = 0.17, 95% CI: 0.02, 0.33). Anxiety sensitivity and intolerance of uncertainty demonstrated symptom- and disease-specific associations. Longitudinally, distress tolerance mediated the relationship between neuroticism and residualised change in anxiety symptoms in MS (β = 0.10, 95% CI: 0.04, 0.17), whereas in EMS, distress tolerance and anxiety sensitivity showed indirect effects in the depressive pathway. No interaction effects were detected. Although structural non-invariance was observed, substantial convergence in pathways was observed across diseases. Conclusions Distress tolerance is a candidate transdiagnostic factor linking neuroticism with affective symptoms, underscoring its therapeutic relevance. Findings extend an emerging evidence-base of cross-disease parallels into the psychological domain.