Project Details
Projekt
Biopsychosocial and Healthcare-related Predictors of Persistent Somatic Symptoms in Patients with Unclear Diagnosis at a Rare Disease Centre: a Prospective Observational Study (SOMA.RARE)
Applicants
Dr. Fabian Braun; Dr. Natalie Uhlenbusch
Subject Area
Public Health, Healthcare Research, Social and Occupational Medicine
Term
since 2026
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 445297796
Rare diseases affect about 400-500 million people worldwide and are defined by a prevalence of no more than 1:2000. Differentiating these disorders from more common somatic or psychiatric conditions is challenging, often leading to prolonged diagnostic pathways and misdiagnoses. Centers for Rare Diseases (RDC) provide a structured evaluation of patients with suspected rare diseases. Individuals presenting at RDCs frequently report nonspecific symptoms such as fatigue, pain, or muscle weakness. SOMA.RARE will be integrated as a new project into the second funding phase and aims to validate transdiagnostic factors identified by SOMACROSS.1 in this heterogeneous group. Studies by us and others indicate that this patient group experiences high levels of psychological distress. In addition to the unclear somatic symptoms, psychosocial factors (illness-related anxiety, negative expectations, or previous adverse experiences) substantially shape patients’ well-being. The moment of receiving a diagnosis is often described as an ambivalent turning point, which may strongly influence both symptom perception and psychological state. We hypothesize several possible explanations for the persistence of symptoms: undetected diseases, transdiagnostic biomedical mechanisms (e.g., inflammatory markers like soluble urokinase plasminogen activator receptor (suPAR) or alterations in the microbiome), psychosocial factors (e.g. depression, expectations), as well as healthcare-related aspects (e.g. prolonged “diagnostic odyssey”). SOMA.RARE will address central gaps in care: its objective is to advance understanding of how biomedical, psychosocial, and healthcare-related factors influence the severity and persistence of somatic symptoms. Based on the SOMACROSS conceptual model, predictors of symptom persistence will be investigated including biomedical variables (suPAR and microbiome) as well as psychosocial factors (depressive symptoms, symptom-related distress, and expectations). In addition, the study will examine to what extent the access to specialized assessment by a RDC and (not) receiving a diagnosis influences the symptom trajectory of persistent physical symptoms. We plan a prospective 12-month cohort study to validate biopsychosocial predictors of persistent somatic symptoms (PSS). This will be complemented by an ecological momentary assessment (EMA) study, capturing symptom fluctuations over 14 days before and after the diagnostic disclosure, and a longitudinal qualitative study examining patient trajectories and healthcare experiences through interviews and journaling. SOMA.RARE will validate and extend the conceptual model further focusing on healthcare-related factors with a particular emphasis on the moment of diagnosis. The results will guide both the care and assessment of patient with suspected rare diseases as well as those with common conditions in the future.
DFG Programme
Research Units
