Feasibility of the Development and Psychometric Properties of a Standardized Screening Instrument for Mental Disorders in Patients with Suspected Rare Diseases: Results of the ZSE-DUO Study

Lilly Sophia Brandstetter^1*Kathrin Ungethüm^1,2Peter U Heuschmann^1,2,3Lisa Pfister⁴Jürgen Deckert^5,6Martina De Zwaan⁷Oliver Tüscher⁸Stefanie Witt⁹Christian Krauth¹⁰Alexandra Berger¹¹Mark Berneburg¹²Anna Deibele¹³Jan Dieris-Hirche¹⁴Gereon Heuft¹⁵Christiane Imhof¹⁶Jörg Schulz^17,18Stephan Zipfel¹⁹Helge Hebestreit^20,4Kirsten Haas¹ZSE-DUO Working Group ZSE-DUO Working Group²¹

• ¹Institute for Clinical Epidemiology and Biometry, Julius Maximilian University of Würzburg, Würzburg, Germany
• ²Institute for medical Data Science, University Hospital Würzburg, Würzburg, Germany
• ³University Hospital Würzburg, Clinical Trial Centre Würzburg, Würzburg, Germany
• ⁴Centre for Rare Diseases, University Hospital Würzburg, Würzburg, Germany
• ⁵Clinical Trial Centre Würzburg, University Hospital Würzburg, Würzburg, Germany
• ⁶University Hospital Würzburg, Department of Psychiatry, Psychosomatics and Psychotherapy, Würzburg, Germany
• ⁷Department of Psychosomatic Medicine and Psychotherapy, Hannover Medical School, Hannover, Germany
• ⁸Department of Psychiatry and Psychotherapy, University Medical Center Mainz, Mainz, Germany
• ⁹Center for Psychosocial Medicine, Department of Medical Psychology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
• ¹⁰Centre for Health Economics Research Hannover and Institute for Epidemiology, Social Medicine and Health Systems Research, Hannover Medical School, Hannover, Germany
• ¹¹Frankfurt Reference Centre for Rare Diseases, University Hospital Frankfurt, Goethe-University Frankfurt, Frankfurt, Germany
• ¹²Centre for Rare Diseases Regensburg, University Hospital Regensburg, Regensburg, Germany
• ¹³Department of Psychosomatic Medicine and Psychotherapy, University Hospital Magdeburg, Magdeburg, Germany
• ¹⁴Department of Psychosomatic Medicine and Psychotherapy, LWL-University Hospital, Ruhr University Bochum, Bochum, Germany
• ¹⁵Department of Psychosomatic Medicine Und Psychotherapy, University Hospital Münster, Münster, Germany
• ¹⁶Department of Psychosomatic Medicine and Psychotherapy, Ulm University Medical Center, Ulm, Germany
• ¹⁷Department of Neurology, RWTH Aachen University, Aachen, Germany
• ¹⁸Center for Rare Diseases, Medical Faculty, RWTH Aachen University, Aachen, Germany
• ¹⁹Department of Psychosomatic Medicine and Psychotherapy, University of Tübingen, Tübingen, Germany
• ²⁰University Hospital Würzburg, Department of Pediatrics, Würzburg, Germany
• ²¹Members of the working group are listed in the Supplement table 1, Würzburg, Germany

Introduction Patients presenting in Centres for Rare Diseases (CRD) show complex symptoms, requiring multiprofessional expertise. Many patients suffer from unnoticed mental disorders. Currently, mental health experts (MHE) are rarely involved in the diagnostic process. The aim of this study was to test the feasibility of developing a new short screening instrument for mental disorders and to test its predictive value. Methods Data were derived from 1300 adult patients participating in ZSE-DUO (Dual guidance structure in Centres for Rare Diseases), a multicentre study in 11 CRD (funding by G-BA, Grant 01NVF17031), evaluating the benefit of involving a MHE in the diagnostic process. Patients completed standardized questionnaires on anxiety (GAD-7), depression (PHQ-9), dissociation (DSS-4), psychopathology (SCL-K-9) and quality of life (SF-12, EQ-5D-5L) prior to and during their first CRD visit as part of the routine assessment necessary for a first contact at a CRD. Explorative factor analysis (EFA) was performed for item reduction. Reliability of the factor structure was assessed by Cronbach's α. Model fit was tested using confirmatory factor analysis (CFA). The predictive value of the new screening instrument was tested by calculating a receiver operating characteristic (ROC) curve using the diagnoses from the MHE. Results The extracted 18-item model had a 4-factor structure with acceptable to high reliability. The extracted mental health dimensions were: (1) anxiety and depression, (2) mobility and activities of daily living, (3) energy or fatigue, and (4) dissociation. Excluding the dimension 'dissociation' (well assessed by the DSS-4 separately), a summary score was calculated ranging from 0-45, with the lowest score representing the best mental health. In the CFA, the model fit indices for the extracted factor structure