The multimodal Munich Clinical Deep Phenotyping study to bridge the translational gap in severe mental illness treatment research
Authors: Krčmář Lenka , Jäger Iris , Boudriot Emanuel , Hanken Katharina , Gabriel Vanessa , Melcher Julian , Klimas Nicole , Dengl Fanny , Schmoelz Susanne , Pingen Pauline , Campana Mattia , Moussiopoulou Joanna , Yakimov Vladislav , Ioannou Georgios , Wichert Sven , DeJonge Silvia , Zill Peter , Papazov Boris , de Almeida Valéria , Galinski Sabrina , Gabellini Nadja , Hasanaj Genc , Mortazavi Matin , Karali Temmuz , Hisch Alexandra , Kallweit Marcel S , Meisinger Verena J. , Löhrs Lisa , Neumeier Karin , Behrens Stephanie , Karch Susanne , Schworm Benedikt , Kern Christoph , Priglinger Siegfried , Malchow Berend , Steiner Johann , Hasan Alkomiet , Padberg Frank , Pogarell Oliver , Falkai Peter , Schmitt Andrea , Wagner Elias , Keeser Daniel , Raabe Florian J. 
Published: May 2023

IntroductionTreatment of severe mental illness (SMI) symptoms, especially negative symptoms and cognitive dysfunction in schizophrenia, remains a major unmet need. There is good evidence that SMIs have a strong genetic background and are characterized by multiple biological alterations, including disturbed brain circuits and connectivity, dysregulated neuronal excitation-inhibition, disturbed dopaminergic and glutamatergic pathways, and partially dysregulated inflammatory processes. The ways in which the dysregulated signaling pathways are interconnected remains largely unknown, in part because well-characterized clinical studies on comprehensive biomaterial are lacking. Furthermore, the development of drugs to treat SMIs such as schizophrenia is limited by the use of operationalized symptom-based clusters for diagnosis.MethodsIn line with the Research Domain Criteria initiative, the Clinical Deep Phenotyping (CDP) study is using a multimodal approach to reveal the neurobiological underpinnings of clinically relevant schizophrenia subgroups by performing broad transdiagnostic clinical characterization with standardized neurocognitive assessments, multimodal neuroimaging, electrophysiological assessments, retinal investigations, and omics-based analyzes of blood and cerebrospinal fluid. Moreover, to bridge the translational gap in biological psychiatry the study includes in vitro investigations on human-induced pluripotent stem cells, which are available from a subset of participants.ResultsHere, we report on the feasibility of this multimodal approach, which has been successfully initiated in the first participants in the CDP cohort; to date, the cohort comprises over 194 individuals with SMI and 187 age and gender matched healthy controls. In addition, we describe the applied research modalities and study objectives.DiscussionThe identification of cross-diagnostic and diagnosis-specific biotype-informed subgroups of patients and the translational dissection of those subgroups may help to pave the way toward precision medicine with artificial intelligence-supported tailored interventions and treatment. This aim is particularly important in psychiatry, a field where innovation is urgently needed because specific symptom domains, such as negative symptoms and cognitive dysfunction, and treatment-resistant symptoms in general are still difficult to treat.