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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. (2023): The multimodal Munich Clinical Deep Phenotyping study to bridge the translational gap in severe mental illness treatment research. Frontiers in Psychiatry, 14: 1179811. ISSN 1664-0640

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Introduction: Treatment 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.

Methods: In 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.

Results: Here, 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.

Discussion: The 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.

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