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

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.