Frontiers in Psychiatry (May 2023)

The multimodal Munich Clinical Deep Phenotyping study to bridge the translational gap in severe mental illness treatment research

  • Lenka Krčmář,
  • Lenka Krčmář,
  • Iris Jäger,
  • Emanuel Boudriot,
  • Katharina Hanken,
  • Vanessa Gabriel,
  • Julian Melcher,
  • Nicole Klimas,
  • Fanny Dengl,
  • Susanne Schmoelz,
  • Pauline Pingen,
  • Mattia Campana,
  • Joanna Moussiopoulou,
  • Vladislav Yakimov,
  • Georgios Ioannou,
  • Sven Wichert,
  • Silvia DeJonge,
  • Peter Zill,
  • Boris Papazov,
  • Valéria de Almeida,
  • Sabrina Galinski,
  • Nadja Gabellini,
  • Genc Hasanaj,
  • Matin Mortazavi,
  • Temmuz Karali,
  • Alexandra Hisch,
  • Marcel S Kallweit,
  • Verena J. Meisinger,
  • Lisa Löhrs,
  • Karin Neumeier,
  • Stephanie Behrens,
  • Susanne Karch,
  • Benedikt Schworm,
  • Christoph Kern,
  • Siegfried Priglinger,
  • Berend Malchow,
  • Johann Steiner,
  • Johann Steiner,
  • Johann Steiner,
  • Johann Steiner,
  • Alkomiet Hasan,
  • Frank Padberg,
  • Oliver Pogarell,
  • Peter Falkai,
  • Peter Falkai,
  • Andrea Schmitt,
  • Andrea Schmitt,
  • Elias Wagner,
  • Daniel Keeser,
  • Daniel Keeser,
  • Daniel Keeser,
  • Florian J. Raabe,
  • Florian J. Raabe,
  • Florian J. Raabe

DOI
https://doi.org/10.3389/fpsyt.2023.1179811
Journal volume & issue
Vol. 14

Abstract

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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.

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