Concept of the Munich/Augsburg Consortium Precision in Mental Health for the German Center of Mental Health

Abstract

The Federal Ministry of Education and Research (BMBF) issued a call for a new nationwide research network on mental disorders, the German Center of Mental Health (DZPG). The Munich/Augsburg consortium was selected to participate as one of six partner sites with its concept "Precision in Mental Health (PriMe): Understanding, predicting, and preventing chronicity." PriMe bundles interdisciplinary research from the Ludwig-Maximilians-University (LMU), Technical University of Munich (TUM), University of Augsburg (UniA), Helmholtz Center Munich (HMGU), and Max Planck Institute of Psychiatry (MPIP) and has a focus on schizophrenia (SZ), bipolar disorder (BPD), and major depressive disorder (MDD). PriMe takes a longitudinal perspective on these three disorders from the at-risk stage to the first-episode, relapsing, and chronic stages. These disorders pose a major health burden because in up to 50% of patients they cause untreatable residual symptoms, which lead to early social and vocational disability, comorbidities, and excess mortality. PriMe aims at reducing mortality on different levels, e.g., reducing death by psychiatric and somatic comorbidities, and will approach this goal by addressing interdisciplinary and cross-sector approaches across the lifespan. PriMe aims to add a precision medicine framework to the DZPG that will propel deeper understanding, more accurate prediction, and personalized prevention to prevent disease chronicity and mortality across mental illnesses. This framework is structured along the translational chain and will be used by PriMe to innovate the preventive and therapeutic management of SZ, BPD, and MDD from rural to urban areas and from patients in early disease stages to patients with long-term disease courses. Research will build on platforms that include one on model systems, one on the identification and validation of predictive markers, one on the development of novel multimodal treatments, one on the regulation and strengthening of the uptake and dissemination of personalized treatments, and finally one on testing of the clinical effectiveness, utility, and scalability of such personalized treatments. In accordance with the translational chain, PriMe's expertise includes the ability to integrate understanding of bio-behavioral processes based on innovative models, to translate this knowledge into clinical practice and to promote user participation in mental health research and care.

Keywords: bipolar disorder; comorbidities; depression; mortality; precision medicine; schizophrenia.

FIGURE 1

Map of the PRiME’s catchment area. PSY Teaching Hospitals LMU: 1. Klinikum Ingolstadt, 2. Hospital Fürstenfeldbruck, 3. Hospital München Ost, 4. Hospital Wasserburg, 5. Hospital Rosenheim, 6. Day Clinic Freilassing, 7. Hospital Memmingen. PSY Teaching Hospitals TUM: 1. Hospital Pfaffenhofen, 2. Hospital Landshut-Achdorf, 3. Hospital Freising, 4. Hospital Schwabing, 5. Hospital Bogenhausen, 6. Hospital Agatharied, 7. Hospital Garmisch-Partenkirchen. BKS Swabia network UniA: 1. Outpatient unit and day clinic Aichach, 2. Hospital Kaufbeuren, 3. Hospital Memmingen (allocated to two institutions), 4. Hospital Kempten, Day Clinic Lindau, 6. Hospital Obergünzburg, 7. Hospital Günzburg.

FIGURE 2

Concept figure illustrating the dynamics of mental disorders from a life-span perspective: (A) Incidence increases between adolescence and adulthood and toward old age. (B) Disease phenotypes evolve from non-specific to specific/severe manifestations. Arrows from panels (B) to (C) indicate how specificity/severity of phenotypes relates to disease strata. Heterogeneity increases as progressive and non-progressive trajectories, ranging from highly disabling phenotypes to minor impairments, mix at the population level. (C) Increasing functional impairment with disease progression from unspecific, at-risk to established episodic or chronic disease strata. At the bottom of the figure the positioning of different German Centres of Health covering mental healthcare-relevant topics across the lifespan are depicted. BPD, bipolar disorder; CHR, clinical high risk; DZD, German Center for Diabetes Research; DZHK, German Center for Cardiovascular Research; DZKJ, German Center for Child and Adolescent Health; DZPG, German Center for Mental Health; MDD, major depressive disorder; and SZ, schizophrenia.

FIGURE 3

Concept figure representing the translational chain from understanding over development of predictive tools to their translation into clinical practice through stratified clinical trials (A–D). The upper part depicts the envisaged bench-to-bedside sequence, while the lower part lists relevant research activities at each translational step that are being pursued by PriMe. iPSC, induced pluripotent stem cells; ML, machine learning; MRI, magnetic resonance imaging; NLP, neurolinguistic programming; NTBS, non-invasive transcranial brain stimulation; and PriMe, Precision in Mental Health.

FIGURE 4

Use cases exemplifying the potential of biomarkers and risk prediction models for clinical translation: (A) Development and clinical evaluation of spironolactone as treatment for cognitive deficits in patients with schizophrenia (42). (B) Development and validation of an individualized structural magnetic resonance imaging-based rTMS response predictor for the targeted treatment of negative symptoms in schizophrenia (43). (C) Identification of a molecular mechanism of difficult-to-treat depression leading to the development of a small-molecule antagonist of FKBP5-induced disinhibition in rodents, with planned clinical translation (44, 45). IIT, investigator-initiated trial.

FIGURE 5

Mapping between PRiME’s translational chain and envisaged research platform in the new German Centre for Mental Health (DZPG). These platforms will be generic and thus accessible by all sites of the DZPG to facilitate the rapid translation of knowledge into therapies for all mental disorders. Boxes represent topics where PriMe could benefit from the expertise of other potential DZPG sites. AI, artificial intelligence; DZPG, German Center for Mental Health; EBM, evidence-based medicine; and ML, machine learning.