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Effective treatment of affective disorders (AD) requires a deep understanding of the underlying neurobiological mechanisms. However, in machine-learning-based analyses, cross-sectional studies have failed to identify robust individual-level biomarkers. Research Domain A of CRC/TRR393 addresses this gap by implementing longitudinal, multimodal studies using real-time mobile assessments. Central to this effort is the identification of "inflection signals"-clinically meaningful symptom changes marking transitions from euthymia to depressive or (hypo)manic episodes. These critical windows are captured through digital phenotyping and ecological momentary assessments and followed up by in-depth neurobiological profiling. Six projects examine the dynamic interplay of behavioral, cognitive-emotional, molecular, immune, and neural mechanisms during these transitions. Project A01 validates early-warning models using digital phenotypes and machine learning. Project A02 maps structural and functional brain changes in relation to disease course and risk factors. Project A03 investigates the role of microglial immune activation in recurrent depression. Project A04 investigates neurobiological alterations after inflection signals using intensive, multimodal data acquisition conducted both in laboratory settings and in the participants' personal environments. Project A05 adds molecular and immunological profiling and integrates findings from human and animal data. Project A06 studies trajectories from bipolar at-risk states to full-blown illness. Together, these projects form the empirical foundation for mechanism-based interventions (Domain C) and theoretical modeling of symptom trajectories (Domain B).

Background: Memory clinics in Germany are facing major challenges due to increasing numbers of patients and the first available disease-modifying treatments for Alzheimer's disease. Capacities for counselling, biomarker-based diagnostics, drug administration and follow-up examinations must be achieved, which creates the need for modified workflows. Value-based healthcare (VBHC) aims at optimizing the value for patients (outcome in relation to costs) and can serve as a framework for a patient-oriented increase in efficacy.

Objective: This project applied approaches of VBHC to analyze and improve the diagnostic processes in our memory clinic in order to achieve a better value for patients and care partners with a more efficient use of existing resources.

Methods: In a first survey among memory clinic patients and relatives the essential aspects in relation to VBHC were collated and based on the results the existing workflow processes were modified. These modifications were evaluated by a second survey and analysis particularly of process-oriented aspects.

Results: The first survey revealed a general satisfaction with the presentation in the memory clinic. The main point of criticism was the duration of the diagnostic process. After the modification the duration and extent of the diagnostics could be reduced. The second evaluation showed improved patient and care partner satisfaction. The respondents considered the modified trajectories to be better and resources were conserved.

Conclusion: In our memory clinic an improvement in the sense of VBHC could be achieved through an increased satisfaction with the treatment (outcome) and reduced personnel binding times (costs). This approach can serve as a model for other memory clinics for the development of a more efficient and patient-centered care.

Background: Antipsychotic medications (AP) are a central component in the treatment of psychotic disorders. The question arises how to balance long-term pharmacological treatment with the possibility of reduction or discontinuation (R&D). The German S3 guidelines for schizophrenia provide a general framework for R&D but concrete recommendations for practical implementation are still lacking.

Objective: This qualitative study aims to explore the attitudes, challenges and reduction strategies of outpatient psychiatrists in Berlin and Brandenburg regarding the R&D of antipsychotics, in order to draw conclusions about the current state of care and potential gaps in service provision.

Material and methods: In this study 10 semi-structured interviews with outpatient psychiatrists and one focus group with psychiatrists were conducted. The data were analyzed using thematic analysis.

Results: The participating psychiatrists predominantly favored an individualized and gradual approach to reducing antipsychotics. While some reported feeling confident and drew on their own clinical experience, others expressed considerable uncertainty and concern regarding the discontinuation process. This uncertainty was partly attributed to a perceived lack of specific guidance for practical implementation, which led to a sense of individual responsibility. Structural barriers, such as limited psychosocial support services and the lack of availability of finely graduated dosage forms, further hinder the implementation of effective reduction strategies.

Discussion: A clearer position in clinical guidelines, including more specific recommendations on R&D, could help reduce uncertainty among psychiatrists. Furthermore, enhanced psychosocial and psychotherapeutic support services would be necessary to enable a safe R&D process in outpatient settings.

Background: Although affective disorders are a major driver of disability worldwide, there is a lack of understanding of the mechanisms and modulating factors involved in the long-term disease trajectories.

Objectives: Our goal is to determine key cognitive-emotional mechanisms in the domains of emotion regulation, expectation, social cognition, and cognitive-behavioral rhythms and their neurobiological correlates in the progression of affective disorders, including recurrences and remissions, chronicity, and functional decline.

Materials and methods: In CRC/TRR 393, we will pursue a multi-level investigation of these four domains. Within the German Mental Health Cohort (GEMCO), these mechanisms and their influence on disease trajectories will be investigated longitudinally. Parallelized human and animal projects will enable an in-depth characterization of their neurobiological correlates.

Results: By leveraging recent advancement in the modeling of complex, dynamic systems and machine learning techniques, we will be able to integrate human and animal data on the key cognitive-emotional mechanisms and their interplay with stressors and other modifying factors across disease trajectories.

Conclusion: Gaining a deeper understanding of the cognitive-emotional mechanisms in the progression of affective disorders will help to predict symptom changes and course of illness as well as to identify key targets of intervention.

Background: People with severe mental disorders often need multiprofessional treatment and support, even between acute phases of illness. During the integration support they repeatedly switch between inpatient acute care and outpatient community psychiatric care.

Objective: What is integration support? What tasks in the care of severely mentally ill people are fulfilled by integration assistance? How can cooperation between acute psychiatry and integration support be successful?

Material and method: Selective literature search.

Results: The integration support according to the Social Security Code IX (SGB IX) serves to support social participation. This need is often present in the group of severely mentally ill people. Integration support services can be used flexibly and needs oriented. The cross-sectoral, person-centered treatment of this patient group requires close coordination between clinics, outpatient therapists and integration support, for example by case conferences and case management.

Conclusion: Clinics, outpatient practitioners and providers of integration support should closely cooperate with each other to provide social inclusion for severe mentally ill patients.

This article describes the development and criticism of community psychiatry in Germany since the 1975 Inquiry Commission on Psychiatry as well as its precursors and reference points. While the inquiry called for fundamental reforms such as the establishment of community-based care structures, the concrete content and structural guidelines remained vague. This lack of clarity meant that community psychiatry was characterized less by central reforms than by a large number of regional model projects. With a view to the historical context, this project orientation is interpreted as an expression of a shift in focus since the 1980s towards self-help, civil society actors and the flexibilization of the social state. Although projectification has led to diversification and professionalization, it has also resulted in uncertainty, lack of sustainability and fragmentation of care. Community psychiatry is thus seen as a mirror of social and political change.

Background: Young people in mental health crises have severely limited access to clinical care and show the lowest adherence to conventional clinical services. Low-threshold and integrated services (integrated youth mental health services, IYMHS) are recommended to overcome these barriers and provide early detection, early intervention and psychosocial care appropriate for young people.

Objective: The aim is to provide an overview of low-threshold IYMHS globally and in Germany and to report on international experiences with these services and evidence of their effectiveness.

Methods: The narrative review is based on research conducted in PubMed, including the use of published reviews.

Results: International developments show that IYMHS have become established as innovative models of care for young people in mental health crises. Australia is seen as a pioneer with its nationwide network of headspace centers. In Germany, soulspace is the first model project and another, ancora, is in the pipeline. Evaluations to date show that many young people who would not otherwise have sought help use these integrated services and predominantly experience symptomatic and functional improvements.

Conclusion: International experiences to date and pilot projects in Germany have demonstrated the potential of IYMHS to provide low-threshold support at an early disease stage to young people with first symptoms of mental health. For Germany, expanding an integrated, cross-sectoral care structure is recommended through pooling resources from statutory health insurances and public funding.