Trajectories of affective disorders: neurobiological mechanisms during symptom change.

Journal: Der Nervenarzt
Published Date: Nov 20, 2025

Abstract

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).

Authors

  • Ulrich W Ebner-Priemer
    Mental mHealth Lab, Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Hertzstr. 16, Building 06.31, Karlsruhe, 76187, Germany, 49 721 608 47543.
  • Judith Alferink
    Department of Psychiatry, University of Muenster, Muenster, Germany3Cells-in-Motion Cluster of Excellence, University of Muenster, Muenster, Germany.
  • Michael Bauer
    Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus Medical Faculty, Technische Universität Dresden, Dresden, Germany.
  • Udo Dannlowski
    Department of Psychiatry and Psychotherapy, University of Münster, Germany.
  • Irina Falkenberg
    Department of Psychiatry and Psychotherapy, Philipps-Universität Marburg, Marburg, Germany.
  • Andreas J Forstner
    Institute for Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
  • Tim Hahn
  • Markus Junghöfer
    Institute for Biomagnetism and Biosignalanalysis, University of Münster, Germany.
  • Tilo Kircher
    Department of Psychiatry, University of Marburg, Marburg, Germany.
  • Luisa Klotz
    Department of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany.
  • Julia Martini
    Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany.
  • Eva Mennigen
    Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany.
  • Igor Nenadić
    Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany; Department of Psychiatry and Psychotherapy, Philipps University Marburg & Marburg University Hospital UKGM, Marburg, Germany. Electronic address: [email protected].
  • Carmine Pariante
    Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany.
  • Andrea Pfennig
    Department of Psychiatry and Psychotherapy, Carl Gustav Carus University Hospital, Technical University Dresden, Dresden, Germany.
  • Michael Ziller
    Department of Psychiatry, University of Münster, Münster, Germany.
  • Susanne Meinert
    Institute for Translational Psychiatry, University of Münster, Germany; Institute for Translational Neuroscience, University of Münster, Germany.

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