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What to target? Interventions to modulate key mechanisms underlying the trajectories of affective disorders in the

Elisabeth J Leehr¹, Joachim Groß², Stefan G Hofmann³

¹Institute for Translational Psychiatry, University of Münster, Albert-Schweitzer-Campus 1, Building A9, 48149, Münster, Germany. leehr@uni-muenster.de.

|November 27, 2025

Abstract

Background:

Affective disorders are associated with an enormous disease burden, necessitating research on the mechanisms of effective treatments.

Objectives:

This article introduces the intervention projects of the transregional Collaborative Research Center 393 (CRC/TRR 393). By employing targeted interventions, we aim to induce modifiability in the key mechanisms underlying the trajectories of affective disorders studied in CRC/TRR 393: emotion regulation, expectation, social cognition, and (circadian) cognitive-behavioral rhythms.

Materials And Methods:

The longitudinal design of the CRC/TRR 393 study will examine four interventions targeting specific mechanisms in subgroups of the German Mental Health Cohort (GEMCO). GEMCO includes patients with a current or lifetime diagnosis of major depressive disorder (MDD), bipolar disorder (BD), and healthy control (HC) participants. Multilevel measurements of these targeted mechanisms will allow us to investigate their fine-grained modifiability and their effects on disease trajectories.

Results:

The results will provide insights into how these mechanisms can be modified. Together with the CRC/TRR 393 mechanisms projects, we will examine the effects of key cognitive-emotional mechanisms on disease trajectories.

Conclusion:

For the first time, the modifiability of four key mechanisms underlying the trajectories of affective disorders will be investigated both cross-sectionally and longitudinally.

Keywords:

Affective disorders, emotion regulation Circadian rhythm Empathy Expectation violation Mood disorders

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