Research

The research group Predictive Psychiatry investigates neurobiological and clinical markers for predicting disease trajectories and treatment response in mental disorders. Using multimodal imaging, biomarkers, and cognitive testing, we develop approaches for personalized and evidence-based psychiatry.

Our research group is interested in identifying clinical and neurobiological markers that have predictive value in regard to disease trajectory and treatment response in mental disorders. We employ multimodal neuroimaging, with a focus on structural and functional connectomics, blood-based biomarkers like genetic and metabolic markers as well as clinical characterization and cognitive testing to elucidate mechanisms behind disease trajectories and to identify clusters of patients that are suitable for specific antidepressive treatments.

•  Treatment Response Prediction

•  Chronic and Difficult-to-Treat Depression

•  Neuromodulation of Brain Networks

•  Cognitive dysfunction in Mental Disorders

• Magnet Resonance Imaging (MRI)

• Transcranial Magnetic Stimulation (TMS)  

• structural and functional Connectomics 

• Modeling of psychological and symptom networks

• Network Control Theory

• Normative Modeling

FRAME-DT Studie

In this project, we follow patients diagnosed with a depressive syndrome who receive either medication treatment or treatment via transcranial magnetic stimulation (TMS) or electroconvulsive therapy (ECT) during their stay at the clinic. We characterize these patients as precisely as possible - psychologically and biologically - before, during, and after treatment in order to identify predictors and mechanisms of treatment success. To achieve this, we conduct detailed clinical interviews, questionnaires, neuropsychological assessments, brain MRI measurements (with a focus on brain connectivity), and blood analyses.

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Duration: since 2023

Dynamic Changes under TMS Treatment in Depression (DYNAMIC-TMS)

As part of the DYNAMIC consortium we explore how the brain, behavior, and mental well-being are connected. Mental illnesses are usually diagnosed using fixed categories based on a certain number of symptoms over time. However, this approach often cannot fully explain how symptoms develop, influence each other, or change over time. In DYNAMIC we view mental health as a network of interacting psychological and biological processes. 
 By studying this network, we aim to gain a deeper understanding of the dynamic mechanisms underlying mental disorders. In particular, we investigate how transcranial magnetic stimulation (TMS) influences symptom networks in depression to better understand which patients are most likely to benefit from this treatment.

Participants follow a comprehensive assessment, including brain imaging (MRI, EEG), computer and memory tasks, clinical interviews, questionnaires, and smartphone-based daily surveys.

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Cooperations:

• Fachbereich Psychologie der Goethe-Universität Frankfurt
• Fachbereich Informatik und Mathematik der Goethe-Universität Frankfurt
• Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters Frankfurt
• Klinik für Psychiatrie und Psychotherapie Marburg
• Fachbereich Psychologie der Philipps-Universität Marburg
• Klinische Kinder- und Jugendpsychologie Marburg
• Klinik für Kinder- und Jugendpsychiatrie Marburg
• Klinik für Psychiatrie und Psychotherapie Gießen
• Fachbereich Psychologie der Justus-Liebig-Universität Gießen
• Verhaltenstherapeutische Ambulanz für Kinder und Jugendliche Gießen
• Fachbereich Informatik der Technischen Universität Darmstadt
• DIPF | Leibniz-Institut für Bildungsforschung und Bildungsinformation
• Ernst Strüngmann Institut für Neurowissenschaften

Duration: 2024 - 2030

TMS in Substance Use Disorder (TMS-SUD)

In this study, we are investigating the effects of frontopolar transcranial magnetic stimulation (TMS) on psychological, physiological, and neurobiological correlates of alcohol craving in patients with alcohol dependence. The aim is to gain a better understanding of the neurobiological mechanisms underlying craving and to evaluate new, innovative treatment approaches for relapse prevention. To this end, we combine accelerated, neuronavigated theta-burst stimulation (cTBS) with virtual-reality-based cue exposure, as well as structural and functional magnetic resonance imaging (MRI). Using these multimodal data, we also aim to predict individual treatment response, which could help tailor interventions to each patient’s specific neurobiological and behavioral profile.

Duration: 2024 - 2028

MINDSYNC

In this study, we are investigating how cognitive difficulties interact with depressive symptoms in young adults with depression. The aim is to better understand these connections and to identify which brain characteristics predict successful treatment outcomes. To this end, we combine daily smartphone-based assessments of mood and cognitive function with a two-part cognitive training program consisting of app-based exercises and regular group sessions, as well as structural and functional magnetic resonance imaging. Using these multimodal data, we aim to predict individual treatment response, which could help tailor interventions to each person's specific symptom patterns and neurobiological profile.

Laufzeit: 2026

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Group Leader:

Univ.-Prof. Dr. med. Jonathan Repple
E-Mail: repple@em.uni-frankfurt.de

Team Members:

• Dr. Marius Gruber - PostDoc
• Paula Rehm - PhD
• Henry Staub - PhD
• Franka Timm - PhD
• Lea Krätzig - PhD
• Sonja Langenstein - Research Associate
• Alicia Mohn – Research Associate
• Stefanie Fischer - Clinician Scientist
• Lea Anthes - Research Associate
• Delia Schepers - Research Associate (PhD) 
• Mohsen Partodezfouli - Postdoctoral Researcher
• Kurt Noack - Junior Clinician Scientist
• Leon Scholz - Research Associate
• Ana-Christina Panzer – Student Assistant
• Caroline Geskes – Student Assistant
• Delia Schepers – Student Assistant
• Elise Ju-Hee Kim – Student Assistant
• Emily Sürken – Student Assistant
• Hannah Schneider – Student Assistant
• Isabel Reukauf – Student Assistant
• Joohyun Kang – Student Assistant
• Luca Müller – Student Assistant

Pictured (top to bottom, left to right): Univ.-Prof. Dr. med. Jonathan Repple, Dr. Kira F. Ahrens, Dr. Marius Gruber,  Franka Timm, Paula Rehm, Henry Staub, René Bürgel, Delia Schepers, Lea Krätzig, Caroline Geskes, Stefanie Fischer, Elise JuHee Kim, Max Nieswandt

• Stefanie Fischer: 2026 Mini-Grant LOEWE Research Center DYNAMIC for early-career researcher: “METADYN - Metabolic Predictors of Symptom Network Dynamics in Depression”
• Henry Staub: 2026 Mini-Grant LOEWE Research Center DYNAMIC for early-career researcher: “From brain stimulation to daily life: smartphone data may predict treatment response in depression”
• Henry Staub: 2025 ECNP Excellence Award - Validating antidepressant TMS targets using network control theory
• Kira Ahrens: 2025 Stifterpreis Sozialpsychiatrie Frankfurt
• Marius Gruber: 2024 Hans-Heimann-Promotionspreis der Deutschen Gesellschaft für Psychiatrie, Psychotherapie, Psychosomatik und Nervenheilkunde (DGPPN)

• “Structural Connectome Alterations in Atypical Depression” – Gina Rösch

• “Structural Connectome Alterations in Schizophrenia with and without Hallucinations” – Isabel Reukauf

• “Symptom-specific connectome alterations in MDD” – Jasmin Müller

• “Structural and Functional Connectome Alterations in Chronic Depression” – René Bügel

• “Vulnerability Stress Model in Depression: Interplay of Genetic Liability, Perceived Stress, and Connectome Alterations” – Julia Tomlin

• “Connectome-based differential diagnosis between MDD and BD” – Ana Panzer

• “Mapping the Molecular Foundations of Neural Networks in Bipolar Disorder” – Stefanie Fischer

• “Folate Serum Levels and Symptoms of Insomnia in Depression” – Rosa Maclean

• “Changes in metabolite concentrations during antidepressive treatments in in-patients” – Fenja Denker

• “The interplay of demographic factors with verbal fluency deficits in depression” – Maryam Wardah

• “DigiProfile - Einführung und Analyse digitalisierter Fragebögen in der psychiatrischen Tagesklinik mit Fokus auf kindliche Traumatisierungen und Therapieansprechen”- Hannah Schneider

• “Validierung des deutschsprachigen DSM-5 Cross-Cutting Fragebogens (CCSM) in einer klinischen, transdiagnostischen Stichprobe” - Elise Kim

• “Dysfunctional Metabolism as a Mechanism of Structural Connectome Alterations in Depression” – Delia Schepers

Full list: Google scholar. Selected publications:

1. van den Heuvel MP, Libedinsky I, Quiroz Monnens S, Repple J, Sommer I, Cocchi L. Investigating the methodological foundation of Lesion Network Mapping. Nature Neuroscience. Nat Neurosci. 2026 Jan 15. doi: 10.1038/s41593-025-02196-7. [IF: 20.0]

2. Gruber M, Schulte J, Mauritz M, Ahrens KF, Rehm P, von Werthern N, Staub H, Fischer S, Timm F, Libedinsky I, Grumbach P, Bonnekoh LM, Goltermann J, Winter NR, Thiel K, Winter A, Borgers T, Klug M, Meinert H, Hubbert J, Krieger J, Jurischka C, Thomas-Odenthal F, Usemann P, Teutenberg L, Pawlitzki M, Förster K, Sindermann L, Böhnlein J, Meinert S, Grotegerd D, Stein F, Straube B, Alexander N, Jamalabadi H, Jansen A, Nenadić I, Opel N, Hahn T, Bauer J, van den Heuvel MP, Reif A, Kircher T, Leehr EJ, Dannlowski U, Repple J. Network-Based Analysis of Differential White Matter Connectivity in Major Depressive Disorder with and without Comorbid Anxiety. Neuropsychopharmacology. 2026 Jan 12. doi: 10.1038/s41386-025-02312-y [IF: 7.1]

3. Bonnekoh LM*, Gruber M*, Thams C, Flinkenflügel K, Meinert S, Goltermann J, Grotegerd D, Hubbert J, Krieger J, Jurischka C, Fellmeth RH, Winter NR, Hahn T, Leehr EJ, Opel N, Pawlitzki M, Rehm P, V Werthern N, Edwin Thanarajah S, Fischer S, Ahrens KF, Reif A, Stein F, Thomas-Odenthal F, Usemann P, Teutenberg L, Staub H, Meinert H, Alexander N, Jamalabadi H, Jansen A, van den Heuvel MP, Nenadić I, Straube B, Romer G, Kircher T, Dannlowski U*, Repple J*. Structural connectomic signatures of childhood maltreatment across affective and psychotic disorders. EurNeuropsychopharmacol. 2025 Nov;100:42-52. doi: 10.1016/j.euroneuro.2025.09.009. Epub 2025 Oct 13. PMID: 41086650. [IF: 5.9]

4. Repple J, Bayas M, Möser C, Kobayashi NF, Reif A. Current Evidence for the Role of Rapid-Acting Antidepressants in Bipolar Depression: A Perspective and Plan for Action. Biol Psychiatry. 2025 Aug 15;98(4):333-342. doi: 10.1016/j.biopsych.2025.02.903. Epub 2025 Mar 8. PMID: 40064389. [IF: 9.0]

5. Repple J*, Gruber M*, Mauritz M, de Lange S, Winter N, Opel N, Goltermann J, Meinert S, Grotegerd D, Leehr E, Enneking V, Borgers T, Klug M, Lemke H, Waltemate L, Thiel K, Winter A, Breuer F, Grumbach P, Hofmann H, Stein F, Brosch K, Ringwald K, Pfarr J, Thomas-Odenthal F, Meller T, Jansen A, Nenadic I, Redlich R, Bauer J, Kircher T, Hahn T, van den Heuvel M*, Dannlowski U *(2023): Shared and specific patterns of structural brain connectivity across affective and psychotic disorders. Biological Psychiatry 2023 Jan 15;93(2):178-186. doi: 10.1016/j.biopsych.2022.05.031.[IF: 13.4]