Klinik für Psychiatrie und Psychotherapie

Research focus

Our group investigates the pathogenesis, treatment, and prevention of stress-associated and emotional mental disorders, particularly anxiety, mood and obsessive-compulsive disorders, by combining clinical and neurobiological, particularly (epi)genetic, research in a multi-level approach.

State and trait markers of mental disorders and their intermediate phenotypes
In accordance with the vulnerability-stress model of mental disorders, a multitude of interacting factors play a crucial role in their pathogenesis and maintenance. Gaining a better understanding of the state and trait markers associated with mental disorders, their clinical subtypes and symptom dimensions is of utmost importance for advancing diagnostic, prognostic and therapeutic options, which are therefore investigated by our group.

Treatment outcome prediction and personalized treatment of mental disorders
While highly effective psychotherapeutic as well as pharmacological treatment options are available, not all patients respond to the first-line treatments in a clinically meaningful way. A precise prediction of individual treatment response offers the chance to optimize individual treatment selection early on. Our research focuses on synthesizing clinical, psychological, neurobiological and environmental information in an effort to determine and investigate personalized treatment options for the individual patient.

Mechanisms of action underlying successful behavioral change through psychotherapy
Cognitive behavioral therapy (CBT) is considered the gold standard for the psychotherapeutic treatment of many mental disorders. However, the precise mechanisms of action mediating psychotherapeutic outcome are still poorly understood. Therefore, employing a multi-level approach, our aim is to identify correlates and putative mechanisms of clinical change occurring over the course of psychotherapy.

Our laboratories

Methodologically, the group combines molecular biological and clinical research methods.

On a neurobiological level, the group runs a Molecular Biological Laboratory fully equipped to perform versatile and rapid genotyping, DNA methylation analyses (pyrosequencing, direct sequencing) and analysis of histone modification such as acetylation and methylation (ChIP, qPCR).

Clinically, the group maintains a dedicated research outpatient clinic for anxiety disorders and operates a state-of-the-art Virtual Reality Laboratory. One main scientific focus is the implementation and development of psychotherapeutic interventions in VR in order to establish innovative, VR-based treatment approaches accompanied by psychoneurobiological research.

Research projects

• Targetable epigenetic, physiological and neuroimaging risk markers of anxiety sensitivity - A developmental, cross-disorder prevention study of separation anxiety and panic disorder (SFBTRR-58, project C02)
• Gene-environment interactions, neural circuits and generalization in dimensional endophenotypes of anxiety in adults and children: Development and reversibility (SFBTRR-58, project Z02)
• (Epi)genetic effects related to extinction learning and outcome (PROTECT-AD, project P5)
• Therapyepigenetics of Obsessive-Compulsive Disorder (EQUIP Medical Scientist Funding, Faculty of Medicine, University of Freiburg)
• Epigenetic risk markers as well as predictors and mechanisms of psychotherapy in acrophobia: spotlighting the BDNF system (DFG)

Selected publications

Reviews

• Schiele MA, Domschke K (2018) Epigenetics at the crossroads between genes, environment and resilience in anxiety disorders. Genes Brain Behav 17:e12423.
• Schiele MA, Bandelow B, Baldwin DS, Pini S, Domschke K (2020) A neurobiological framework of separation anxiety and related phenotypes. Eur Neuropsychopharmacol 33:45-57.
• Schiele MA, Gottschalk MG, Domschke K (2020) The applied implications of epigenetics in anxiety, affective and stress-related disorders - a review and synthesis on psychosocial stress, psychotherapy and prevention. Clin Psychol Rev 77:101830.
• Ell MA, Schiele MA, Iovino N, Domschke K (2023) Epigenetics of fear, anxiety and stress - focus on histone modifications. Curr Neuropharmacol [in Druck]

Original articles

• Domschke K, Gajewska A, Winter B, Herrmann MJ, Warrings B, Mühlberger A, Wosnitza K, Glotzbach E, Conzelmann A, Dlugos A, Fobker M, Jacob C, Arolt V, Reif A, Pauli P, Zwanzger P, Deckert J (2012) ADORA2A gene variation, caffeine and emotional processing – a multi-level interaction on startle reflex, Neuropsychopharmacology 37:759-769.
• Domschke K, Reif A, Weber H, Richter J, Hohoff C, Ohrmann P, Pedersen A, Bauer J, Suslow T, Kugel H, Heindel W, Baumann C, Klauke B, Jacob C, Maier W, Fritze J, Bandelow B, Krakowitzky P, Rothermundt M, Erhardt A, Binder EB, Holsboer F, Gerlach AL, Kircher T, Lang T, Alpers GW, Ströhle A, Fehm L, Gloster AT, Wittchen HU, Arolt V, Pauli P, Hamm A, Deckert J (2011) Neuropeptide S receptor gene – converging evidence for a role in panic disorder. Mol Psychiatry 16:938-948.
• Domschke K, Tidow N, Kuithan H, Schwarte K, Klauke B, Ambrée O, Reif A, Schmidt H, Arolt V, Kersting A, Zwanzger P, Deckert J (2012b) Monoamine oxidase A gene DNA hypomethylation - a risk factor for panic disorder? Int J Neuropsychopharmacol 15:1217-1228.
• Schiele MA, Herzog K, Kollert L, Schartner C, Leehr EJ, Böhnlein J, Repple J, Rosenkranz K, Lonsdorf TB, Dannlowski U, Zwanzger P, Reif A, Pauli P, Deckert J, Domschke K (2020) Extending the vulnerability-stress model of mental disorders: three-dimensional NPSR1 × environment × coping interaction study in anxiety. Br J Psychiatry 217:645-650.
• Schiele MA, Thiel C, Deckert J, Zaudig M, Berberich G, Domschke K (2020) Monoamine oxidase A hypomethylation in obsessive-compulsive disorder - reversibility by successful psychotherapy? Int J Neuropsychopharmacol 23:319-323.
• Schiele MA, Reif A, Lin J, Alpers GW, Andersson E, Andersson G, Arolt V, Bergström J, Carlbring P, Eley TC, Esquivel G, Furmark T, Gerlach AL, Hamm A, Helbig-Lang S, Hudson JL, Lang T, Lester KJ, Lindefors N, Lonsdorf TB, Pauli P, Richter J, Rief W, Roberts S, Rück C, Schruers KRJ, Thiel C, Wittchen H-U, Domschke K, Weber H, Lueken U (2021) Therapygenetic effects of 5-HTTLPR on cognitive-behavioral therapy in anxiety disorders: A meta-analysis. Eur Neuropsychopharmacol 44:105-120.
• Schiele MA, Thiel C, Kollert L, Fürst L, Putschin L, Kehle R, Hauke W, Mahr M, Reinhold E, Gottschalk MG, Heinrichs M, Zaudig M, Berberich G, Domschke K (2021) Oxytocin receptor gene DNA methylation – a biomarker of treatment response in obsessive-compulsive disorder? Psychother Psychosom 90:57-63.
• Schiele MA, Ziegler C, Kollert L, Katzorke A, Schartner C, Busch Y, Gromer D, Reif A, Pauli P, Deckert J, Herrmann MJ, Domschke K (2018). Plasticity of functional MAOA gene methylation in acrophobia. Int J Neuropsychopharmacol 21:822-827.
• Schiele MA, Zwanzger P, Schwarte K, Arolt V, Baune BT, Domschke K (2021) Serotonin transporter gene promoter hypomethylation as a predictor of antidepressant treatment response in major depression – a replication study. Int J Neuropsychopharmacology 24:191-199.
• Ziegler C, Dannlowski U, Braeuer D, Stevens S, Laeger I, Wittmann H, Tidow N, Mahr M, Kugel H, Heindel W, Dobel C, Hurlemann R, Reif A, Lesch KP, Arolt V, Gerlach A, Hoyer J, Deckert J, Zwanzger P, Domschke K (2015) Oxytocin receptor (OXTR) gene methylation – converging evidence for a role in social anxiety, Neuropsychopharmacology 40:1528-1538.
• Ziegler C, Grundner-Culemann F, Schiele MA, Schlosser P, Kollert L, Mahr M, Gajewska A, Lesch KP, Deckert J, Köttgen A, Domschke K (2019). The DNA methylome in panic disorder: a case-control and longitudinal psychotherapy-epigenetic study. Transl Psychiatry 9:314.
• Ziegler C, Richter J, Mahr M, Gajewska A, Schiele MA, Gehrmann A, Schmidt B, Lesch KP, Lang T, Helbig-Lang S, Pauli P, Kircher T, Reif A, Rief W, Vossbeck-Elsebusch AN, Arolt V, Wittchen HU, Hamm AO, Deckert J, Domschke K (2016) MAOA gene hypomethylation in panic disorder-reversibility of an epigenetic risk pattern by psychotherapy, Transl Psychiatry 6:e773.

PubMed

Funding

• Deutsche Forschungsgemeinschaft (DFG)
• Bundesministerium für Bildung und Forschung (BMBF), PROTECT-AD
• European Union (EU), EUSARNAD, FP7-PEOPLE-2010-IRSES
• Interdisziplinäres Zentrum für Klinische Forschung (IZKF), Würzburg
• EQUIP Medical Scientist Funding, Medical Faculty, University of Freiburg
• Forschungskommission der Medizinischen Fakultät, Universität Freiburg

Cooperations and Networks

• DFG Sonderforschungsbereich SFB/Transregio 58 "Furcht, Angst, Angsterkrankungen"
• BMBF Forschungsverbund PROTECT-AD
• Gesellschaft für Angstforschung (GAF)
• Anxiety Disorders Research Network (ADRN), European College of Neuropsychopharmacology (ECNP)
• Obsessive Compulsive and Related Disorders Network (OCRN), European College of Neuropsychopharmacology (ECNP)
• Prevention of Mental Disorders and Mental Health Promotion Network, European College of Neuropsychopharmacology (ECNP)
• Thematic Working Group on Resilience, European College of Neuropsychopharmacology (ECNP)

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