Klinik für Psychiatrie und Psychotherapie

Research focus

• Genetics and epigenetics of anxiety disorders and depression
  Anxiety disorders and depression are among the most frequent mental disorders with lifetime prevalence rates of about 20%. Twin studies indicate a considerable heritability (40-87%) of these disorders with contributions from several different genes, which interact with each other as well as with environmental factors in a complex-genetic model. Additionally, epigenetic mechanisms such as DNA methylation have become a central focus in psychiatric research as a dynamic link between genetic make-up and environmental stress shaping the overall disease risk. Our aims are to identify genetic and epigenetic factors as well as their interplay with environmental influences contributing to the development of anxiety disorders and depression.
• (Epi)genetics of intermediate phenotypes of anxiety disorders and depression
  The influence of genetic factors on anxiety and depressive disorders can be further specified by the consideration of so-called ‘intermediate phenotypes’. Intermediate phenotypes comprise heritable neurobiological or neuropsychological traits (e.g. anxiety sensitivity, neural activation patterns, startle reflex) that are linked to the disorder of interest, and, unlike the overall categorical disease phenotype, are dimensional, closely defined constructs and are therefore considered to be closer to the underlying genotype. Their investigation constitutes another central focus of our group.
• Therapy(epi)genetics of anxiety disorders and depression
  In the treatment of anxiety disorders and depression, efficacious pharmacological (e.g. SSRIs, SNRIs) and psychotherapeutic (e.g. CBT) options are available. However, treatment-resistance is a common problem in clinical practice, with about 30% of patients responding insufficiently to the initial treatment. Our workgroup aims to identify predictive genetic and epigenetic markers of favorable therapy response, as well as to elucidate epigenetic mechanisms of change in the course of treatment towards the development of a “precision medicine” approach corresponding to a patient’s individual risk factor constellation.
• Prediction and prevention of anxiety disorders and depression
  Anxiety and depressive disorders present with high chronicity and confer a substantial socioeconomic burden. They are highly comorbid, both with each other as well as with other mental disorders. Anxiety disorders can already manifest early in childhood and are characterized by high progression towards other anxiety disorders or other psychiatric disorders (e.g. depression) across the lifespan. Therefore, next to the identification of risk factors, preventive measures are needed in order to increase resilience in at-risk populations and are thus clinically and biologically investigated by our group.
   

Research projects

Ongoing

• 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, 3rd funding period 2016-2020; together with PD Dr. S. Neufang)
• Gene-environment interactions, neural circuits and generalization in dimensional endophenotypes of anxiety in adults and children: Development and reversibility (SFBTRR-58, project Z02, 3rd funding period 2016-2020; together with Prof. Dr. U. Lüken, Prof. Dr. Dr. U. Dannlowski, Dr. T. Lonsdorf, Prof. Dr. M. Romanos, Prof. Dr. P. Pauli, Prof. Dr. J. Deckert)
• (Epi)genetic effects related to extinction learning and outcome (PROTECT-AD, project P5, 2015-2018; together with Prof. Dr. J. Deckert)

Recently completed

• Epigenetic profiling of anxiety: the role of DNA methylation in the pathogenesis and therapeutic mechanisms of anxiety disorders (SFBTRR-58, project C02, 2nd funding period 2013-2016; together with Prof. Dr. K.P. Lesch, Prof. Dr. J. Deckert)
• Anxiety and emotional perception – Modulation by the adenosine, dopamine and endocannabinoid system (SFBTRR-58, project C02, 1st funding period 2008-2012; together with Prof. Dr. J. Deckert)
   

Selected publications

• Baune BT, Hohoff C, Berger K, Neumann A, Mortensen S, Roehrs T, Deckert J, Arolt V, Domschke K (2008) Association of the COMT val158met variant with antidepressant treatment response in Major Depression. Neuropsychopharmacology 33:924-932.
• Domschke K, Akhrif A, Bajer C, Mainusch M, Romanos M, Winkelmann J, Zimmer C, Neufang S (2015) Neuropeptide S receptor gene modulates the development of fronto-limbic effective connectivity. Cereb Cortex, bhv259.
• 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 (2012a) 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.
• Schartner C, Ziegler C, Schiele MA, Kollert L, Weber H, Zwanzger P, Arolt V, Pauli P, Deckert J, Reif A, Domschke K (2017) CRHR1 promoter hypomethylation: An epigenetic readout of panic disorder? Eur Neuropsychopharmacol 27(4):360-71.
• Schiele MA, Costa B, Abelli M, Martini C, Baldwin DS, Domschke K, Pini S (2018) Oxytocin receptor gene variation, behavioural inhibition, and adult separation anxiety: Role in complicated grief. World J Biol Psychiatry doi: 10.1080/15622975.2018.1430374.
• Schiele MA, Kollert L, Lesch KP, Arolt V, Zwanzger P, Deckert J, Ziegler C, Domschke K (2019). Hypermethylation of the serotonin transporter gene promoter in panic disorder - Epigenetic imprint of comorbid depression? Eur Neuropsychopharmacol 29(10):1161-1167.
• 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 doi: 10.1093/ijnp/pyy050 *equal contribution
• 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(1):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.
• Ziegler C, Wolf C, Schiele MA, Feric Bojic E, Kucukalic S, Sabic Dzananovic E, Goci Uka A, Hoxha B, Haxhibeqiri V, Haxhibeqiri S, Kravic N, Muminovic Umihanic M, Cima Franc A, Jaksic N, Babic R, Pavlovic M, Warrings B, Bravo Mehmedbasic A, Rudan D, Aukst-Margetic B, Kucukalic A, Marjanovic D, Babic D, Bozina N, Jakovljevic M, Sinanovic O, Avdibegovic E, Agani F, Dzubur-Kulenovic A, Deckert J, Domschke K (2018) Monoamine Oxidase A Gene Methylation and Its Role in Posttraumatic Stress Disorder: First Evidence from the South Eastern Europe (SEE)-PTSD Study. Int J Neuropsychopharmacol 21: 423-432.

PubMed

Funding

• Deutsche Forschungsgemeinschaft (DFG), Collaborative Research Centre SFBTRR-58 “Fear, Anxiety, Anxiety Disorders”
• Bundesministerium für Bildung und Forschung (BMBF), PROTECT-AD
• European Union (EU), EUSARNAD, FP7-PEOPLE-2010-IRSES
• Interdisziplinäres Zentrum für Klinische Forschung (IZKF), Würzburg

Cooperations and Networks

• DFG Sonderforschungsbereich SFB/Transregio 58 "Furcht, Angst, Angsterkrankungen"
• BMBF Forschungsverbund PROTECT-AD
• Gesellschaft für Angstforschung (GAF)
• Anxiety Disorders Research Network (ADRN; EU-Netzwerkinitiative) des European College of Neuropsychopharmacology (ECNP)