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Personalized Therapy of Affective Disorders

Research group leader:

Andreas Menke, M.D. (CV)
Twitter: @Dr_A_Me

AG Wein am Stein

Staff

Dipl.-Psych. Catharina Wurst
E-Mail: Wurst_C@ukw.de

Carolin Leistner
E-Mail: Leistner_C@ukw.de

Dr. Yasmin Busch
E-Mail: Busch_Y@ukw.de

Dipl.-Psych. J. Reitz
E-Mail: Reitz_J@ukw.de

Cand med. Dominik Lehrieder
E-Mail: E_Lehriede_D@ukw.de

Cand. med. Karin Lechner
E-Mail: E_Lechner_K@ukw.de

Cand. med. Amelie Sauter
E-Mail: E_Sauter_A@ukw.de

Ms. Tamara Thauer
E-Mail: Thauer_T@ukw.de

Ms. Sandra Scheder
E-Mail: Scheder_S1@ukw.de

Ms. Jasmin Fietz
E-Mail: E_Fietz_J@ukw.de

Ms. Lisa Frieß
E-Mail: Friess_L1@ukw.de

Ms. Carolin Burschka
E-Mail: Burschka_C@ukw.de

Contact:

Priv.-Doz. Dr. med. Andreas Menke
Department of Psychiatry, Psychosomatics and Psychotherapy
University Hospital Wuerzburg
Margarete-Hoeppel-Platz 1
97080 Wuerzburg

Menke_A@ukw.de
Tel: 0931-201-76050; Fax: 0931-201-6076343

Research Focus:

Mood disorders like depressive and bipolar (i.e. manic-depressive) disorders are predicted to become a leading cause of mortality and morbidity world-wide. They impair patient’s mood, cognition, functioning and social relations and may result in suicidal behavior. Despite this tremendous impact, the pathogenesis of affective disorders remains poorly understood. Even with the advent of DSM-5, no diagnostic parameters derived from peripheral blood, brain imaging, or genomics have been established for diagnosing affective disorders. Additionally, the efficacy of treatment with novel antidepressants in daily practice is questioned once in a while. Since antidepressant drugs were introduced into the clinic in the 1950s there has been little improvement in efficacy, only side effects were significantly reduced. Hence, there is still great need to further intensify efforts to expand the understanding of the pathophysiology and treatment of mood disorders.

An in-depth understanding of the pathophysiological mechanisms of affective disorders would provide the development of treatments which are indeed targeted to the biological sources of the disease state. Unlike other disciplines of medicine the diagnostic process in psychiatry is based solely on clinical judgment, without incorporating lab-derived objective measures. However, it has become increasingly clear that the current used diagnostic categories possibly include patients with similar symptoms but divergent underlying biology. Contrary, studies suggest that the same biological alterations produce a variety of different symptoms. Therefore, a combination of symptom-based and biology-based diagnostic categories would facilitate the understanding of the underlying pathogenetic mechanisms of mood disorders and enable an expansion of treatment strategies. By using biomarkers an in-depth characterization of the patients would enable a personalized medicine, which incorporates environmental and developmental factors.  

The overarching aim is to apply biomarker-based approaches for a new taxonomy of mood disorders. This transdiagnostic characterization of patients may help to identify underlying biological signatures and subsequently facilitate personalized treatment algorithms. 

For the identification of the biological trajectories the current projects include the following interlinked topics:

  1. Hypothalamic-Pituitary-Adrenal (HPA-) Axis
    The functioning of the HPA-axis, especially the sensitivity of the glucocorticoid receptor (GR) will be characterized on a neuroendocrinological basis (measurement of cortisol, ACTH levels) and genetical basis (GR-induced mRNA expression and methylation of candidate genes, e.g. FKBP5).
  2. Immune signaling
    
Inflammatory markers may be elevated in stress-associated disorders, therefore alterations of leucocytes, CRP, TNF-a, IL-1a, IL-1b, IL-2, IL-6, IL-10 in peripheral blood are measured
  3. Autonomic nervous system
    For evaluation of the adrenergic nervous system norepinephrine in plasma and heart rate variability are analyzed amongst other parameters.
  4. Relation of stress-associated psychiatric disorders with somatic diseases (e.g. chronic heart failure in cooperation with the Comprehensive Heart Failure Center)

    Several studies demonstrated that depressive symptoms in patients suffering from chronic heart failure were common and independent predictors for both poor outcome and increased use of healthcare resources. On the other hand, depressive episodes are associated with an increased risk of developing cardiac sequelae, including heart failure. Biomarker-based approaches of the above mentioned stress-systems should help to identify factors contributing to psychiatric and heart diseases and thus improve treatment options.

Project funding

  • Depression associated cardiac failure (DACFAIL), BMBF/DLR
  • Determining the reciprocal relationship between heart failure and brain function, BMBF/DLR
  • Cerebral serotonin transporter availability as treatment guidance for patients with anxious depression, IZKF
  • Predicting Response to Depression Treatment (PReDicT), P1vital, UK

Selected publications:

  1. Menke, Arloth, Best, Namendorf, Gerlach, Czamara, Lucae, Dunlop, Mletzko Crowe, Garlow, Nemeroff, Ritchie, Craighead, Mayberg, Rex-Haffner, Binder, Uhr; “Time-dependent effects of dexamethasone plasma concentrations on glucocorticoid receptor challenge tests”. (2016) Psychoneuroendocrinology, 69:161-171.
  2. Arloth, Bogdan, Weber, Frishman, Menke, Wagner, Balsevich, Schmidt, Karbalai, Czamara, Altmann, Trumbach, Wurst, Mehta, Uhr, Klengel, Erhardt, Carey, Conley, Major Depressive Disorder Working Group of the Psychiatric Genomics C, Ruepp A, Muller-Myhsok B, Hariri AR, Binder EB, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium PGC. “Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders”. (2015) Neuron 86:1189-1202. 
  3. Menke, Arloth, Gerber, Rex-Haffner, Uhr, Holsboer, Binder, Holsboer-Trachsler, Beck; “Dexamethasone Stimulated Gene Expression in Peripheral Blood Indicates Glucocorticoid-Receptor Hypersensitivity in Job-Related Exhaustion”. (2014) Psychoneuroendocrinology, 44: 35-46. . 
  4. Menke, Binder; “Epigenetic alterations in depression and antidepressant treatment”. (2014) Dialogues in Clinical Neuroscience, 16: 395-404.
  5. Menke; “Exploring the Genetic Landscape of Depression”. (2014) Ann Depress Anxiety, 1(2): 2.
  6. Menke; “Biomarkers for Taxonomy of Neuropsychiatric Diseases”. (2014) Austin Biomark Diagn, 1(2): 2.
  7. Issler, Harmati, Paul, Maeno, Navon, Zwang, Gil, Mayberg, Dunlop, Menke, Awatramani, Binder, Deneris, Lowry, Chen; “microRNA 135 is essential for chronic stress resiliency, antidepressant efficacy and intact serotonergic activity”. (2014) Neuron, 83(2):344-60.
  8. Menke; “Gene Expression: Biomarker of Antidepressant Therapy?”. (2013) International Review of Psychiatry, 25(5):579-91.
  9. Menke, Klengel, Rubel, Brückl, Pfister, Lucae, Uhr, Holsboer, Binder; “Genetic variation in FKBP5 is associated with the extent of stress hormone system dysregulation in major depression”. (2013) Genes, Brain & Behavior, 12(3): 289-96.
  10. Menke, Arloth, Pütz, Weber, Klengel, Mehta, Gonik, Rex-Haffner, Rubel, Uhr, Lucae, Deussing, Müller-Myhsok, Holsboer, Binder; “Dexamethasone stimulated gene expression in peripheral blood is a sensitive marker for glucocorticoid receptor resistance in depressed patients”. (2012) Neuropsychopharmacology, 37(6):1455-64.
  11. Menke, Domschke, Czamara, Klengel, Hennings, Lucae, Baune, Arolt, Müller-Myhsok, Holsboer, Binder; „Genome-wide association study of antidepressant treatment emergent suicidal ideation“. (2012) Neuropsychopharmacology, 37(3):797-807.
  12. Menke, Rex-Haffner, Klengel, Binder, Mehta; “Peripheral blood gene expression: it all boils down to the RNA collection tubes”. (2012) BMC Research Notes, 5:1.
  13. Menke, Klengel, Binder; “Epigenetics, depression and antidepressant treatment”. (2012) Current Pharmaceutical Design, 18, 5879-5889.
  14. Ganea, Menke, Schmidt, Lucae, Rammes, Liebl, Harbich, Sterlemann, Storch, Uhr, Holsboer, Binder, Sillaber, Müller; „Convergent animal and human evidence suggests the activin/inhibin pathway to be involved in antidepressant response”. (2012) Translational Psychiatry, 2:e177.
  15. Klengel, Menke; „Neurobiology of Depression“. (2012) DHZ, 2:14-18.
  16. Menke, Sämann, Kloiber, Czamara, Lucae, Hennings, Heck, Kohli, Czisch, Müller-Myhsok, Holsboer, Binder; “Polymorphisms within the metabotropic glutamate receptor 1 gene are associated with depression phenotypes”. (2011) Psychoneuroendocrinology, 37(4):565-75.
  17. Menke, Binder; “Genetics of Major Depression”. (2011) Psychotherapie, 16(2):247-264.
  18. Kohli, Lucae, Saemann, Schmidt, Demirkan, Hek, Roeske, Alexander, Salyakina, Ripke, Hoehn, Specht, Menke, Hennings, Heck, Wolf, Ising, Schreiber, Czisch, Müller, Uhr, Bettecken, Becker, Schramm, Rietschel, Maier, Bradley, Ressler, Nöthen, Cichon, Craig, Breen, Lewis, Hofman, Tiemeier, van Duijn, Holsboer, Müller-Myhsok, Binder; “The neuronal transporter gene SLC6A15 confers risk to major depression”. (2011) Neuron, 70(2): 252-265.
  19. Mehta, Gonik,  Klengel, Rex-Haffner, Menke, Rubel, Mercer, Pütz, Bradley, Holsboer,  Ressler, Müller-Myhsok, Binder; “Using polymorphisms in FKBP5 to define biologically distinct subtypes of posttraumatic stress disorder: evidence from endocrine and gene expression studies”. (2011) Archives of General Psychiatry, 68(9):901-10.
  20. Kohli, Salyakina, Pfennig, Lucae, Horstmann, Menke, Kloiber, Hennings, Bradley, Ressler, Uhr, Müller-Myhsok Holsboer, Binder; “Genetic variants in the neurotrophic receptor encoding gene NTRK2 are 2 associated with a life history of suicide attempts in depressed patients”. (2010) Archives of General Psychiatry, 67(4): 348-59.
  21. Mehta, Menke, Binder; „Gene Expression Studies in Major Depression“. (2009) Current Psychiatry Reports, 12: 135-144.
  22. Ising, Lucae, Binder, Bettecken, Uhr, Ripke, Kohli, Hennings, Horstmann, Kloiber, Menke, Bondy, Rupprecht, Domschke, Baune, Arolt, Rush, Holsboer & Müller-Myhsok; “A genome-wide association study points to multiple loci predicting treatment outcome in depression”. (2009) Archives of General Psychiatry, 66(9):966-975.
  23. Menke, Lucae, Kloiber, Horstmann, Bettecken, Uhr, Ripke, Ising, Müller-Myhsok, Holsboer & Binder; “Genetic markers within glutamate receptors are associated with antidepressant treatment emergent suicidal ideation”. (2008) American Journal of Psychiatry, 165:7,917-918.

Cooperations:

Prof. Dr. Dr. Elisabeth Binder, Max Planck Institute of Psychiatry, Munich, Germany
Dr. Johannes Beck, University Hospital of Basel, Department of Psychiatry, Basel, Switzerland