Lab for Systems Neurobiology

Theme and Objectives

Our research is aimed at an improved understanding of the neurobiology of mental illness, the course of illness and the response and side-effects of pharmacological and non-pharmacological interventions.

The understanding of the complex neurobiological and environmental (and their interaction) underpinnings of mental disorders has grown in light of technological advances in biology, neuroscience and bioinformatics in recent years. However, despite important progress namely on the identification of contributing multiple genes to mental disorders, a reductionistic and experimental research approach alone appears not sufficient to explain the development and the course of mental illness as well as the variation in response to pharmacological and non-pharmacological treatments. 

Systems neurobiology deals with complex biological systems at the levels of the entire organism, the brain, the tissue and the cell. Their characteristics and behaviour are more than the sum of their single individual linear functions. Commonly, systems neurobiology is defined as ”Computational Neurobiology“, where the complexity of neurobiological underpinnings is modelled using advanced bioinformatic approaches.

Such an understanding of systems neurobiology translates to the context of mental illness in that it is assumed that biologically related multimodal data such as genomic, transcriptomic, epigenomic and proteomic data represent the complex neurobiology and relate more likely to the extensive clinical phenotype of mental illness rather than by individual marker. From this complex neurobiological data, multiple methods of data reduction are employed to identify a smaller set of biologically validated and interrelated marker and vice versa, individual marker can be analysed in a systemic way using multimodal data.

Following this approach, this lab conducts a variety of experimental and interventional animal and human studies that generate multimodal biological and phenotypical data suited for systems biology analyses. Hence, the multidisciplinary lab team includes experts in the fields of biology, psychology, physicians, psychiatrists, animal and human-experimental neuroscientists and bioinformaticians. In addition, the lab has extensive experience in biobanking and managing large scale human projects, lab members take leadership roles in international research consortia such as GenECT-ic and a pharmacogenomic/transcriptomic ECNP network and make contributions as PIs to the PGC and ENIGMA consortia.

Team

  • Prof. Dr.med. Bernhard Baune, Lab Head
  • Bettina Walden, M.A., Administrative Support
  • Dr. rer. nat. Christa Hohoff (Dipl.-Biol.), Post-doc
  • Dr. Matthew Knight, affiliated Post-doc
  • Dr. Celia Fourrier, affiliated Post-doc
  • Dr. Julie Morgan, affiliated Post-doc
  • MTA Kathrin Schwarte, Technical Assistant
  • CTA Christiane Schettler, Technical Assistant
  • M.Sc. Biol. Nicole Kerkenberg, PhD candidate
  • Gaurav Singhal, PhD candidate
  • Emma Sampson, PhD candidate
  • Liliana Ciobanu, PhD candidate
  • Micah Cearns, PhD candidate
  • Andrew Olagunju, PhD candidate
  • Cand. med. Eva Schifferdecker, SHK
  • Jonas Plate, SHK

Projects

  • Microstructural brain changes depending on age, stress and genes and their impact on anxiety- and depression-like behaviour in a mouse model
  • Identification of epigenetics of resilience in a mouse model  
  • Analyses of circRNAs as biomarkers of psychiatric disorders
  • Interaction between epigenetic and acute and chronic environmental factors in the etiology / development and course of mental illness
  • Impact of genetic variants on the development of depression, bipolar disorder and schizophrenia
  • Genomics of response and side-effects to ECT in the Genomics of ECT international consortium (GenECT-ic) (Lead PI: Bernhard Baune)
  • Transdiagnostic genomic and transcriptomic analyses of pharmacological response to treatment (European ECNP network; Lead PI: Bernhard Baune)
  • Neurobiology of anti-inflammatory intervention on immune function and clinical response in depression (PREDDICT)
  • Neurobiology of cognitive and general function in mood disorders (COFAMS)
  • Neurobiology of effects of cognitive, emotional and social cognitive training intervention in depression (CERT-D)
  • Study of genetically modified mouse models of TNF (Tumor necrosis factor alpha) and its receptors TNFR1 and TNFR2 on behaviour, neurodegeneration, immune function
  • Behavioural and neurobiological analyses of the effects of TNF overexpression in the brain
  • Genomics and transcriptomics of lithium treatment response in bipolar disorders
  • Investigation of complement factors in mental illness: schizophrenia and depression
  • Immune genomics of depression
  • Neurobiology of cognitive function across mental disorders
  • Neurobiological effects of exercise and environmental enrichment on brain function
  • Trauma and genetic interaction in depression
  • GWAS of cognitive function in depression
  • Neurobiological underpinnings of psychosocial functional outcomes in depression, bipolar disorder and schizophrenia

Research projects for higher degree students

We are regularly seeking research students from the fields of neuroscience, biology, psychology and medicine and related fields who are interested in obtaining a research degree such as PhD, Dr.med./MedK, Master or Bachelor degrees.

Students are encouraged to contact the lab head to discuss any of the above projects or to develop a new project jointly with their prospective supervisor. The lab division encourages and actively supports students to publish their project results in peer-review journals. Research students will be given access to a range of research methodologies and will be trained and supervised in the techniques relevant to their field of research. In a collaborative and interdisciplinary setting, the students will be equipped with highly relevant lab, research and writing skills as well as interdisciplinary research that makes it an enriching learning experience that prepares them ideally for their future careers.

The broad methodological spectrum of the multi-skilled interdisciplinary lab group includes genetically modified mouse models, behavioural research methodologies in small animals, neuroimaging (MRT), immune-histochemistry, FACS analyses, cellular analytic methods, pharmacogenomics, transcriptomics, epigenomics, proteomics both in animal and human studies as well as bioinformatic skills. The lab members have particular skills in managing a large scale biobank for local and international projects.

Current funding

  • National Health and Research Council (NHMRC)
  • Fay Fuller Foundation
  • James and Diana Ramsay Foundation
  • Rolf Dierichs-Foundation

Current selected publications

  1. Hohoff C, Zhang M, Ambrée O, Kravchenko M, Buschert J, Kerkenberg N, Gorinski N, Abdel Galil D, Schettler C, Vom Werth KL, Wewer MF, Schneider I, Grotegerd D, Wachsmuth L, Faber C, Skryabin BV, Brosius J, Ponimaskin E, Zhang W (2019) Deficiency of the palmitoyl acyltransferase ZDHHC7 impacts brain and behavior of mice in a sex-specific manner. Brain Struct Funct 224(6):2213-2230; https://www.ncbi.nlm.nih.gov/pubmed/31183559
  2. Ciobanu LG, Sachdev PS, Trollor JN, Reppermund S, Thalamuthu A, Mather KA, Cohen-Woods S, Stacey D, Toben C, Schubert KO, Baune BT. Co-expression network analysis of peripheral blood transcriptome identifies dysregulated protein processing in endoplasmic reticulum and immune response in recurrent MDD in older adults. J Psychiatr Res. 2018 Dec;107:19-27; https://www.ncbi.nlm.nih.gov/pubmed/30312913
  3. Singhal G, Morgan J, Jawahar MC, Corrigan F, Jaehne EJ, Toben C, Breen J, Pederson SM, Hannan AJ, Baune BT. (2019) The effects of short-term and long-term environmental enrichment on locomotion, mood-like behavior, cognition and hippocampal gene expression. Behav Brain Res. 2019 Aug 5;368:111917. doi: 10.1016/j.bbr.2019.111917.
  4. Morgan JA, Singhal G, Corrigan F, Jaehne EJ, Jawahar MC, Breen J, Pederson S, Baune BT. (2019) Ceasing exercise induces depression-like, anxiety-like, and impaired cognitive-like behaviours and altered hippocampal gene expression. Brain Res Bull. 2019 May;148:118-130. doi: 10.1016/j.brainresbull.2019.02.014.
  5. Morgan JA, Singhal G, Corrigan F, Jaehne EJ, Jawahar MC, Baune BT. (2018) TNF signalling via the TNF receptors mediates the effects of exercise on cognition-like behaviours. Behav Brain Res. 2018 Nov 1;353:74-82. doi: 10.1016/j.bbr.2018.06.036.
  6. Stacey D, Schubert KO, Clark SR, Amare AT, Milanesi E, Maj C, Leckband SG, Shekhtman T, Kelsoe JR, Gurwitz D, Baune BT. A gene co-expression module implicating the mitochondrial electron transport chain is associated with long-term response to lithium treatment in bipolar affective disorder. Transl Psychiatry. 2018 Sep 5;8(1):183; https://www.ncbi.nlm.nih.gov/pubmed/30185780
  7. Amare AT, Schubert KO, Hou L, Clark SR, Papiol S, Heilbronner U, Degenhardt F, Tekola-Ayele F, Hsu YH, Shekhtman T, Adli M, Akula N, Akiyama K, Ardau R, Arias B, Aubry JM, Backlund L, Bhattacharjee AK, Bellivier F, Benabarre A, Bengesser S, Biernacka JM, Birner A, Brichant-Petitjean C, Cervantes P, Chen HC, Chillotti C, Cichon S, Cruceanu C, Czerski PM, Dalkner N, Dayer A, Del Zompo M, DePaulo JR, Étain B, Falkai P, Forstner AJ, Frisen L, Frye MA, Fullerton JM, Gard S, Garnham JS, Goes FS, Grigoroiu-Serbanescu M, Grof P, Hashimoto R, Hauser J, Herms S, Hoffmann P, Hofmann A, Jamain S, Jiménez E, Kahn JP, Kassem L, Kuo PH, Kato T, Kelsoe J, Kittel-Schneider S, Kliwicki S, König B, Kusumi I, Laje G, Landén M, Lavebratt C, Leboyer M, Leckband SG, Tortorella A, Manchia M, Martinsson L, McCarthy MJ, McElroy S, Colom F, Mitjans M, Mondimore FM, Monteleone P, Nievergelt CM, Nöthen MM, Novák T, O'Donovan C, Ozaki N, Ösby U, Pfennig A, Potash JB, Reif A, Reininghaus E, Rouleau GA, Rybakowski JK, Schalling M, Schofield PR, Schweizer BW, Severino G, Shilling PD, Shimoda K, Simhandl C, Slaney CM, Squassina A, Stamm T, Stopkova P, Maj M, Turecki G, Vieta E, Volkert J, Witt S, Wright A, Zandi PP, Mitchell PB, Bauer M, Alda M, Rietschel M, McMahon FJ, Schulze TG, Baune BT. Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study. JAMA Psychiatry. 2018 Jan 1;75(1):65-74; https://www.ncbi.nlm.nih.gov/pubmed/29121268
  8. Schneider I, Kugel H, Redlich R, Grotegerd D, Bürger C, Bürkner PC, Opel N, Dohm K, Zaremba D, Meinert S, Schröder N, Straßburg AM, Schwarte K, Schettler C, Ambrée O, Rust S, Domschke K, Arolt V, Heindel W, Baune BT, Zhang W, Dannlowski U, Hohoff C (2018) Association of Serotonin Transporter Gene AluJb Methylation with Major Depression, Amygdala Responsiveness, 5-HTTLPR/rs25531 Polymorphism, and Stress. Neuropsychopharmacology 43(6):1308-1316; https://www.ncbi.nlm.nih.gov/pubmed/29114103
  9. Dannlowski U, Kugel H, Grotegerd D, Redlich R, Opel N, Dohm K, Zaremba D, Grögler A, Schwieren J, Suslow T, Ohrmann P, Bauer J, Krug A, Kircher T, Jansen A, Domschke K, Hohoff C, Zwitserlood P, Heinrichs M, Arolt V, Heindel W, Baune BT. (2016) Disadvantage of Social Sensitivity: Interaction of Oxytocin Receptor Genotype and Child Maltreatment on Brain Structure. Biol Psychiatry. 2016 Sep 1;80(5):398-405. doi: 10.1016/j.biopsych.2015.12.010; https://www.ncbi.nlm.nih.gov/pubmed/26858213
  10. Hohoff C, Weber H, Richter J, Domschke K, Zwanzger PM, Ohrmann P, Bauer J, Suslow T, Kugel H, Baumann C, Klauke B, Jacob CP, Fritze J, Bandelow B, Gloster AT, Gerlach AL, Kircher T, Lang T, Alpers GW, Ströhle A, Fehm L, Wittchen HU, Arolt V, Pauli P, Hamm A, Reif A, Deckert J. (2015) RGS2 genetic variation: Association analysis with panic disorder and dimensional as well as intermediate phenotypes of anxiety. Am J Med Genet B Neuropsychiatr Genet. 2015 Apr;168(3):211-22, https://www.ncbi.nlm.nih.gov/pubmed/25740197
  11. Dannlowski U, Grabe HJ, Wittfeld K, Klaus J, Konrad C, Grotegerd D, Redlich R, Suslow T, Opel N, Ohrmann P, Bauer J, Zwanzger P, Laeger I, Hohoff C, Arolt V, Heindel W, Deppe M, Domschke K, Hegenscheid K, Völzke H, Stacey D, Meyer zu Schwabedissen H, Kugel H, Baune BT. (2015) Multimodal imaging of a tescalcin (TESC)-regulating polymorphism (rs7294919) – specific effects on hippocampal gray matter structure. Mol Psychiatry. 2015 Mar;20(3):398-404, https://www.ncbi.nlm.nih.gov/pubmed/24776739
  12. Hohoff C, Garibotto V, Elmenhorst D, Baffa A, Kroll T, Hoffmann A, Schwarte K, Zhang W, Arolt V, Deckert D, Bauer A.  (2014) Association of adenosine receptor gene polymorphisms and in vivo adenosine A1 receptor binding in the human brain. Neuropsychopharmacology. 2014 Dec;39(13):2989-99, https://www.ncbi.nlm.nih.gov/pubmed/24943643
  13. Dannlowski U, Kugel H, Redlich R, Halik A, Schneider I, Opel N, Grotegerd D, Schwarte K, Schettler C, Ambrée O, Rust S, Domschke K, Arolt V, Heindel W, Baune BT, Suslow T, Zhang W, Hohoff C. (2014) Serotonin transporter gene methylation is associated with hippocampal gray matter volume. Hum Brain Mapp. 2014 Nov;35(11):5356-67; https://www.ncbi.nlm.nih.gov/pubmed/24862560
 
 
 
 

Univ.-Prof. Dr. med. Bernhard Baune, MPH, MBA, FRANZCP
Tel.: +49 (0) 251 / 83-56664
E-Mail: bernhard.baune(at)­ukmuenster(dot)­de
CV


Administraion assistance:
Mrs. T. Hochstrate
Tel.: +49 (0)251 / 83-56664
Fax: +49 (0)251 / 83-57128
E-Mail: sekrebaune(at)­ukmuenster(dot)­de