TRiP research group

TRiP

Biomarkers for Mental Disorders

Today the diagnosis of most psychiatric disorders is based mainly on clinical examination. As in other fields of medicine, the identification of biological markers can provide a more objective access to diagnosis and it can help to confirm the clinical diagnosis. Biological markers may also allow to track disease progression and treatment success in an objective manner.

We therefore have a close cooperation with international research groups of the Cambridge Center for Neuropsychiatric Research CCNR der University of Cambridge (Head: Prof. Dr. Sabine Bahn, MD PhD) and the Schizophrenia Center and Program in Molecular Psychiatry – Johns Hopkins University, Baltimore, MD, USA (Director: Prof. Akira Sawa, MD PhD) to identify some biomarker profiles for psychiatric disorders. We were able to detect two first biomarkerprofiles in the cerebrospinal fluid (CSF) of patients with first-episode schizophrenic psychosis. These profiles are considered to be promising candidates for the development of generally available diagnostic tests.

Founded by the European Commission, we were able to continue our work as part of a European research project (SchizDX).

We are currently continuing our biomarker research in collaboration with the Johns Hopkins University.

Funding:

This research was funded by the Stanley Medical Research Institute of teh Theodore and Vada Stanley Foundation, USA (Grant IDs 01-315 and 03-NV-003 to FML) and European Commission (SchizDX EU FP7 HEALTH-F4-2009-223427).

Selected Publications

J. Cooper, S. Ozcan, R. Gardner, N. Rustogi, S. Wicks, G. van Rees, C. Dalman, H. Karlsson, F. M. Leweke, S. Bahn: Schizophrenia-risk and urban birth are associated with proteomic changes in neonatal dried blood spots. Transl Psychiatry (2017) in press

G. Kannan, K. L. Gressitt, S. Yang, C. R. Stallings, E. Katsafanas, L. A. Schweinfurth, C. L. G. Savage, M. B. Adamos, K. M. Sweeney, A. E. Origoni, S. Khushalani, S. Bahn, F. M. Leweke, F. B. Dickerson, R. H. Yolken, M. V. Pletnikov, E. G. Severance: Pathogen-mediated NMDA receptor autoimmunity and cellular barrier dysfunction in schizophrenia. Transl Psychiatry (2017) 7:e1186

J. M. Coughlin, L. N. Hayes, T. Tanaka, M. Xiao, R. H. Yolken, P. Worley, F. M. Leweke, A. Sawa: Reduced superoxide dismutase-1 (SOD1) in cerebrospinal fluid of patients with early psychosis in association with clinical features. Schizophr Res (2017) 183:64-69

J. M. Bumb, D. Mier, I. Noelte, M. Schredl, P. Kirsch, O. Hennig, L. Liebrich, S. Fenske, B. Alm, C. Sauer, F. M. Leweke, E. Sobanski: Associations of pineal volume, chronotype and symptom severity in adults with attention deficit hyperactivity disorder and healthy controls. Eur Neuropsychopharmacol (2016) 26:1119-1126

J. M. Bumb, F. Enning, J. K. Mueller, T. van der List, C. Rohleder, P. Findeisen, I. Noelte, E. Schwarz, F. M. Leweke: Differential melatonin alterations in cerebrospinal fluid and serum of patients with major depressive disorder and bipolar disorder. Comp Psychiatry (2016) 68:34-39

E. Severance, K. Gressitt, C. Stallings, E. Katsafanas, L. Schweinfurth, C. Savage, M. Banis, K. Sweeney, A. Origoni, S. Khushalani, F. M. Leweke, F. Dickerson, R. H. Yolken: Candida albicans exposures, sex specificity and cognitive deficits in schizophrenia and bipolar disorder. (2016) npj Schizophrenia 2:16018

J. Tomasik, E. Schwarz, S. G. Lago, M. Rothermundt, F. M. Leweke, N. J. M. van Beveren, P. C. Guest, H. Rahmoune, J. Steiner, S. Bahn: Pretreatment levels of the fatty acid handling proteins H-FABP and CD36 predict response to olanzapine in recent-onset schizophrenia patients. (2016) Brain Behav Immun 52:178-186

F. Haenisch, J. D. Cooper, A. Reif, S. Kittel-Schneider, J. Steiner, F. M. Leweke, M. Rothermundt, N. J. M. van Beveren, B. Crespo-Facorro, D. W. Niebuhr, D. N. Cowan, N. S. Weber, R. H. Yolken, B. W. J. H. Penninx, S. Bahn: Towards a blood-based diagnostic panel for bipolar disorder. Brain Behav Immun (2016) 52:49-57

M. K. Chan, M.-O. Krebs, D. Cox, P. C. Guest, R. H. Yolken, H. Rahmoune, M. Rothermundt, J. Steiner, F. M. Leweke, N. J. M. van Beveren, D. W. Niebuhr, N. S. Weber, D. N. Cowan, B. Crespo-Facorro, C. Mam-Lam-Fook, J. Bourgin, P. Suarez-Pinella, R. J Wenstrup, R. R. Kaldate, J. D. Cooper, S. Bahn: Development of a blood-based molecular biomarker test for identification of schizophrenia prior to disease onset. Transl Psychiatry (2015) 5, e601

M. Bot, M. K. Chan, R. Jansen, F. Lamers, N. Vogelzangs, F. M. Leweke, M. Rothermundt, J. Steiner, J. Cooper, S. Bahn, B. W. J. H. Penninx: Peripheral proteomic profiling of major depressive disorder. Transl Psychiatry (2015) 5, e599

J. A. Jaros, H. Rahmoune, H. Wesseling, M. Rothermundt, F. M. Leweke, P. C. Guest, S. Bahn (2015) Olanzapine treatment of schizophrenia patients induces alterations in serum protein phosphorylation patterns. Proteomics Clin Appl (2015) 9:907-916

G. Fond, M.-A. d’Albis, S. Jamain, R. Tamouza, C. Arango, W. W. Fleischhacker, B. Glenthøj. F. M. Leweke, S. Lewis, P. McGuire, A. Meyer-Lindenberg, I. E. Sommer, I. Winter-van Rossum, S. Kapur, R. S. Kahn, D. Rujescu, M. Leboyer: The promise of biological markers for treatment response in first-episode psychosis: a systematic review. Schizophr Bull (2015) 41:559-573

E. G. Severance, K. L. Gressitt, A. Alaedini, J. M. Bumb, J. K. Mueller, F. Enning, R. H. Yolken, F. M. Leweke: IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia. Br Behav Immunity (2015) 44:148-58.

M. Grosshans, E. Schwarz, J. M. Bumb, C. Schaefer, S. Vollstädt-Klein, H. Tost, A. Meyer-Lindenberg, F. Kiefer, F. M. Leweke: Understanding the role of oleoylethanolamide in obesity: differential association with body mass index and food cue-induced brain activation. JAMA Psychiatry (2014) 71:1254-1261

L. N. Hayes, E. G. Severance, J. T. Leek, K. L. Gressitt, C. Rohleder, J. M. Coughlin, F. M. Leweke, R. H. Yolken, A. Sawa: Inflammatory molecular signature associated with infectious agents in psychosis. Schizophr Bull (2014) 40:963-972.

E. Schwarz, J. M. van Beveren, J. Ramsey, F. M. Leweke, M. Rothermundt, B. Bogerts, J. Steiner, P. C. Guest, S. Bahn: Identification of molecular subgroups of schizophrenia patients. Schizophr Bull (2014) 40:787-795.

J. Coughlin, K. Ishizuka, S.-I. Kano, J. Edwards, F. Seifuddin, M. Shimano, E. Daley, P. Zandi, F. M. Leweke, N. Cascella, M. Pomper, R. Yolken, A. Sawa: Marked reduction of soluble superoxide dis-mutase-1 (SOD1) in cerebrospinal fluid of patients with recent-onset schizophrenia. Mol Psychiatr (2013) 18:10-11.

J. M. Ramsey, E. Schwarz, P. C. Guest, N. J. van Beveren, F. M. Leweke, M. Rothermundt, B. Bogerts, J. Steiner, L. Ruta, S. Baron-Cohen, S. Bahn: Molecular sex differences in human serum. PLoS One, 7 (2012), e51504.

E. Schwarz, P. C. Guest, H. Rahmoune, L. W. Harris, L. Wang, F. M. Leweke, M. Rothermundt, B. Bogerts, D. Koethe, L. Kranaster, P. Ohrmann, T. Suslow, G. McAllister, M. Spain, A. Barnes, N. J. van Beveren, S. Baron-Cohen, J. Steiner, F. E. Torrey, R. H. Yolken, S. Bahn: Identification of a biological signature for schizophrenia in serum. Mol Psychiatr (2012) 17: 494-502.

M. Herberth, D. Koethe, T. M. Cheng, N. D. Krzyszton, S. Schoeffmann, P. C. Guest, H. Rahmoune, L. W. Harris, L. Kranaster, F. M. Leweke, S. Bahn: Impaired glycolytic response in peripheral blood mo-nonuclear cells of first-onset antipsychotic-naive schizophrenia patients. Mol Psychiatr (2011) 16: 848-859.

Y. Levin, L. Wang, E. Schwarz, D. Koethe, F. M. Leweke, S. Bahn: Global proteomic profiling reveals altered proteomic signature in schizophrenia serum. Mol Psychiatr (2010) 15: 1088-1100.

P. C. Guest, L. Wang, L.W. Harris, K. Burling, Y. Levin, A. Ernst, M. T. Wayland, Y. Umrania, M. Her-berth, D. Koethe, J. M. van Beveren, M. Rothermundt, G. McAllister, F. M. Leweke, J. Steiner, S. Bahn: Increased levels of circulating insulin-related peptides in first onset, antipsychotic naïve schizophrenia patients. Mol Psychiatr (2010) 15: 118-119.

M. Herberth, D. N. Krzyszton, D. Koethe, M. R. Craddock, E. Bulger, E. Schwarz, P. Guest, F. M. Le-weke, S. Bahn: Differential effects on T-cell function following exposure to serum from schizophrenia smokers. Mol Psychiatr (2010) 15: 364-371.

J. T.-J. Huang, L. Wang, M. Wengenroth, D. Koethe, C. W. Gerth, S. Gross, D. Schreiber, F. M. Lewe-ke, S. Bahn: Independent protein profiling studies show a decrease in apolipoprotein A1 levels in CSF and peripheral tissues. Mol Psychiatr (2008) 13: 1118-1128.

J. T.-J. Huang, F. M. Leweke, D. Oxley, L. Wang, N. Harris, D. Koethe, C. W. Gerth, B. M. Nolden, S. Gross, D. Schreiber, S. Bahn: Identification of diagnostic biomarkers for first-onset schizophrenia. PLoS Medicine (2006) 3(11): e428:1-14.

E. Holmes, T. M. Tsang, J. T.-J. Huang, F. M. Leweke, D. Koethe, C. W. Gerth, B. M. Nolden, S. Gross, D. Schreiber, S. Bahn: Metabolic profiling of CSF: evidence that early intervention may impact on disease progression and outcome in schizophrenia. PLoS Medicine (2006) 3(8), e327:1-9.