Molecular Precision Mental Health - 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 established our lab (mpmh.me and mypmh.me) at the Charles Perkins Centre of the University of Sydney in close collaboration with Sydney Mass Spectrometry, where we are focused on lipidomic and x-omic investigations of human and animal tissues. Our goal is to contribute to a more personalized assessment and treatment of mental health and disorders.
In close cooperation with international research groups, currently the Schizophrenia Center and Program in Molecular Psychiatry – Johns Hopkins University, Baltimore, MD, USA (Director: Prof. Akira Sawa, MD PhD) and previously the Cambridge Center for Neuropsychiatric Research CCNR der University of Cambridge (Head: Prof. Dr. Sabine Bahn, MD PhD), we have identified fluid biomarker profiles for psychiatric disorders.
We were able to detect two first biomarker profiles in the cerebrospinal fluid (CSF) of patients with first-episode schizophrenic psychosis. These profiles delivered the basis for the development of blood based biomarker tests, resulting from a European research project (SchizDX), founded by the European Commission.
Funding:
This research was funded by the Stanley Medical Research Institute of the 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
A. Moldavski, H. Wenz, B. Lange, C. Rohleder, F. M. Leweke. Case Report: Severe adolescent major depressive syndrome turns out to be an unusual case of Anti-NMDA receptor encephalitis. (2021) Front Psychiatry 12: 679996.
C. G. Bien, C. Rohleder, J. E. Mueller, C. I. Bien, D. Koethe, F. M. Leweke: Neural autoantibodies in cerebrospinal fluid and serum in clinical high risk for psychosis, first-episode psychosis, and healthy volunteers. Front Psychiatry (2021) 12:654602
J. Cooper, S. Han, J. Tomasik, S. Ozcan, N. Rustogi, N. van Beveren, F. M. Leweke, S. Bahn: Multimodel inference for biomarker development: an application to schizophrenia. Transl Psychiatry (2019) 9:83
T. Grent-‘t-Jong, J. Gross, J. Goenze, M. Wibral, R. Gajwani, A. Gumley, S. M. Lawrie, M. Schwan-nauer, F. Schultze-Lutter, D. Koethe, F. M. Leweke, W. Singer, P. J. Uhlhaas: Resting-state gamma-band power alterations in schizophrenia reveal e/i-balance abnormalities across ill-ness-stages. eLife (2018) Sep 27;7: e37799
G. F. van Rees, S. G. Lago, D. A. Cox, J. Tomasik, N. Rustogi, K. Weigelt, S. Ozcan, J. D. Cooper, H. Drexhage, F. M. Leweke, S. Bahn: Evidence of microglial activation following exposure to serum from first-onset drug-naïve schizophrenia patients. Brain Behav Immun (2018) 67:364–373
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) 7:e1290
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.