Molecular Precision Mental Health - Biomarkers for Mental Disorders
The current method for diagnosing most psychiatric disorders is through clinical examination. However, the identification of biological markers can provide an objective approach to diagnosis, confirming the clinical diagnosis and allowing for tracking of disease progression and treatment success. With this in mind, we have established our lab (mpmh.me) in collaboration with Sydney Mass Spectrometry at the Charles Perkins Centre of the University of Sydney, where we established a project node Molecular Precision Mental Health. Our focus is on lipidomic and x-omic investigations of human and animal tissues to contribute to a more personalized assessment and treatment of mental health and disorders.
We work closely with international research groups, such as the Schizophrenia Center and Program in Molecular Psychiatry at Johns Hopkins University, Baltimore, MD, USA (led by Prof. Akira Sawa, MD PhD), and previously the Cambridge Center for Neuropsychiatric Research CCNR at the University of Cambridge (led by Prof. Dr. Sabine Bahn, MD PhD). Through our collaborations, we have identified fluid biomarker profiles for psychiatric disorders.
Our team was able to detect two biomarker profiles in the cerebrospinal fluid (CSF) of patients with first-episode schizophrenic psychosis. These profiles formed the basis for the development of blood-based biomarker tests resulting from a European research project (SchizDX), which was funded 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
T. A. Couttas, B. Jieu, C. Rohleder, F. M. Leweke (2022) Mini review: Current state of fluid lipid biomarkers for personalized diagnostics and therapeutics in schizophrenia spectrum disorders and related psychoses. Front Psychiatry, 13:885904
T. A. Couttas, C. Boost, F. Pahlisch, E. B. Sykorova, D. Koethe, J. E. Leweke, H. Endepols, C. Rohleder, F. M. Leweke (2022) Simultaneous assessment of serum levels and pharmacologic effects of cannabinoids on endocannabinoids and N-acylethanolamines by liquid chromatography – tandem mass spectrometry. Cannabis Cannabinoid Res, epub ahead
A. Moldavski, H. Wenz, B. Lange, C. Rohleder, F. M. Leweke. (2021) Case Report: Severe adolescent major depressive syndrome turns out to be an unusual case of Anti-NMDA receptor encephalitis. Front Psychiatry 12: 679996.
C. G. Bien, C. Rohleder, J. E. Mueller, C. I. Bien, D. Koethe, F. M. Leweke (2021) Neural autoantibodies in cerebrospinal fluid and serum in clinical high risk for psychosis, first-episode psychosis, and healthy volunteers. Front Psychiatry 12:654602
M.-F. Xiao, S.-E. Roh, J. Zhou, C.-C. Chien, B. P. Lucey, M. T. Craig, L. N. Hayes, J. M. Coughlin, F. M. Leweke, M. Jia, D. Xu, W. Zhou, C. Talbot Jr., D. B. Arnold, M. Staley, C. Jiang, I. M. Reti, A. Sawa, K. A. Pelkey, C. J. McBain, A. Savonenko, P. F. Worley (2021) NPTX2 loss of function and schizophrenia. Sci Adv 7:eabf6935
J. Cooper, S. Han, J. Tomasik, S. Ozcan, N. Rustogi, N. van Beveren, F. M. Leweke, S. Bahn (2019) Multimodel inference for biomarker development: an application to schizophrenia. Transl Psychiatry 9:83
T. Grent-‘t-Jong, J. Gross, J. Goenze, M. Wibral, R. Gajwani, A. Gumley, S. M. Lawrie, M. Schwannauer, F. Schultze-Lutter, D. Koethe, F. M. Leweke, W. Singer, P. J. Uhlhaas (2018) Resting-state gamma-band power alterations in schizophrenia reveal e/i-balance abnormalities across ill-ness-stages. eLife 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 (2018) Evidence of microglial activation following exposure to serum from first-onset drug-naïve schizophrenia patients. Brain Behav Immun 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 (2017) Schizophrenia-risk and urban birth are associated with proteomic changes in neonatal dried blood spots. Transl Psychiatry 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 (2017) Pathogen-mediated NMDA receptor autoimmunity and cellular barrier dysfunction in schizophrenia. Transl Psychiatry 7:e1186
J. M. Coughlin, L. N. Hayes, T. Tanaka, M. Xiao, R. H. Yolken, P. Worley, F. M. Leweke, A. Sawa (2017) Reduced superoxide dismutase-1 (SOD1) in cerebrospinal fluid of patients with early psychosis in association with clinical features. Schizophr Res 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 (2016) Associations of pineal volume, chronotype and symptom severity in adults with attention deficit hyperactivity disorder and healthy controls. Eur Neuropsychopharmacol 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 (2016) Differential melatonin alterations in cerebrospinal fluid and serum of patients with major depressive disorder and bipolar disorder. Comp Psychiatry 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 (2016) Candida albicans exposures, sex specificity and cognitive deficits in schizophrenia and bipolar disorder. npj Schizophr 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 (2016) Pretreatment levels of the fatty acid handling proteins H-FABP and CD36 predict response to olanzapine in recent-onset schizophrenia patients. 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 (2016) Towards a blood-based diagnostic panel for bipolar disorder. Brain Behav Immun 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 (2015) Development of a blood-based molecular biomarker test for identification of schizophrenia prior to disease onset. Transl Psychiatry 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 (2015) Peripheral proteomic profiling of major depressive disorder. Transl Psychiatry 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 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 (2015) The promise of biological markers for treatment response in first-episode psychosis: a systematic review. Schizophr Bull 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 (2015) IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia. Br Behav Immunity 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 (2014) Understanding the role of oleoylethanolamide in obesity: differential association with body mass index and food cue-induced brain activation. JAMA Psychiatry 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 (2014) Inflammatory molecular signature associated with infectious agents in psychosis. Schizophr Bull 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 (2014) Identification of molecular subgroups of schizophrenia patients. Schizophr Bull 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 (2013) Marked reduction of soluble superoxide dis-mutase-1 (SOD1) in cerebrospinal fluid of patients with recent-onset schizophrenia. Mol Psychiatr 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 (2012) Molecular sex differences in human serum. PLoS One 7: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 (2012) Identification of a biological signature for schizophrenia in serum. Mol Psychiatr 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 (2010) Global proteomic profiling reveals altered proteomic signature in schizophrenia serum. Mol Psychiatr 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 (2010) Increased levels of circulating insulin-related peptides in first onset, antipsychotic naïve schizophrenia patients. Mol Psychiatr 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 (2008) Independent protein profiling studies show a decrease in apolipoprotein A1 levels in CSF and peripheral tissues. Mol Psychiatr 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 (2006) Identification of diagnostic biomarkers for first-onset schizophrenia. PLoS Medicine 3:e428
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 3:e327