Molecular Precision Mental Health - Biomarkers for Mental Disorders
The current way of diagnosing most psychiatric disorders relies on clinical examination. However, identifying biological markers can offer an objective method for diagnosis, confirming clinical evaluations and allowing for the monitoring of disease progression and treatment outcomes. To achieve this, our lab (mpmh.me) partners with Sydney Mass Spectrometry at the Charles Perkins Centre of the University of Sydney, where we run a project node called Molecular Precision Mental Health. Our focus is on lipidomic and other omic studies of human and animal tissues to help develop more personalised assessments and treatments for mental health conditions.
We work with international research groups, including the Schizophrenia Center and the Program in Molecular Psychiatry at Johns Hopkins University in Baltimore, MD, USA, led by Prof. Akira Sawa, MD, PhD. Previously, we collaborated with the Cambridge Center for Neuropsychiatric Research (CCNR) at the University of Cambridge, led by Prof. Dr. Sabine Bahn, MD, PhD. Through these partnerships, we have identified fluid biomarker profiles linked to psychiatric disorders.
Our team discovered two biomarker profiles in the cerebrospinal fluid (CSF) of patients experiencing their first episode of schizophrenic psychosis. These profiles laid the groundwork for developing blood-based biomarker tests as part of a European research initiative (SchizDX) 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), the European Commission (SchizDX EU FP7 HEALTH-F4-2009-223427), and a DVCR-Start up grant of the University of Sydney, Australia.
Selected Publications
T. A. Couttas, C. Boost, F. Pahlisch, E. B. Sykorova, J. K. Mueller, B. Jieu, J. E. Leweke, I. Dammann, A. E. Hoffmann, M. Loeffler, O. Grimm, F. Enning, H. Flor, A. Meyer-Lindenberg, D. Koethe, C. Rohleder, F. M. Leweke (2024) Dose-dependent effects of oral cannabidiol and delta-9-tetrahydrocannabinol on serum anandamide and related N-acylethanolamides in healthy volunteers. BMJ Mental Health 27:e301027
B. Jieu, E. B. Sykorova, C. Rohleder, E. Marcolini, A. E. Hoffmann, D. Koethe, F. M. Leweke, T. A. Couttas (2024) Alterations to sphingolipid metabolism from antipsychotic administration in healthy volunteers are restored following the use of cannabidiol. Psychiatry Res 229:116005
M. Allwright, B. Guennewig, A. Hoffmann, C. Rohleder, B. Jieu, L. H. Chung, Y. C. Jiang, B. F. Lemos Wimmer, Y. Qi, A. S. Don, F. M. Leweke, T. A. Couttas (2024) ReTimeML: A retention time predictor that supports the LC-MS/MS analysis of sphingolipids. Sci Rep 14:4375T. 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, 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 8:657-669
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