Dr. de Witte is a psychiatrist with a background in preclinical research in the fields of virology and immunology. She studied Medicine at the University of Amsterdam, the Netherlands and performed a Ph.D. at the department of cell biology and immunology at the VU medical center in Amsterdam and a postdoc at the department of virology at the Erasmus MC, Rotterdam, the Netherlands, where she was extensively trained in the concepts and techniques involved in immunology, cell biology and virology. She investigated the role of Langerhans cells and other myeloid cell types in viral infections. She set up various cellular models in the lab, including the isolation of primary Langerhans cells. Dr. de Witte graduated cum laude for her Ph.D. and her research projects have been published in high impact journals including Nature Medicine, the Journal of Clinical Investigation, PLOS pathogens and PNAS.
After graduating cum laude for her M.D., Dr.de Witte decided to specialize in psychiatry. She was not only attracted to this field from a clinical point of view but also devoted to use her experience in immunology to start to unravel how the immune system plays a role in psychotic disorders. In parallel to her residencies in psychiatry, she therefore started her own research group at the Brain Center Rudolf Magnus in Utrecht, the Netherlands. She investigated the prevalence and role of neuronal auto-antibodies and neurotropic pathogens in psychotic disorders. In addition, she set up several human microglia models, including the isolation of these cells from post-mortem brain tissue, generating them from induced pluripotent stems cells and monocytes. This has resulted in a novel and distinctive research line studying the phenotype and function of microglia in psychotic disorders.
Education and Training
2008 PhD, Department of Molecular Celbiology & Immunology, VU Medical Center
Amsterdam, The Netherlands
2010 MD, School of Medicine, VU Medical Center
Amsterdam, The Netherlands
2008-2010 Postdoc, Department of Virology, Erasmus MC
Rotterdam, The Netherlands
2011-2016 Residency Psychiatry, UMC Utrecht
Utrecht, The Netherlands
2011-2017 Postdoc Translational Neuroscience,
Utrecht, The Netherlands
2016-2017 Psychiatrist Department of Psychiatry, University Medical Center
Utrecht, The Netherlands
2017-present Assistant Professor, Department of Psychiatry, Icahn School of Medicine at Mount Sinai,
New York, USA
The role of the immune system in psychiatric disorders
An association between the immune system and psychiatric disorders, such as schizophrenia, bipolar disorder and autism, is becoming more and more evident. Targeting the immune system is therefore one of the major focuses for finding novel drug targets. However, it is still largely unknown how immune processes are involved in these diseases at the molecular level.
Microglia cells are the resident immune cells of the brain. From animal studies it is known that microglia are not only involved in initiating and controlling inflammation in the central nervous system (CNS), but that they are also crucial for neurodevelopment and neuronal functioning in adulthood. In her lab, Dr. de Witte studies whether one of these functions is affected in psychiatric disorders. She has set up several human microglia models, including the isolation of these cells from post-mortem brain tissue, generating them from induced pluripotent stems cells and monocytes. Using these models she compares microglia from patients and controls at the phenotypic and functional level. In addition, she studies whether specific genetic risk factors for neurodevelopmental disorders alter microglia functioning.
Antibodies that bind to synaptic proteins can cause autoimmune encephalitis and this can lead to prominent psychiatric symptoms. A clear example is anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, which is caused by auto-antibodies to one of the subunits of the NMDA receptor. Dr. de Witte studies whether subgroups of patients with psychiatric disorders may have an underlying autoimmune disease caused by neuronal auto-antibodies. Her studies on blood samples of patients with schizophrenia or bipolar disorders indicate that the presence of these auto-antibodies is very rare. She is now involved in validating these findings in cerebrospinal fluid.
van Mierlo HC, Wichers CG, He Y, Sneeboer MA, Radstake TR, Kahn RS, Broen JC, de Witte LD. Telomere quantification in frontal and temporal brain tissue of patients with schizophrenia. Journal of psychiatric research 2017 Sep; 95.
van der Doef TF, de Witte LD, Sutterland AL, Jobse E, Yaqub M, Boellaard R, de Haan L, Eriksson J, Lammertsma AA, Kahn RS, van Berckel BN. In vivo (R)-[(11)C]PK11195 PET imaging of 18kDa translocator protein in recent onset psychosis. NPJ schizophrenia 2016; 2.
Melief J, Sneeboer MA, Litjens M, Ormel PR, Palmen SJ, Huitinga I, Kahn RS, Hol EM, de Witte LD. Characterizing primary human microglia: A comparative study with myeloid subsets and culture models. Glia 2016 Nov; 64(11).
van Mierlo HC, van Coevorden-Hameete MH, Munting LP, de Graaff E, de Witte L. No evidence for the presence of neuronal surface autoantibodies in plasma of patients with schizophrenia. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 2015 Dec; 25(12).
van Mierlo HC, Titulaer MJ, Kromkamp M, van de Kraats R, van Veelen NM, Palmen SJ, Kahn RS, de Witte LD. Early recognition of anti-N-methyl-D-aspartate receptor encephalitis in psychiatric patients. Acta psychiatrica Scandinavica 2015 Oct; 132(4).
de Witte LD, van Mierlo HC, Litjens M, Klein HC, Bahn S, Osterhaus AD. The association between antibodies to neurotropic pathogens and schizophrenia: a case-control study. NPJ schizophrenia 2015; 1.
van Mierlo HC, de Witte L, Derksen RH, Otten HG. The prevalence of antinuclear antibodies in patients with schizophrenia spectrum disorders: results from a large cohort study. NPJ schizophrenia 2015; 1.
de Witte LD, Hoffmann C, van Mierlo HC, Titulaer MJ, Kahn RS, Martinez-Martinez P. Absence of N-Methyl-D-Aspartate Receptor IgG Autoantibodies in Schizophrenia: The Importance of Cross-Validation Studies. JAMA psychiatry 2015 Jul; 72(7).
de Witte L, Tomasik J, Schwarz E, Guest PC, Rahmoune H, Kahn RS, Bahn S. Cytokine alterations in first-episode schizophrenia patients before and after antipsychotic treatment. Schizophrenia research 2014 Apr; 154(1-3).
de Witte L, Nabatov A, Pion M, Fluitsma D, de Jong MA, de Gruijl T, Piguet V, van Kooyk Y, Geijtenbeek TB. Langerin is a natural barrier to HIV-1 transmission by Langerhans cells. Nature medicine 2007 Mar; 13(3).
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Dr. De Witte has not yet completed reporting of Industry relationships.
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