Lotje D De Witte, MD, PhD
img_Lotje D De Witte
ASSISTANT CLINICAL PROFESSOR | Psychiatry
Auto-antibodies
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.
Microglia
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.
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.

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Dr. De Witte did not report having any of the following types of financial relationships with industry and other outside entities during 2023 and/or 2024: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.

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