Psychosis and Neurodevelopment

Crossroad
Research theme: Cell Biology and Genetics
Clinical pillar: Psychosis and Neurodevelopment

We study genetic variants associated with risk for neurodevelopmental disorders and the molecular and cellular mechanisms leading to psychopathology. We also aim to understand neuro-inflammation in neurodegenerative diseases and nervous system autoimmunity. 

We encompass techniques such as enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), primary cell-culture and immunohistochemistry, we are able to study neuro-immunological mechanisms within myasthenia gravis (MG). In MG, we are investigating the possible use of proteasome inhibitors for targeting autoimmune plasma cells. Long-living plasma cells are resistant against broad-range immune-suppressants and are therefore a major problem in the current treatment of MG and other antibody-mediated autoimmune diseases.

Autoimmune factors

We study autoimmune factors in psychosis, schizophrenia and depression, and improve diagnosis and treatment of psychotic disorder of autoimmune origin. Furthermore, we investigate the role of lipids and their transporters in early inflammatory processes. 

In the area of genetic risk, we work both on rare copy number variants such as 22q11.2 deletion and duplication and 16p11.2 deletion and duplication as part of the NIH-funded “Genes 2 Mental Health” consortium, and also 1q21 deletion and duplication. This work spans the whole range of techniques, from genetics (in collaboration with the Dept. of Clinical Genetics) through cell biology, neuroimaging and detailed clinical phenotyping.  

Unique contributions and highlights

By using thymic patient material from patients undergoing robot thymectomy, and utilising various expertise (pathologists, neurologists, pulmonologists within the MUMC+) we are able to research patient response to available therapies for MG. We do this by distinguishing differences in immune cell population and observing immune cell population variability between patients.

We look at specific neuronal surface antibodies that are known to cause encephalitis, as we aim to expand the clinical spectrum of psychosis potentially caused by autoantibodies. Recently, two of our researchers gained a Kootstra grant, to further elucidate key pathogenic mechanisms previously unknown in muscle specific kinase myasthenia gravis (MuSK MG) and other new antigens of the central nervous system.

MU