PhD defence J.O.Z. (Job) de Jong

The focus of this thesis is the role of rare genetic variation in the etiology of psychiatric disorders. Rare genetic variants typically confer a high risk for illness. The study of rare genetic variation can inform us on psychiatric disease mechanisms. It is important to uncover psychiatric disease mechanisms as these can lead to the development of new treatments. The field of psychiatry has not seen any genuine, new pharmacologic treatments since the introduction of the major classes of drugs in the second half of the previous century, leaving large groups of patients with impairing, chronic, treatment-resistant illness. Using genetically isolated populations is advantageous for the study of rare genetic variation.   
In one study we investigated a large pedigree from the genetically isolated Old Order Mennonite population and identified a rare genetic variant that increases risk for major depression by three-fold. Insertion of this human gene in mice introduced aberrant emotional behavior that could be rescued by antidepressant treatment. 
In another study we investigated patients from the genetically isolated Old Order Amish population with a genetic syndrome consisting of autism spectrum disorder, epilepsy and intellectual disability and signs of brain overgrowth (increased head circumference and increased gray matter volume). In order to uncover the mechanism of this psychiatric syndrome, we generated so called lab-grown brain organoids and found that we could reproduce several aspects of this brain-overgrowth in our model system, thereby creating a human model system that can be used to search for novel treatments.

The public defence will take place at the Prof. Andries Queridoroom, 3rd floor Education Center, location Erasmus MC. The ceremony will begin exactly at 15.30 PM. In light of the solemn nature of the ceremony, we recommend that you do not take children under the age of 6 to the first part of the ceremony.