Molecular mechanisms in Tourette and obsessive-compulsive disorders

Monday 12 June 2023, 4:30 pm
PhD student
J.M. Widomska MSc.
prof. dr. J.K. Buitelaar
dr. J.C. Glennon, dr. G.J.V. Poelmans

Through animal model and human studies, this thesis aimed at identifying the molecular mechanisms involved in Tourette’s disorder (TD) and obsessive-compulsive disorder (OCD) and finding novel treatment targets. First, TD-/OCD-like behaviors in the PANDAS mouse model were modulated by estradiol and estradiol-regulated molecules, and were reduced by neonatal stress. In a rat model of abnormal involuntary movements (AIMs) – which resemble the tics in TD – the drug Riluzole counteracted AIMs by reducing the activity of the transcription factor CREB1. Further, the molecular landscape of TD – built based on the human omics data – implicated several pathways and processes in the disease, including cAMP and endocannabinoid signaling, multiple metabolic pathways and synaptic functioning. The landscape also yielded clues towards novel potential treatment targets, i.e., FLT3, NAALAD2, CX3CL1-CX3CR1, OPRM1 and HRH2. Lastly, based on genetic data sets, OCD, OCD-like symptoms in the general population and insulin signaling were found to show partial genetic overlap.

Joanna Widomska (1988) obtained her M.Sc. in Biotechnology at the University of Life Sciences in Poznań, Poland in 2012, after which she worked at the University of Liverpool, UK. In 2014, she started PhD research at the Radboudumc, as part of the ‘TS-EUROTRAIN’ project. Since 2017, she has been working at Drug Target ID, a spin-out of Radboud University.