Understanding the neurobiological mechanisms of clozapine-induced Obsessive Compulsive Symptoms in schizophrenia and its treatment

Mental Health Research PhD Scholarship 2018: Dept of Psychology, Downing St, University of Cambridge

Supervisor: Professor Trevor Robbins


The use of Second Generation Antipsychotic drugs, particularly clozapine, has represented a considerable advance in treating schizophrenia, especially in otherwise treatment resistant patients. However, this drug is associated with negative consequences, including a distressing syndrome of obsessive-compulsive symptoms (OCS) which is little understood. Although the dopamine blocking drug aripiprazole appears to reduce clozapine-associated OCS, why this should work to counter the syndrome is not known. This drug may improve OCS by reducing the activity of a part of the frontal lobes of the brain called the anterior cingulate cortex which appears to be over-activated in OCD patients and is implicated in checking behaviour commonly observed in OCS. We plan to better characterise the underlying psychological and brain basis of clozapine-induced OCS and its remediation by aripiprazole. Our ultimate aim would be to provide a predictor or biomarker using EEG methods with behaviour of risk of OCS in early episode patients with schizophrenia to be treated with clozapine.

Research Student: Marjan Biria

Bachelor of Clinical Psychology Vrije Universiteit Brussel (VUB), Brussel Belgium. Feb. 2009-Jun. 2013
Thesis: Effects of rumination and worry on working memory performance.

Master of Neuroscience.University of Geneva, Geneva Switzerland. Feb. 2014-Sep. 2015
Thesis: Investigating the EEG biomarkers of schizophrenia in a population with 22q11.2 Deletion syndrome.

Honours and Awards
Highest GPA of the class Master of Neuroscience, University of Geneva, Geneva Switzerland. Feb. 2014-Sep. 2015
First student with the maximum grade of 6 for Statistics and Probability course Feb. 2014-Sep. 2015
Master of Neuroscience, University of Geneva, Geneva Switzerland.
Vahabzadeh Scholarship Sep. 2014-Sep. 2015

Research experience
Research assistant at FBM lab (10% teaching). University of Geneva, Switzerland. Nov.2015-Mar.2017
Intern at Functional Brain Mapping(FBM) lab University of Geneva, Switzerland. Jan.-Sep. 2015
Research: Conducting research about Visual processing in individuals with 22q11-Deletion Syndrome as a model for Schizophrenia.

Intern at Bavelier lab University of Geneva, Switzerland. July-Dec. 2014
Research: Conducting research about the positive and negative effects of video games on behaviour, attention and vision.

Intern at Geneva University Hospitals (HUG): EEG and Epilepsy Unit University of Geneva, Switzerland Feb.-June 2014
Research: Mapping of the language regions in epilepsy patients.

Faculty of Psychology, VUB, Belgium. 2012-2013
Research: Sleep study using polysomnography, preceded and followed by clinical and neuropsychological tests to examine cognitive functioning after a bad or good quality of sleep.

Faculty of Psychology, VUB, Belgium.2012-2013
Research: Cognitive and psychological scale interviews and providing clinical feedback.

Faculty of Psychology, VUB, Belgium. 2011-2012
Research: Performing different clinical and neurological battery tests and diagnosis.

Faculty of Psychology, VUB, Belgium. 2010-2011
Research: Using different Cognitive Assessment Batteries to evaluate the cognitive development in infants.

Teaching experience
Teaching EEG recording and data analysis. University of Geneva, Switzerland. 2015-2016
Statistics private lessons. Geneva, Switzerland. 2014-2015

Submitted for publication after a first round of revision: "Visual processing deficits in 22q11.2Deletion Syndrome "
Authors: Marjan Biria, MSc; Miralena I Tomescu, PhD; Anna Custo, PhD; Lucia M Cantonas, MSc; Kun-Wei Song, B.A., M.D.; Maude Schneider, PhD; Micah M. Murray, PhD, Professor; Stephan Eliez, MD, PhD, Professor; Christoph M Michel, PhD.

Start Date: September 2017

Study Aims: 

Clozapine is one of the most effective second generation anti-psychotics (SGA) in the treatment of schizophrenia but is commonly associated with Obsessive Compulsive Symptoms (OCS), resulting in a negative prognosis [1]. However, the underlying neural and psychological basis of this syndrome and its possible treatment is not understood [2]. This project proposes a multimodal approach combining cognitive, EEG, magnetic resonance imaging and psychopharmacological methods to characterise this important syndrome, define its possible predictors/biomarkers, and test the possible mechanisms of its main treatment via the dopamine D2-receptor agent aripiprazole.