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Neuropsychological and biological mechanisms of checking in OCD and clozapine induced Schizo-OCS



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Biria, Marjan 


The introductory Chapter 1 reviewed several possible explanations of compulsive behaviour as manifested especially in Obsessive Compulsive Disorder (OCD), and schizophrenia, following treatment with the second generation antipsychotic medication clozapine. Particular focus is placed on compulsive checking behaviours and their relationship to current theories of compulsivity based on the hypothesis of imbalance between the goal-directed and habit systems and aberrant prediction-error learning. Chapter 2 describes experimental attempts in this thesis to measure human checking behaviour in the laboratory. Initially, a previously published test of checking was employed which however failed to show significant increases in OCD. I then designed a new testing procedure to measure checking, based on perceptual decision-making under a time constraint. This was administered together with other cognitive tests to patients with OCD, clozapine treated schizophrenia patients without and with obsessive compulsive symptoms, and a healthy volunteer group. In general, there were no major differences compared to controls, although patients with schizophrenia performed worse. In a second study, contingency degradation learning and checking were measured using a second variant of the task in which there was no time constraint. However, significant increases in checking behaviour were shown in another group of OCD patients compared with healthy volunteers. In Chapter 3, after a review of previous findings in OCD using the Magnetic Resonance Spectroscopy (MRS) technique at 7T, the same participants employed in the last checking study, were subjected to MRS scans to measure GABA, Glutamate (Glu), Glutamine (Gln), and NAA in three areas of brain including the Anterior Cingulate Cortex (ACC), Supplementary Motor Area (SMA) and the Visual Cortex. The most important findings were in the ACC, where significantly higher levels of Glu and Gln and lower levels of GABA and GABA:Glu ratio were found in OCD patients compared to the healthy group. In Chapter 4, the relationship between the behavioural results from chapter 2 and the neurometabolites measured with MRS in our OCD and healthy participants in chapter 3 was examined. The major findings were: 1) Higher ACC GABA/Glu ratio was related to superior accuracy of decision-making as well as increased checking on the checking task in OCD patients. 2) Checking was negatively correlated with SMA Glu in the healthy group but not in OCD. Moreover, in a test of goal directed behaviour and habit learning based on contingency degradation, a positive relationship was evident between performance and the ACC GABA/Glu ratios in patients for full degradation of the task contingencies. A similar positive relationship was observed for healthy volunteers for GABA/Glu ratios in SMA for partial degradation of the contingencies. Chapter 5 discusses neuropsychological interpretations of our findings in relation to the symptomatology of OCD and schizophrenia, together with their implications for understanding the role of the anterior cingulate cortex in decision-making and compulsive behaviour.





Robbins, Trevor W


OCD, Schizophrenia, Schizo-OCS, Magnetic Resonance Spectroscopy (7-Tesla), Checking behaviour, GABA/Glu ratio, Anterior Cingulate Cortex, Supplementory Motor Area


Doctor of Philosophy (PhD)

Awarding Institution

University of Cambridge
Wellcome Trust (202432/Z/16/Z)