Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Science

Program

Neuroscience

Supervisor

Palaniyappan, Lena

Affiliation

University of Western Ontario, McGill University

2nd Supervisor

Muller, Lyle

Co-Supervisor

Abstract

The considerable variation in the spatial distribution of cortical thickness changes has been used to parse heterogeneity in schizophrenia. We aimed to recover a ‘cortical impoverishment’ subgroup with widespread cortical thinning. We applied hierarchical cluster analysis to cortical thickness data of three datasets in different stages of psychosis and studied the cognitive, functional, neurochemical, language and symptom profiles of the observed subgroups. Our consensus-based clustering procedure consistently produced a subgroup characterized by significantly lower cortical thickness. This ‘cortical impoverishment’ subgroup was associated with a higher symptom burden in a clinically stable sample and higher glutamate levels with language impairments in the first-episode sample. Overall, cortical thinning is more prevalent among patients, especially those with glutamate excess and speech dysfunctions in the early stages and higher residual symptom burden at later stages.

Summary for Lay Audience

Schizophrenia is one of the most disabling and chronic mental illnesses. Patients, despite having the same diagnosis, can have very different clinical histories, symptom profiles and treatment responses. This has posed challenges for clinicians to provide personalized treatment plans. Therefore, researchers have made efforts to classify patients into subtypes, so that this illness can be better understood and characterized. The current thesis pursued this line of effort and aimed to find patient subtypes based on brain features. Compared to clinical features that could be subjective and fluctuate over time, brain features are a more stable and objective indicator of cognitive and mental health status. For example, cortical thickness, the thickness of the outer layer of the brain, is found to be abnormal in some patients with schizophrenia. It may be an important first step to differentiate patients with a healthy cortical thickness profile from patients with lower cortical thickness, because these two patient subgroups may represent distinct origins of the same illness. Cluster analysis is a useful mathematical tool to identify patient subgroup(s) with different brain profiles. It can assign patients with similar profiles to the same group, and then we can determine when the subgroups are too distant to belong to one. In our study, we found that there were two subgroups of patients in both chronic and first-episode schizophrenia. One subgroup showed no difference in cortical thickness patterns from healthy controls, while the other displayed cortical thinning in multiple regions of the brain. In chronic and stable schizophrenia, patients with extensive cortical thinning experienced a higher residual symptom burden. In first-episode schizophrenia, this subgroup showed an abnormal level of glutamate. Glutamate is a molecule in our brain that sends signals to excite brain cells. This subgroup also had impaired speech production such as simplicity in the structures of the sentences, and reduced cohesion between sentences. To conclude, a patient subgroup with widespread cortical thinning may represent a distinct subtype which is stable across various stages of schizophrenia with dysregulated neurochemical levels and abnormal language production. It may be important to customize mental health care strategies for this subgroup of patients.

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