Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Neuroscience

Supervisor

Palaniyappan, Lena

2nd Supervisor

Finger, Elizabeth

Co-Supervisor

Abstract

A significant cause of disease related burden in schizophrenia relates to reductions in social and occupational functioning. Thus, understanding the variables that are associated with good versus poor functional prognosis is key to improving overall patient outcomes. This dissertation assessed the associations between baseline variables and later occupational and social deficits in the first year of treatment. In chapter 1, we used automated linguistic analysis software programs to determine if elements of speech production were aberrant in patients versus healthy controls. These features were then entered into a prototypical constraint-based algorithm to identify any dependencies with vocational inactivity (NEET), or scores on the Social and Occupational Functioning Assessment Scale (SOFAS). Only reduced speech (lower total words spoken) explained worsened occupational and community functioning. In chapter 2 we assessed whether baseline cortical thickness or local gyrification index (LGI) were associated with baseline clinical severity and later social and vocational status. We identified increased gyrification in frontal and parietal regions to be associated with increased symptom burden at baseline, as well as with a higher status of vocational inactivity following treatment. Finally, we assessed whether central anti-oxidant tone measured in-vivo was associated with better social and vocational outcomes, revealing an association between higher glutathione levels at baseline and improved functional outcomes in the first year of treatment. By elucidating these mechanisms within early psychosis samples, clinicians may be able to augment standard treatment paradigms to improve outcomes among patients at risk of poor treatment response.

Summary for Lay Audience

In his Labor Day address in 1907, Theodore Roosevelt proclaimed “Far and away the best prize that life offers is the chance to work hard at work worth doing”. This simple quote captures the value that meaningful work has in one’s life. However, for the roughly 1 in 100 individuals who develop schizophrenia or related psychoses, the ability to find and maintain meaningful employment is critically impacted. Studies suggest that only 10-20 percent of schizophrenia patients are able to obtain and maintain employment throughout their lives. This dissertation aims to identify early predictors of poor vocational outcomes in a sample of drug-naïve first episode psychosis patients, with the hope that at-risk patients can be identified, and provided with early support to improve long term community functioning. To this end, we have recruited a group of patients who were recently diagnosed with their first episode of psychosis and have not yet undergone a course of treatment with antipsychotics. We assessed three classes of variables (speech variables, brain anatomy, and brain metabolite concentrations) to determine if they were linked to poor vocational and community functioning after 6-12 months of treatment.

Our findings indicate that reduced speech production (fewer words spoken during 3 minute interview), increased cortical (brain) folding, and lower levels of glutathione (the brains primary antioxidant) at baseline were associated with vocational inactivity and worse social functioning in the first year of treatment in an early intervention program. Among schizophrenia samples, a significant portion of clinical and functional recovery occurs within the first year of treatment, and once a chronic course of illness is established it becomes increasingly difficult to return to a pre-morbid level of functioning. Thus, the identification of these risk factors for poor functional prognosis is critical as this may allow clinicians to provide additional therapies to at risk patients before a debilitating course of illness is established.

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