The impact, assessment, and longitudinal course of negative symptoms of schizophrenia.

Abstract

The negative symptoms of schizophrenia include impoverished speech, affective blunting, an inability to anticipate pleasure, asociality, and amotivation. Current effective treatment options are limited, which is a significant issue given their strong association to functional impairment. The primary aims of this thesis are to explore areas which may inform the design of clinical trials addressing these symptoms, build upon recent advances in negative symptom assessment, and further understand the impact of negative symptoms on outcomes. A meta-analysis examining the longitudinal course of negative symptoms demonstrated a consistent reduction in negative symptoms over the study period in all treatment conditions examined, including in studies which adopted different eligibility criteria to minimise the presence of secondary negative symptoms. A comparison of different eligibility criteria revealed that whilst these criteria reduce the association between negative and depressive symptoms, their association to positive symptoms remains largely unaffected, and can substantially reduce the proportion of available participants. Given existing negative symptom assessment tools have been identified as a significant barrier in the development of new treatments, a comparison of assessment methods was performed. Results revealed the Clinical Assessment Interview for Negative Symptoms to be a more sensitive instrument, and a better predictor of functional impairments, relative to the negative subscale of the Positive and Negative Syndrome Scale. Findings described here also demonstrate that the link between negative symptoms and subjective quality of life may be stronger than previously assumed, relating exclusively to experiential deficits. Finally, manic and positive symptoms, rather than negative symptoms, were found to be associated with inpatient treatment appraisal, an important factor in treatment outcomes. Overall, this thesis describes key findings which demonstrate the importance of the appropriate assessment of negative symptoms of schizophrenia, shine new light on symptom progression over time, and highlight a need to further refine clinical trial inclusion criteria