PhDThe 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 criteri
