Melbourne School of Psychological Sciences - Theses
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ItemWhy transition is not the whole story: neurocognitive function and risk for psychosis( 2010)“Ultra-high risk” (UHR) refers to individuals thought to be in the prodromal phase of psychotic disorder. The neurobiological mechanisms underlying progression from UHR to frank psychosis remains unclear, although neurocognition has been shown to be a promising endophenotypic marker. The aim of this project was to investigate baseline neurocognitive markers of transition to psychosis and poor functional outcome in a cohort identified as UHR between two and 14 years prior. Extensive tracking was used to trace all individuals who participated in research at the PACE Clinic in Melbourne from 1994-2005 (N = 416). Seventy five percent of the sample was assessed by interview. Transition status was established for all 416 participants. There were three main aspects to this research project: the examination of transition to psychosis, poor functional outcome and change in performance over time in relation to neurocognitive function. This study is the longest follow-up of any UHR sample to date, with a mean follow-up period of 7.52 years (SD 3.26). It was demonstrated that 29.3% of the sample transitioned to psychosis and that transition occurred up to five years and more after identification as UHR. When all baseline neurocognitive scores were modelled together, none significantly predicted transition. Conversely, lower functioning and psychotic symptom scores significantly predicting the development of frank psychosis. Of the individuals who experienced poor functional outcome (defined by low scores on the Quality of Life Scale and Social and Occupational Functioning Assessment Scale), less than two thirds of them had ever experienced a frank psychotic episode and less than one third had schizophrenia. The poor outcome group showed impaired neurocognitive performance at baseline, particularly on the task of logical memory. Poor performance on this task was still the strongest predictor of later poor functioning when modelled with baseline functioning and symptom scores. This model correctly classified 75% of poor outcome cases. Very poor Verbal IQ and verbal learning and memory at baseline significantly increased the odds of poor functioning at follow-up. In general, the neurocognitive performance of the cohort improved over the follow-up period. There were no significant interactions of transition group by time, indicating that individuals who transitioned did not show a significant reduction in neurocognition relative to those who did not. However, interactions of functional outcome group by time were significant on Verbal and Full-scale IQ, and a task of attention and processing speed. The poor outcome group showed decrements in performance on these measures, while the good outcome group improved over time. The current results indicate a need to shift the traditional notion of outcome in UHR investigation. It may no longer be sufficient to focus only on transition to psychosis because there is a group of individuals who never transition to threshold level psychosis, but continue to demonstrate very poor social and occupational functioning. The results also bring into question the validity of comparing individuals who transition to psychosis with those who do not in the search for biomarkers and endophenotypes for schizophrenia.