Commentary

Over the past 25 years, significant advances have been made in establishing a reliable ultra high risk (UHR) syndrome that predicts the onset of psychotic disorders. This has ushered in the exciting possibility that one can prevent psychosis with early, targeted interventions. To achieve this possibility, researchers are focusing on reliably identifying clinical predictors of risk, which clinicians can use to guide preemptive treatments.

Nelson and colleagues investigated predictors of transition to psychosis in the first long-term follow-up study of UHR patients. The rate of conversion results were consistent with prior studies¹, suggesting that the UHR criteria continues to be a valid and reliable predictor of imminent psychosis onset. The most robust clinical predictors included longer duration of attenuated psychotic symptoms (>738 days) and poor global functioning (GAF <44), which led to a risk of 72% of developing psychosis within five years. While this risk profile might represent individuals inevitably on the path to developing psychosis, it is possible that a focused strategy of aggressively treating global functioning impairments and comorbid mood and anxiety symptoms could protect against transition to psychosis. Few interventions in UHR samples have focused on this approach. Instead, treatment strategies target attenuated psychotic symptoms, which yield limited success at preventing psychosis in UHR patients.

In addition to developing targeted treatment strategies for preventing psychosis, this study highlights the importance of learning more about influences on functional impairment in this population. In schizophrenia, we know cognitive deficits and negative symptoms are the primary drivers of functional impairment, but less is known about the role of comorbidities affecting functional outcomes in UHR patients. In clinical practice, targets for treatment should expand to treating mood and anxiety symptoms, rather than only on attenuated psychotic symptoms. The clinical implications of this paper’s findings are limited by the narrow scope of examining only psychosis as an outcome. It is unclear, for instance, why some individuals who are identified as at-risk do not develop psychosis. While this might have been out of scope of the current paper, the findings could have had greater clinical relevance if it examined predictive factors of resilience from an at-risk state.