Some Ultra-High Risk Subgroups Are at Higher Risk of Psychosis Than Others

Since the mid-1990s, clinicians have classified individuals as being at ultra-high risk (UHR) for psychosis if they met at least one of three criteria: the presence of attenuated psychotic symptoms (APS), the presence of positive symptoms at full psychotic intensity for brief, limited time points (known as BLIPS), and/or a combination of genetic risk or schizotypal personality disorder accompanied by functional decline (known as genetic risk and decline syndrome [GRD]). However, the risk of psychosis of these different groups has remained unknown.

A meta-analysis published today in JAMA Psychiatry now offers evidence that some ultra-high risk subgroups carry a higher risk of psychosis than others.

Paolo Fusar-Poli, M.D., Ph.D., of King’s College and colleagues analyzed the outcomes of 33 independent studies, including over 4,000 UHR individuals monitored for psychosis progression. The researchers found that people with BLIPS had the highest risk of conversion to psychosis (39% after 24 months), followed by APS (19%) and GRD (3%). In addition, patients who had both APS and GRD had a similar risk of conversion to psychosis as those with only APS across all time points studied—suggesting GRD may not be a valid component of the UHR profile.

“There is meta-analytical evidence of heterogeneous levels of risk of psychosis in [clinical high risk] samples,” the study authors wrote. “Authors of future CHR studies are advised to stratify their findings across these different subgroups.”

In a related editorial, Barbara Cornblatt, Ph.D., M.B.A, and Ricardo Carrión, Ph.D., of the Zucker Hillside Hospital, North Shore–Long Island Jewish Health System, describe the clinical and research implications of the study. “The findings of Fusar-Poli et al. challenge the way prodromal identifications have been made for the past 20 years and will undoubtedly have a positive effect on high-risk research and future criterion modifications,” they wrote.

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