From The Quarterly, May 2016

The onset of schizophrenia and other psychotic disorders is preceded by a period during which individuals begin to experience some psychotic symptoms—but these symptoms can also occur in people who will never develop a psychotic disorder. Thus, researchers are still trying to develop reliable methods to determine who is most in need of interventions that prevent or delay the onset of these disorders.

For more than two decades, individuals whose symptoms and genetic profile match any of three sets of criteria have been considered at “ultra-high risk” for psychosis; about 30 percent of the individuals in this group develop a psychotic disorder within two years. Now, an international team led by Paolo Fusar-Poli, M.D., Ph.D., at King’s College London, whose 2014 Young Investigator helped fund the work, has found that the risk of psychosis varies significantly among three different groups of ultra-high risk individuals. Recognizing the distinctions between the three groups will be important for the design of future research studies, the scientists say, and could help researchers identify biomarkers that can be used to predict which at-risk individuals will develop psychotic disorders.

The scientific team that conducted the analysis included 1999 and 2002 Young Investigator Cheryl Corcoran, M.D.; 1998 Distinguished Investigator and 2015 Lieber Prize winner Patrick D. McGorry, M.D., Ph.D.; 2010 Distinguished Investigator Philip K. McGuire, M.D., Ph.D.; 2015 Independent Investigator, 2008 Young Investigator, and 2015 Sidney R. Baer Jr. Prize winner Barnaby Nelson, Ph.D.; 2005 Distinguished Investigator and 1998 Independent Investigator Scott W. Woods, M.D.; and 2003 Independent Investigator Alison R. Yung, M.D.

To be considered ultra-high risk for a psychotic disorder, an individual must have one of the following: attenuated or weak psychotic symptoms (APS), brief limited intermittent psychotic symptoms (BLIPS), or genetic risk combined with functional deterioration (GRD). Psychosis symptoms can include feeling paranoid, having false ideas about what is taking place or who one is, and seeing, hearing, or feeling things that are not there. Using data from 33 prior studies on psychosis risk, which together included more than 4,000 individuals, the team of scientists compared how many patients within each group developed a psychotic disorder within six, 12, 24, and 36 months, as well as within follow- up periods of four years or more.

The majority of high-risk individuals included in the analysis—85 percent—fell into the APS category. Another 10 percent had experienced BLIPS and five percent were classified as high-risk based on GRD.

The team’s analysis, published in JAMA Psychiatry on December 30, 2015 showed that after the first year, individuals who had been considered at ultra-high risk due to brief limited intermittent psychotic symptoms were significantly more likely to develop a psychotic disorder than those who had experienced attenuated psychotic symptoms. At two years, those with BLIPS were about twice as likely to have developed psychosis as those with APS.

Those with genetic risk and deterioration, on the other hand, were no more likely to develop a psychotic disorder than individuals in a control group, who had not been classified as at high risk for psychosis.