Youth at High Risk for Psychosis: What Happens to Those Who Don’t Become Psychotic?

What does the long-term trajectory look like for young people at high risk for developing psychosis and schizophrenia?

In tandem with the search for biomarkers that might more clearly delineate those who will experience psychosis and those with a more benign course, understanding the trajectory of at-risk individuals is the subject of at least two major projects at the National Institute of Mental Health and numerous research endeavors worldwide.

Identifying those young people who may go on to develop full-blown psychosis (or “convert”) and are most urgently in need of intervention is, naturally, of intense interest to researchers and clinicians. But youth at very high risk who are not destined to experience psychosis are no less important: What variables—genetic, familial, neurobiological, and/or experiential—distinguish them from those who convert to psychosis?

Moreover, while there is a subset of high-risk individuals who appear to remit, most young people who have met high risk criteria continue to experience significant mental illness, and many still meet high-risk criteria years later.

A report in the February Schizophrenia Bulletin found that more than half of individuals at “ultrahigh risk” (UHR) of psychosis who did not convert to psychosis over a six- to 12-year period continued to have a persistent nonpsychotic mental disorder six to 12 years later, and a third also developed a nonpsychotic mental disorder. More than a quarter still met ultrahigh-risk criteria. Ultrahigh risk refers to youth or young adults who experience a range of brief, intermittent psychotic symptoms and/or subthreshold psychotic experiences, putting them at greatly increased odds of developing frank psychosis or schizophrenia. UHR status was determined using the Comprehensive Assessment of At-Risk Mental States (CAARMS).

The researchers evaluated 102 young people (62% female) enrolled in the Personal Assessment and Evaluation Clinic, a specialized clinic for high-risk youth at Orygen, a youth mental health center in Melbourne, Australia. All participants were between 15 and 30 years of age at baseline and met the criteria for UHR but had not converted to full-blown psychosis at a follow-up assessment six to 12 years after their baseline assessment.

Overall, 54% of participants had a nonpsychotic disorder that persisted from baseline to follow-up, and 35% were diagnosed with a new nonpsychotic disorder during the follow-up period. The disorder that was the most persistent over time was mood disorder. Additionally, of the 84 patients for whom data were available on UHR status at follow-up, 29% continued to meet UHR criteria and were more likely to have a co-occurring mental disorder.

Kristin Cadenhead, M.D., is a professor of psychiatry at the University of California, San Diego, and director of the university’s Early Psychosis Treatment Program. She reviewed the report for Psychiatric News and said the relatively long follow-up period in the Australian study is an important contribution; most previous studies have had follow-up periods of two to three years.

“These results confirm that there is a large percentage of at-risk people who remain symptomatic more than six years after baseline and still have a high rate of comorbid psychiatric diagnoses, predominantly depression and anxiety,” she told Psychiatric News. “And those who have comorbid psychiatric diagnoses are typically functioning more poorly than those who are in remission.”

She said the majority of high-risk patients are help-seeking individuals in need of treatment regardless of whether they convert to psychosis. “Given the level of comorbidity, many [of those who do not convert] are often receiving some level of treatment,” she said. “Cognitive-behavioral therapy has the best evidence, and it is effective as a broad-spectrum treatment for depression, anxiety, and more generally the stress of being a teenager.”