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Cognitive deficits may identify youth most likely to develop psychosis

Young people at very high risk for psychosis seemed to show cognitive deficits, study findings published in JAMA Psychiatry revealed.

However, those whose high-risk status remitted appeared to recover cognitively, according to the results.

“Meta-analytic evidence indicates that cognitive deficits are present in individuals at ultra-high risk for psychosis. There is a 35% likelihood that the presence of symptoms — functional or cognitive manifestations — in high-risk, care-seeking individuals predates psychosis,” Max Lam, PhD, from the research division at the Institute of Mental Health in Singapore, and colleagues wrote. “However, systematic evidence is scarce for longitudinal cognitive trajectories in individuals at [ultra-high risk] for psychosis.”

The investigators evaluated longitudinal profiles of cognition in young adults at ultra-high risk for psychosis, while also comparing these profiles to those of healthy controls and investigating the link between cognition and functioning using a multiple-group prospective design as part of the Longitudinal Youth At-Risk Study conducted in Singapore.

Every 6 months for 2 years or until conversion to psychosis, researchers performed follow-up assessments to measure neuropsychological, perceptual and social cognitive tasks; they also administered semi-structured interviews and the Structured Clinical Interview for DSM-IV Axis I Disorders. They grouped at-risk individuals as converters or nonconverters and remitters or nonremitters. Specifically, they categorized those at ultra-high risk for psychosis at baseline, but who no longer fulfilled ultra-high-risk criteria at the 2-year time point as remitters and those who met criteria at final assessment or had converted to psychosis as nonremitters.

Overall, investigators evaluated 173 young adults at ultra-high risk for psychosis and 384 healthy controls aged 14 to 29 years, but only 383 healthy controls and 122 people at risk for psychosis remained after 2 years of follow-up. At baseline, cognitive deficits correlated with later psychosis conversion (OR = 1.66; 95% CI, 1.08-2.83; P = .04) and nonremission of ultra-high-risk status (OR = 1.67; 95% CI, 1.09-2.95; P = .04).

Lam and colleagues obtained five cognitive components from principal components analysis – social cognition, attention, verbal fluency, general cognitive function and perception.

In general cognitive function, they found that the longitudinal component structure changed (P = .01). There was also a group-by-time interaction on general cognitive function (P < .001) and perception (P < .001). Further, the investigators reported that the changes in attention (P = .02) and general cognitive function (P = .01) accounted for longitudinal changes in social and occupational functioning.

“Although predominantly a trait, cognitive architecture shows subtle changes over time in nonremitting individuals at [ultra-high risk] for psychosis,” the researchers wrote. “These cognitive architecture changes are associated with functional outcomes and may herald a conversion to psychosis and a cognitive architecture similar to schizophrenia.”

More research in treating cognitive deficits in patients on the schizophrenia spectrum is needed, Philip D. Harvey, PhD, from the Miller School of Medicine, University of Miami, wrote in an accompanying editorial.

“If we want to observe the cognitive worsening that appears to increase risk for persistent symptoms, we will have to look earlier, perhaps before the behavioral changes associated with the prodrome,” he wrote. “Given the challenges in treatment of cognitive deficits and the limited success from pharmacological approaches, the longitudinal correlations in the remitters between cognition and everyday functioning make a strong case, as well, for the real-world clinical relevance of treatments focused on cognitive impairment.” – by Savannah Demko

Disclosure: Lam reports no relevant financial disclosures. Please see the full study for other authors’ relevant financial disclosures. Harvey reports consulting fees or travel reimbursements from Allergan, Akili, Biogen, Boehringer Ingelheim, Forum Pharma, Genentech (Roche Pharma), Intra-Cellular Therapies, Lundbeck Pharma, Minerva Pharma, Otsuka America (Otsuka Digital Health), Sanofi Pharma, Sunovion Pharma, Takeda Pharma, and Teva. He also reports royalties from the Brief Assessment of Cognition in Schizophrenia and grants from Takeda and the Stanley Medical Research Foundation.