Longitudinal Cognitive Changes in Young Individuals at Ultrahigh Risk for Psychosis
Authors: Max Lam, Jimmy Lee, Attilio Rapisarda, Yuen Mei See, Zixu Yang, Sara-Ann Lee, Nur Amirah Abdul-Rashid, Michael Kraus, Mythily Subramaniam, Siow-Ann Chong, Richard S. E. Keefe
Journal: JAMA Psychiatry (2018)

<h3>Importance</h3> Cognitive deficits are a key feature of risk for psychosis. Longitudinal changes in cognitive architecture may be associated with the social and occupational functioning in young people. <h3>Objectives</h3> To examine longitudinal profiles of cognition in individuals at ultrahigh risk (UHR) for psychosis, compared with healthy controls, and to investigate the association of cognition with functioning. <h3>Design, Setting, and Participants</h3> This study has a multiple-group prospective design completed in 24 months and was conducted from January 1, 2009, to November 11, 2012, as part of the Longitudinal Youth at-Risk Study conducted in Singapore. Participants either were recruited from psychiatric outpatient clinics, educational institutions, and community mental health agencies or self-referred. Follow-up assessments were performed every 6 months for 2 years or until conversion to psychosis. Individuals with medical causes for psychosis, current illicit substance use, or color blindness were excluded. Data analysis was conducted from June 2014 to May 2018. <h3>Main Outcomes and Measures</h3> Neuropsychological, perceptual, and social cognitive tasks; semi-structured interviews, and the Structured Clinical Interview for<i>DSM-IV</i>Axis I disorders were administered every 6 months. The UHR status of nonconverters, converters, remitters, and nonremitters was monitored. Cognitive domain scores and functioning were investigated longitudinally. <h3>Results</h3> In total, 384 healthy controls and 173 UHR individuals between ages 14 and 29 years were evaluated prospectively. Of the 384 healthy controls, 153 (39.8%) were female and 231 (60.2%) were male with a mean (SD) age of 21.69 (3.26) years. Of the 173 individuals at UHR for psychosis, 56 (32.4%) were female and 117 (67.6%) were male with a mean (SD) age of 21.27 (3.52) years). After 24 months of follow-up, 383 healthy controls (99.7%) and 122 individuals at UHR for psychosis (70.5%) remained. Baseline cognitive deficits were associated with psychosis conversion later (mean odds ratio [OR], 1.66; combined 95% CI, 1.08-2.83;<i>P</i> = .04) and nonremission of UHR status (mean OR, 1.67; combined 95% CI, 1.09-2.95;<i>P</i> = .04). Five cognitive components—social cognition, attention, verbal fluency, general cognitive function, and perception—were obtained from principal components analysis. Longitudinal component structure change was observed in general cognitive function (maximum vertical deviation = 0.59; χ<sup>2</sup> = 8.03;<i>P</i> = .01). Group-by-time interaction on general cognitive function (<i>F</i> = 12.23; η<sup>2</sup> = 0.047;<i>P</i> &lt; .001) and perception (<i>F</i> = 8.33; η<sup>2</sup> = 0.032;<i>P</i> &lt; .001) was present. Changes in attention (<i>F</i> = 5.65; η<sup>2</sup> = 0.013;<i>P</i> = .02) and general cognitive function (<i>F</i> = 7.18; η<sup>2</sup> = 0.014;<i>P</i> = .01) accounted for longitudinal changes in social and occupational functioning. <h3>Conclusions and Relevance</h3> Individuals in this study who met the UHR criteria appeared to demonstrate cognitive deficits, and those whose UHR status remitted were seen to recover cognitively. Cognition appeared as poor in nonremitters and appeared to be associated with poor functional outcome. This study suggests that cognitive dimensions are sensitive to the identification of young individuals at risk for psychosis and to the longitudinal course of those at highest risk.