The Palau Early Psychosis Study: Neurocognitive functioning in high-risk adolescents

Abstract Objective The purpose of the present study was to evaluate both the independent and joint effects of genetic risk and clinical status on neurocognitive functioning in adolescents from a population isolate with an elevated risk for schizophrenia and strong familial aggregation of cases. Method The subjects were 310 non-help seeking, drug-naïve adolescents 14–19 years of age from the Republic of Palau. The sample comprised 98 Genetically High Risk (GHR) adolescents, 54 of whom were symptomatic, and 212 Genetically Low Risk (GLR) adolescents, including 113 Clinically High Risk (CHR) subjects who were symptomatic and 99 normal controls who were non-symptomatic. Neurocognitive testing was conducted after the clinical assessment and included Wechsler Memory Scale tests of logical, visual and working memory, the perceptual organization and processing speed subtests of the WISC-III, CPT-IP measures of sustained attention, and tests of fine and gross neuromotor function. Results GHR adolescents showed impairments in immediate logical memory, verbal working memory, CPT-IP performance, and fine motor skills. The only two cognitive components influenced by the presence of early psychosis symptoms were WISC-III perceptual organization and spatial working memory. Neurocognitive deficits did not increase with increasing levels of psychopathology. We found no significant interactive effects of genetic risk and clinical status on neurocognitive functioning. Conclusions Genetic risk and clinical status exert independent effects on neurocognitive function in HR adolescents, and genetic risk has a broader impact than clinical status. Our results suggest that many of the neurocognitive impairments associated with early psychosis are genetically mediated and can occur in genetically vulnerable individuals regardless of their clinical status. However, visuospatial processing appears to be uniquely disrupted by emerging symptomatology.