Generalized neurocognitive impairment in individuals at ultra-high risk for psychosis: The possible key role of slowed processing speed.

Objective Widespread neurocognitive impairment is well-established in individuals at ultra-high risk (UHR) for developing psychoses, but it is unknown whether slowed processing speed may underlie impairment in other neurocognitive domains, as found in schizophrenia. The study delineated domain functioning in a UHR sample and examined if neurocognitive slowing might account for deficits across domains. Methods The cross-sectional study included 50 UHR individuals with no (n = 38) or minimal antipsychotic exposure (n = 12; mean lifetime dose of haloperidol equivalent = 17.56 mg; SD = 13.04) and 50 matched healthy controls. Primary analyses compared group performance across neurocognitive domains before and after covarying for processing speed. To examine the specificity of processing speed effects, post hoc analyses examined the impact of the other neurocognitive domains and intelligence as covariates. Results UHR individuals exhibited significant impairment across all neurocognitive domains (all ps ≤ .010), with medium to large effect sizes (Cohen's ds = -0.53 to -1.12). Only processing speed used as covariate eliminated significant between-group differences in all other domains, reducing unadjusted Cohen's d values with 68% on average, whereas the other domains used as covariates averagely reduced unadjusted Cohen's d values with 20% to 48%. When covarying each of the other domains after their shared variance with speed of processing was removed, all significant between-group domain differences remained (all ps ≤ .024). Conclusion Slowed processing speed may underlie generalized neurocognitive impairment in UHR individuals and represent a potential intervention target.