TY - JOUR

T1 - Generalized neurocognitive impairment in individuals at ultra-high risk for psychosis

T2 - The possible key role of slowed processing speed

AU - Randers, Lasse

AU - Jepsen, Jens Richardt Møllegaard

AU - Fagerlund, Birgitte

AU - Nordholm, Dorte

AU - Krakauer, Kristine

AU - Hjorthøj, Carsten

AU - Glenthøj, Birte

AU - Nordentoft, Merete

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - at-risk mental state

KW - clinical high risk

KW - cognition

KW - neuropsychology

KW - schizophrenia

U2 - 10.1002/brb3.1962

DO - 10.1002/brb3.1962

M3 - Journal article

C2 - 33486897

AN - SCOPUS:85099963674

VL - 11

JO - Brain and Behavior

JF - Brain and Behavior

SN - 2157-9032

IS - 3

M1 - e01962

ER -