Neuropsychological Performance Among Individuals at Clinical High-Risk for Psychosis vs Putatively Low-Risk Peers With Other Psychopathology: A Systematic Review and Meta-Analysis

Abstract

Background and hypothesis: Youth at clinical high-risk (CHR) for psychosis present with neuropsychological impairments relative to healthy controls (HC), but whether these impairments are distinguishable from those seen among putatively lower risk peers with other psychopathology remains unknown. We hypothesized that any excess impairment among CHR cohorts beyond that seen in other clinical groups is minimal and accounted for by the proportion who transition to psychosis (CHR-T).

Study design: We performed a systematic review and meta-analysis of studies comparing cognitive performance among CHR youth to clinical comparators (CC) who either sought mental health services but did not meet CHR criteria or presented with verified nonpsychotic psychopathology.

Study results: Twenty-one studies were included representing nearly 4000 participants. Individuals at CHR showed substantial cognitive impairments relative to HC (eg, global cognition: g = -0.48 [-0.60, -0.34]), but minimal impairments relative to CC (eg, global cognition: g = -0.13 [-0.20, -0.06]). Any excess impairment among CHR was almost entirely attributable to CHR-T; impairment among youth at CHR without transition (CHR-NT) was typically indistinguishable from CC (eg, global cognition, CHR-T: g = -0.42 [-0.64, -0.19], CHR-NT: g = -0.09 [-0.18, 0.00]; processing speed, CHR-T: g = -0.59 [-0.82, -0.37], CHR-NT: g = -0.12 [-0.25, 0.07]; working memory, CHR-T: g = -0.42 [-0.62, -0.22], CHR-NT: g = -0.03 [-0.14, 0.08]).

Conclusions: Neurocognitive impairment in CHR cohorts should be interpreted cautiously when psychosis or even CHR status is the specific clinical syndrome of interest as these impairments most likely represent a transdiagnostic vs psychosis-specific vulnerability.

Keywords: clinical staging; developmental psychopathology; neurocognitive; schizophrenia; transdiagnostic.

Fig. 1.

PRISMA flow diagram depicting study selection procedure.

Fig. 2.

Panel A: Neurocognitive performance among individuals at CHR for psychosis and CCs, with HCs as the reference. Panel B: Neurocognitive performance among individuals at CHR for psychosis with CCs as the reference. Bars represent Hedge’s g effect size with 95% confidence intervals; more negative values indicate poorer performance relative to the reference group. CHR, clinical high-risk, CC, clinical comparator, HC, healthy control, CI, confidence interval.

Fig. 3.

Baseline neurocognitive functioning among individuals at clinical high-risk for psychosis plotted by whether they later developed a psychotic disorder, with baseline cognitive functioning of clinical comparators as the reference. Bars represent Hedge’s g effect size with 95% confidence intervals; more negative values indicate poorer performance. CHR-T, clinical high-risk with later transition to psychosis, CHR-NT, clinical high-risk without later transition to psychosis, CC, clinical comparator, CI, confidence interval.