Characterising cognitive heterogeneity in individuals at clinical high-risk for psychosis: a cluster analysis with clinical and functional outcome prediction

Kate Haining,Joachim Gross,Robin A A Ince,Peter J Uhlhaas,Andrew I Gumley,Stephen M Lawrie,Matthias Schwannauer,Ruchika Gajwani,Frauke Schultze-Lutter

doi:10.1007/s00406-021-01315-2

Abstract

Schizophrenia is characterised by cognitive impairments that are already present during early stages, including in the clinical high-risk for psychosis (CHR-P) state and first-episode psychosis (FEP). Moreover, data suggest the presence of distinct cognitive subtypes during early-stage psychosis, with evidence for spared vs. impaired cognitive profiles that may be differentially associated with symptomatic and functional outcomes. Using cluster analysis, we sought to determine whether cognitive subgroups were associated with clinical and functional outcomes in CHR-P individuals. Data were available for 146 CHR-P participants of whom 122 completed a 6- and/or 12-month follow-up; 15 FEP participants; 47 participants not fulfilling CHR-P criteria (CHR-Ns); and 53 healthy controls (HCs). We performed hierarchical cluster analysis on principal components derived from neurocognitive and social cognitive measures. Within the CHR-P group, clusters were compared on clinical and functional variables and examined for associations with global functioning, persistent attenuated psychotic symptoms and transition to psychosis. Two discrete cognitive subgroups emerged across all participants: 45.9% of CHR-P individuals were cognitively impaired compared to 93.3% of FEP, 29.8% of CHR-N and 30.2% of HC participants. Cognitively impaired CHR-P participants also had significantly poorer functioning at baseline and follow-up than their cognitively spared counterparts. Specifically, cluster membership predicted functional but not clinical outcome. Our findings support the existence of distinct cognitive subgroups in CHR-P individuals that are associated with functional outcomes, with implications for early intervention and the understanding of underlying developmental processes.

Highlights

Schizophrenia is a debilitating psychiatric disorder characterised by psychotic symptoms, including hallucinations and delusions, as well as impairments in cognition, sensory processing and psychosocial functioning [1, 2]
clinical high-risk for psychosis (CHR-P) individuals had significantly fewer years of education, greater symptom severity, higher likelihood of comorbid mood and anxiety disorders and poorer functioning compared to CHR-N and healthy controls (HCs) participants (Table 1)
We identified two discrete cognitive subgroups and found support for considerable cognitive heterogeneity within the CHR-P group

Summary

Introduction

Schizophrenia is a debilitating psychiatric disorder characterised by psychotic symptoms, including hallucinations and delusions, as well as impairments in cognition, sensory processing and psychosocial functioning [1, 2]. CHR-P individuals are characterised by widespread cognitive impairments intermediate between healthy controls (HC) and first-episode psychosis (FEP) patients [9, 10]. These impairments, especially in attention, working memory and declarative memory, are more pronounced in CHR-P individuals who later transition to psychosis [11]. Novel approaches may be required to identify subtypes of CHR-P participants with different cognitive profiles, with possible implications for the understanding of underlying pathophysiology and accurate prediction of outcomes

Results

Discussion

Conclusion