Cognitive Subtyping in Schizophrenia: A Latent Profile Analysis

Abstract

Cognitive dysfunction is a core feature of schizophrenia. The subtyping of cognitive performance in schizophrenia may aid the refinement of disease heterogeneity. The literature on cognitive subtyping in schizophrenia, however, is limited by variable methodologies and neuropsychological tasks, lack of validation, and paucity of studies examining longitudinal stability of profiles. It is also unclear if cognitive profiles represent a single linear severity continuum or unique cognitive subtypes. Cognitive performance measured with the Brief Assessment of Cognition in Schizophrenia was analyzed in schizophrenia patients (n = 767). Healthy controls (n = 1012) were included as reference group. Latent profile analysis was performed in a schizophrenia discovery cohort (n = 659) and replicated in an independent cohort (n = 108). Longitudinal stability of cognitive profiles was evaluated with latent transition analysis in a 10-week follow-up cohort. Confirmatory factor analysis (CFA) was carried out to investigate if cognitive profiles represent a unidimensional structure. A 4-profile solution was obtained from the discovery cohort and replicated in an independent cohort. It comprised of a “less-impaired” cognitive subtype, 2 subtypes with “intermediate cognitive impairment” differentiated by executive function performance, and a “globally impaired” cognitive subtype. This solution showed relative stability across time. CFA revealed that cognitive profiles are better explained by distinct meaningful profiles than a severity linear continuum. Associations between profiles and negative symptoms were observed. The subtyping of schizophrenia patients based on cognitive performance and its associations with symptomatology may aid phenotype refinement, mapping of specific biological mechanisms, and tailored clinical treatments.

A neuropsychological study on Leonhard’s nosological system

“…The results from a recent meta-analysis found support for three distinct cognitive subgroups reliably estimated (relatively intact, intermediate cognitive, a subgroup defined by mixed and a globally impaired subgroup) [62]. Four groups were created by means of structural equation models using an empirical data-driven approach [9].…”

“…Schizophrenia and other psychoses share a common profile of cognitive deficits that seem to be stable over the long term [6]. However, there is considerable within-and betweensubject heterogeneity across psychotic disorders [7][8][9].…”

Frontal neural metabolite changes in schizophrenia and their association with cognitive control: A systematic review

“… Hoonakker et al, 2017 ; Saykin et al, 1994 ) and executive functioning (e.g. Hutton and Kennard, 1998 ; Lim et al, 2021 ; Storchak et al, 2021 ). Successful goal-directed actions require adequate planning, and subsequent adjustment of behaviour determined by acquiring task-specific information and ignoring interfering stimuli.…”

Higher brain structural heterogeneity in schizophrenia

“…For example, although patients with schizophrenia are usually reported to have deficits in intellectual decline after illness onset, there is a fair proportion of patients do not (8). Distinct subtypes of schizophrenia usually demonstrate different or even totally opposite patterns of structural/functional abnormalities (7,(9)(10)(11). The heterogeneity is thought to be one of the leading causes that lead to conflicting findings in neuroimaging studies (12,13).…”