Factor structure of cognition and functional capacity in two studies of schizophrenia and bipolar disorder: Implications for genomic studies.

Abstract

Objective Impairments in cognition and everyday functioning are common in schizophrenia and bipolar disorder. Based on two studies of schizophrenia (SCZ) and bipolar I disorder (BPI) with similar methods, this paper presents factor analyses of cognitive and functional capacity (FC) measures. The overall goal of these analyses was to determine whether performance-based assessments should be examined individually, or aggregated on the basis of the correlational structure of the tests and as well as to evaluate the similarity of factor structures in SCZ and BPI. Method Veterans Affairs (VA) Cooperative Studies Program study #572, evaluated cognitive and FC measures among 5,414 BPI and 3,942 SZ patients. A second study evaluated similar neuropsychological (NP) and FC measures among 368 BPI and 436 SZ patients. Principal components analysis, as well as exploratory and confirmatory factor analyses, were used to examine the data. Results Analyses in both datasets suggested that NP and FC measures were explained by of a single underlying factor in BPI and SCZ patients, both when analyzed separately or as in a combined sample. The factor structure in both studies was similar, with or without inclusion of FC measures; homogeneous loadings were observed for that single factor across cognitive and FC domains across the samples. Conclusions The empirically derived factor model suggests that NP performance and FC are best explained as a single latent trait applicable to people with schizophrenia and bipolar illness. This single measure may enhance the robustness of the analyses relating genomic data to performance-based phenotypes.

Characterizing cognitive heterogeneity on the schizophrenia–bipolar disorder spectrum

“…That the cross-diagnostic cluster-solution was replicated using only a general cognitive factor as a clustering variable, suggests that a 'g' factor can be examined with some confidence in empirical clustering studies in even larger, 'messier' datasets that comprise different cognitive batteries. This has obvious implications for the genomic analyses of large-scale datasets focused on intra-individual differences in cognition in BD and SZ (Harvey et al, 2016, Harvey et al, 2014, and studies measuring the overlap between cognition and risk for psychiatric disease more broadly (Lencz et al, 2014, Hatzimanolis et al, 2015, Hill et al, 2016, Gale et al, 2008.…”

Brain structure, cognition, and brain age in schizophrenia, bipolar disorder, and healthy controls

“…This was followed by post hoc pairwise voxel-wise comparisons across groups. Analysis 2: association between cognitive performance and brain structure Given the large body of evidence of one or two factors explaining the majority of the variance in cognitive function in healthy subjects [40][41][42][43] as well as in individuals with schizophrenia and BD [21,22], we chose to perform principal component analysis (PCA) as a data reduction step to reduce multiple comparisons. We then used a general linear model to assess whether the principal component factor scores were associated with cortical thickness and/or FA, controlling for sex, age, and parental education in all participants collapsed together, as well as separately within each diagnosis.…”

“…Therefore, the relationships among brain structure, cognitive performance, serious mental illness, and aging require further disentanglement. Cognitive variability has been shown to be captured by a single factor in both schizophrenia and BD [21,22]. There also remains some debate regarding altered neurodevelopmental versus (early) neurodegenerative trajectories of the major psychoses (i.e., "an early hit" versus an accelerated aging mechanism), especially in schizophrenia.…”

Neuregulin 3 rs10748842 polymorphism contributes to the effect of body mass index on cognitive impairment in patients with schizophrenia

“…Genetic variance is one such mechanism and it is well established that certain genes predispose patients to cognitive impairment 7 . The heritability range varies in different domains in patients with schizophrenia, including working memory (0.3-0.6), executive function (0.3-0.6), episodic memory (0.3-0.6), and attention (0.54) 8 . Additional evidence has indicated that cognitive impairment often occurs in unaffected relatives of patients with schizophrenia 9,10 .…”