Unitary construct of generalized cognitive ability underlying BACS performance across psychotic disorders and in their first-degree relatives
Introduction
Cognitive deficits have been firmly established as a common debilitating feature of schizophrenia spectrum disorders (Bilder et al., 2000, Dickinson et al., 2008, Hill et al., 2004, Keefe et al., 2006, Reilly and Sweeney, 2014). These deficits are present at illness onset, stable, and minimally affected by antipsychotic treatment (Bilder et al., 2000, Hill et al., 2004, Hoff et al., 1999), and predict functional outcome (Bowie and Harvey, 2006, Green, 1996). A less severe pattern of generalized deficits has been reported in affective psychotic disorders and in first-degree relatives of patients with both affective and nonaffective psychotic disorders (Hill et al., 2014). However, the factor structure of deficits across disorders and in family members has not been systematically examined in a single study.
The Brief Assessment of Cognition in Schizophrenia (BACS) neuropsychological battery was designed to be easily and quickly administered (in < 35 min), and sensitive to the profile of generalized impairment seen in schizophrenia (Keefe et al., 2004, Keefe et al., 2008). This scale has been widely used in schizophrenia research, especially in clinical trials as a cognitive outcome measure. Factor analytic research with schizophrenia patients has indicated that a single generalized factor accounts for a high percentage of the variance in scores on both the BACS (Hill et al., 2008) and larger neuropsychological batteries (Dickinson et al., 2006, Keefe et al., 2006), though additional factors have been identified in some studies. However, few studies have examined the degree to which the cognitive architecture of performance across a battery of neuropsychological measures is consistent across psychotic disorders, whether these latent constructs in patients are similar to those of their first-degree relatives (Sitskoorn et al., 2004, Snitz et al., 2006), and whether those structures are similar to that seen in healthy controls. These issues are important for diagnostic differentiation and to support the use of neuropsychological batteries as outcome measures across disorders.
The BACS was used by the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium to address questions about diagnostic boundaries and familiarity of intermediate phenotypes in schizophrenia, schizoaffective disorder, and bipolar disorder. The initial report of cognitive deficits showed significant familiality and differences across disorders in the severity of deficit (Hill et al., 2014), but the composition of the deficit across disorders and in family members was not formally addressed previously and is the focus of this investigation. To date, no other studies have examined such a range of diagnostic and family groups in a large study of this nature. Clarifying the latent variable structure across disorders and any differences across groups is important to establish the utility of the BACS and other measures of general intellectual ability in assessing cognition across a broad range of psychiatric populations in clinical trials, and in tracking cognitive phenotypes in family genetic research.
A two-step, split-half, cross-validation method using complimentary exploratory and confirmatory factor analytic techniques (Gorsuch, 1983) was first applied to each subject group separately. Then, exploratory factor analysis (EFA) was conducted on half of each group (randomly selected) to determine the number of latent factors underlying BACS subscales in a data driven manner. The remaining half of each group was then separately examined using a confirmatory factor analysis (CFA) to validate the findings. The primary scientific questions pertained to the homogeneity of factor structure across proband groups, between proband groups and their respective family members, and between these groups and healthy controls.
Section snippets
Participants
Recruitment strategy and patient characteristics of the BSNIP study sample have been reported previously (Tamminga et al., 2014). Patients were recruited from the community if they had a history of psychotic symptoms and at least one first-degree relative between the ages of 15–65 also willing to participate in the study. Probands were required to have a DSM-IV diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder with a history of psychotic symptoms determined using the
Exploratory factor analyses
As illustrated in Fig. 1, findings clearly indicated a one-factor solution in all groups (see Table 2 for the amount of variance explained for each group). Because a single factor was extracted in all groups, there was no rotation or evaluation of factor correlations. Overall, these findings indicate a single, generalized cognitive factor underlying the BACS in all diagnostic groups, their relatives, and in healthy controls. As can be seen in Table 2, all subtests loaded meaningfully, and
Discussion
This study was the first to examine the cognitive architecture underlying the BACS battery and the structure of generalized cognitive impairment across psychotic disorders (schizophrenia, schizoaffective, and psychotic bipolar) and their first-degree relatives. A split-half, cross-validation analysis starting with a data-driven exploratory factor analytic technique was conducted separately for each group. Results indicated a single-factor solution underlying BACS performance that was similar in
Role of funding source
The funding agencies had no role in the design and conduct of the study collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
Contributors
Mr. Hochberger is the lead author and was involved in all aspects of the report. Dr. Hill was involved in all aspects of the report. Dr. Sweeney is the senior author, was a site PI, and was involved in all aspects of the report. Ms. Nelson was involved in data analysis, literature review, compilation of the main tables, and writing early drafts of the report. Dr. Reilly has been involved in all aspects of the project including data collection, clinical characterization, data processing and
Conflict of interest
Dr. Tamminga has received support from Intracellular Therapies (ITI, Inc.), PureTech Ventrues, Eli Lilly Pharmaceuticles, Sunovion, Astellas, Merck (ad hoc consulting), International Congress on Schizophrenia Research (unpaid volunteer), NAMI (unpaid volunteer), American Psychiatric Association (Deputy Editor), and Finnegan Henderson Farabow Garrett & Dunner, LLP. Dr. Keefe has received investigator-initiated support from the Department of Veteran's Affair, Feinstein Institute for Medical
Acknowledgments
This study was supported in part by NIMH grants MH078113, MH077945, MH077852, MH077851, MH077862, MH072767, and MH083888.
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