Group and site differences on the California Verbal Learning Test in persons with schizophrenia and their first-degree relatives: Findings from the Consortium on the Genetics of Schizophrenia (COGS)

Abstract

Genetic studies of schizophrenia focus increasingly on putative endophenotypes because their genetic etiology may be simpler than clinical diagnosis. The Consortium on the Genetics of Schizophrenia (COGS), a multisite family study, aims to identify the genetic basis of several endophenotypes including verbal declarative memory (VDM), a neurocognitive function that shows robust impairment in schizophrenia. We present data on one type of measure of VDM, the California Verbal Learning Test, Second Edition (CVLT-II), in schizophrenia probands (n=305), their full biological siblings (n=449) and parents (n=232), and in community comparison subjects (CCS; n=509) across seven sites. Probands performed more poorly on each of five CVLT-II measures compared to related sibling and parent groups and CCS. Siblings and parents performed significantly worse than CCS on one measure (Discriminability), but with smaller effect sizes and less impairment than observed previously. The results raise questions about the homogeneity of VDM as an endophenotype, about methodological issues related to sampling, and about psychometric issues that impact the utility of the CVLT for detecting VDM deficits in nonpsychotic relatives of persons with schizophrenia.

Paternal age of schizophrenia probands and endophenotypic differences from unaffected siblings

“…The CVLT is a list-learning test that assesses verbal learning and memory. The total recall score of a list of 16 verbally presented items summed across 5 trials is measured (Stone et al, 2011). …”

Recent Advances in the Genetics of Schizophrenia

“…The largest effort to investigate endophenotypes and identify linkage with schizophrenia has been the Consortium on the Genetics of Schizophrenia (COGS), a 7-site study funded by the National Institute of Mental Health. They have reported on the significant impairment of P50 inhibition [147], prepulse inhibition [149, 149], verbal declarative memory [150, 151], and working memory in schizophrenic patients and relatives compared to controls, and they identified smoking status as a moderator in the latter [152]. Positive but weaker results were also reported for the antisaccade task performance [153] and reduced auditory P300 amplitude [154].…”

Prioritizing schizophrenia endophenotypes for future genetic studies: An example using data from the COGS-1 family study

“…Results from COGS-1 have been reported by numerous authors (Greenwood et al, 2007; Greenwood et al, 2011; Greenwood et al, 2013; Horan et al, 2008; Light et al, 2014; Olincy et al, 2010; Radant et al, 2010; Radant et al, 2007; Radant et al, 2015; Stone et al, 2011; Swerdlow et al, 2007; Turetsky et al, 2007; Turetsky et al, 2008) and focus on describing the heritability and deficits in SZ probands of individual endophenotypes. The study described here uses statistical methods to investigate which combination of COGS-1 endophenotypes that we considered best distinguishes between SZ and healthy community comparison subjects (CCS) in a large, well-characterized sample.…”