Cognitive endophenotypes of psychosis within dimension and diagnosis

Abstract

This study sought to characterize the psychosis phenotype, contrasting cognitive features within traditional diagnosis and psychosis dimension in a family sample containing both schizophrenia and psychotic bipolar I disorder. Seventy-six probands with psychosis [44 probands with schizophrenia, 32 probands with psychotic bipolar I disorder] and 55 first-degree relatives [30 relatives of schizophrenia probands, 25 relatives of bipolar probands] were recruited. Standardized clinical and neuropsychological measures were administered. No differences in cognitive performance emerged between probands with schizophrenia and probands with psychotic bipolar disorder, or between relatives of probands with schizophrenia and relatives of probands with bipolar disorder in the domains of working and declarative memory, executive function and attention. Relatives overall showed higher cognitive performance compared to probands, as expected. However, when we segmented the probands and relatives along a psychosis dimension, independent of diagnostic groups, results revealed lower cognitive performance in probands compared to relatives without psychosis spectrum disorders, whereas relatives with psychosis spectrum disorders showed an intermediate level of performance across all cognitive domains. In this study, cognitive performance did not distinguish either probands or their first-degree relatives within traditional diagnostic groups (schizophrenia and psychotic bipolar disorder), but distinguished probands and relatives with and without lifetime psychosis manifestations independent of diagnostic categories. These data support the notion that schizophrenia and psychotic bipolar disorder present a clinical continuum with overlapping cognitive features defining the psychosis phenotype.

Figure 1. Cognitive Profiles of Probands with Schizophrenia and Psychotic Bipolar I Disorder, and their First - Degree Relatives by Traditional Diagnoses (A) and Psychosis Dimension (B)

Between group differences based on a mixed - effect repeated measure analysis (PROC MED): * p < .05, ** p < .01, *** p < .001 SZP – probands with schizophrenia, BDP – probands with psychotic bipolar I disorder, SZR – relatives of SZP, BDR – relatives of BDP, Rel-Psychotic – relatives with psychosis spectrum disorders, Rel-Nonpsychotic – relatives without psychosis spectrum disorders; DIGSYM – Digit Symbol Coding, LNS – Letter Number Sequencing, SS – Spatial Span, LM II – Logical Memory II, WAR-W – Warrington Word Recognition, WAR-F – Warrington Face Recognition, WCST – Wisconsin Card Sort Test – Perseverative Response, TMT-B – Trial Making Test B Time, LF – Letter Fluency, TMT-A – Trial Making Test A Time; WM – Working Memory Composite, DM – Declarative Memory Composite, EF – Executive Function Composite, AT – Attention, GNC – Global Neuropsychological Composite