Global deficits in declarative memory are commonly reported in individuals with schizophrenia and psychotic bipolar disorder, and in their biological relatives. However, it remains unclear whether there are specific components within the global declarative memory dysfunction that are unique to schizophrenia and bipolar disorder, or whether these impairments overlap the two psychoses. This study sought to characterize differential components of learning and memory in individuals within the psychosis dimension: probands with schizophrenia (SZP, n = 33), probands with psychotic bipolar I disorder (BDP, n = 20), and biological relatives of SZP (SZR, n = 21), contrasted with healthy controls (HC, n = 26). A computerized cognitive paradigm, the Acquired Equivalence test, with probes for associative learning, memory for learned associations, and memory generalization was administered, along with standardized neuropsychological measures of declarative memory. All study groups were able to learn and remember the associations, although SZP were slower than HC in the initial learning stages. Both SZP (significantly) and BDP (at a trend level) showed altered memory generalization compared to HC (SZP vs. HC, p = .038, d = .8; BDP vs. HC, p = .069, d = .95). SZR showed memory generalization intermediate between SZP and HC, although their performance did not differ significantly from either group. These findings indicate that probands with schizophrenia and bipolar psychoses have similar alteration in the ability to flexibly generalize learned knowledge when probed with novel stimuli, despite overall sufficient associative learning and memory for what they learned. These results suggest that the two disorders present a clinical continuum with overlapping hippocampus-mediated memory generalization dysfunction underlying the psychosis phenotype.
Deficits in declarative memory (DM) are one of the broadly studied cognitive phenotypes of schizophrenia (SZ) and bipolar disorder (BD) commonly observed in both probands (Glahn et al., 2004, Schretlen et al., 2007, Arts et al., 2008, Hill et al., 2008 and Stefanopoulou et al., 2009) and their biological relatives (Toomey et al., 1998, Sitskoorn et al., 2004 and Glahn et al., 2010). Novel cognitive paradigms translated from animal and computational models have allowed the dissection of memory function (Myers et al., 2003, Titone et al., 2004, Preston et al., 2005 and Shohamy and Wagner, 2008) and provided evidence that a ‘global’ DM phenotype presents a complex array of cognitive processes including memory encoding and consolidation, retrieval and subsequent generalization of past memories to novel environments (Heckers et al., 1998, Myers et al., 2003, Titone et al., 2004, Preston et al., 2005 and Shohamy and Wagner, 2008). Deficits in generalizing learned information to novel choices, thought to be mediated by hippocampus (Heckers et al., 1998, Myers et al., 2003, Heckers et al., 2004, Shohamy and Wagner, 2008, Shohamy et al., 2010 and Eichenbaum et al., 2011), have been reported in SZ probands (SZP). Notably, these deficits are found despite intact associative learning and memory retention (Heckers et al., 2004, Keri et al., 2005, Ongur et al., 2006 and Shohamy et al., 2010). Furthermore, we have recently contrasted memory-based generalization performance in SZP on- and off-antipsychotic medication, and demonstrated a positive, yet not normalizing, effect of antipsychotics on memory generalization (Shohamy et al., 2010).
Growing evidence from translational and genetic studies suggests that psychosis, a clinical dimension overlapping empirically defined diagnostic categories (e.g., SZ and BD), may be associated with unique neurophysiological and molecular markers independent of the categorical diagnoses (see Ivleva et al., 2010 for review). Although ‘SZ-like’ DM alterations measured by neuropsychological tests have been reported in probands with psychotic BD (BDP) (Hill et al., 2008 and Glahn et al., 2010), specific phenotypes within DM have not been tested. Similarly, no previous studies have examined familial association of memory generalization. Therefore, building on prior work in SZ (Heckers et al., 1998, Titone et al., 2004 and Shohamy et al., 2010), here we extend the testing of memory-based generalization to BDP, as well as to biological relatives of SZP (SZR). We applied a version of the Acquired Equivalence (AE) paradigm (Myers et al., 2003) that allows a selective assessment of memory-based generalization. We hypothesized that 1) SZP and BDP would both show intact feedback-driven associative learning and subsequent memory for learned associations, but would be impaired at generalization of what they learned, with both groups performing similarly to each other and worse than healthy controls (HC); and, 2) SZR would show learning, memory for learned associations and generalization performance intermediate between SZP and HC. The study groups were matched on age and had equivalent levels of education and IQ, providing a similar baseline of cognition-relevant features for the DM phenotype characterization.
