Elsevier

Psychiatry Research

Volume 159, Issue 3, 30 June 2008, Pages 271-280
Psychiatry Research

Verbal recall and recognition in twins discordant for schizophrenia

https://doi.org/10.1016/j.psychres.2007.03.003Get rights and content

Abstract

The nature, neural underpinnings, and etiology of deficits in verbal declarative memory in patients with schizophrenia remain unclear. To examine the contributions of genes and environment to verbal recall and recognition performance in this disorder, the California Verbal Learning Test was administered to a large population-based Finnish twin sample, which included schizophrenic and schizoaffective patients, their non-ill monozygotic (MZ) and dizygotic (DZ) co-twins, and healthy control twins. Compared with controls, patients and their co-twins showed relatively greater performance deficits on free recall compared with recognition. Intra-pair differences between patients and their non-ill co-twins in hippocampal volume and memory performance were highly positively correlated. These findings are consistent with the view that genetic influences are associated with reduced verbal recall in schizophrenia, but that non-genetic influences further compromise these abnormalities in patients who manifest the full-blown schizophrenia phenotype, with this additional degree of disease-related declarative memory deficit mediated in part by hippocampal pathology.

Introduction

Deficits in verbal learning and memory are robust correlates of schizophrenia (Heinrichs and Zakzanis, 1998, Aleman et al., 1999, Kuperberg and Heckers, 2000, Cirillo and Seidman, 2003, Pelletier et al., 2005). Hypotheses about the cognitive underpinnings of these deficits include an inability to use efficient strategies spontaneously during encoding and/or retrieval, reduced conscious recollection and increased reliance on familiarity assessment as a basis for retrieval, and reduced monitoring processes during retrieval, processes thought to be mediated by prefrontal and medial temporal lobe regions (Achim and Lepage, 2005). A meta-analysis found that the degree of difference in performance on memory tests between schizophrenic patients and controls, expressed in terms of effect size, declines with an increase in the amount of contextual information provided at test (free recall < cued recall < recognition) (Aleman et al., 1999). Arguing against the interpretation that this differential level of deficit is an artifact of the discriminating power of the performance measure employed (Chapman and Chapman, 1973, Chapman and Chapman, 1978) is a report that chronic non-demented schizophrenic patients showed a larger deficit on a free recall compared with a performance-matched recognition task (Calev, 1984a). This result was obtained despite the higher reliability for the recognition task, which would have predicted a higher discriminating power for the recognition versus the recall task, (but also see Calev, 1984b, Mohamed et al., 1999).

Several reviews have concluded that mean verbal recall performance is among the measures that show strong familial effects in relatives of schizophrenic patients (Sitskoorn et al., 2004, Whyte et al., 2005, Trandafir et al., 2006). A study that included non-ill relatives with either one or multiple first-degree relatives diagnosed with schizophrenia showed that deficits in story recall scaled with the level of genetic predisposition for the disorder (Faraone et al., 2000). Three twin reports including MZ twin pairs discordant for schizophrenia as well as control twins found that patients performed significantly worse than their co-twins, who performed significantly worse than the healthy twins on a story recall task, suggesting disease-related as well as familial influences on verbal memory performance in schizophrenia (Goldberg et al., 1990, Goldberg et al., 1993, Goldberg et al., 1995). Furthermore, one report showed that patients from concordant pairs did not differ from patients from discordant pairs, suggesting a similar etiology of the observed performance deficits in both groups (Goldberg et al., 1995). A previous report on this sample, which includes both MZ and DZ twin pairs discordant for schizophrenia as well as groups of healthy MZ and DZ twin pairs, examined free recall (story and verbal list items) as part of a canonical discriminant analysis, and showed that tests of verbal declarative memory contributed to the discrimination of patients from their own MZ co-twins (Cannon et al., 2000).

The majority of the studies including relatives of schizophrenic patients have examined performance on free recall of stories or word lists. Two recent meta-analytic studies concluded that too few studies have compared free recall, cued recall, and recognition for the same test in patients with schizophrenia and their relatives (Whyte et al., 2005, Trandafir et al., 2006) such that no firm conclusions can be drawn about the existence or not of retrieval deficits (Trandafir et al., 2006). Some studies have observed deficits in recognition hits among relatives of schizophrenic patients (Lyons et al., 1995), while others have not (Keri et al., 2001, Sponheim et al., 2004). One study showed that relatives performed worse on cued recall compared with controls (Sponheim et al., 2004).

To our knowledge, no study with schizophrenic patients' relatives at multiple levels of genetic predisposition has compared performance on free recall, cued recall, and recognition. The comparison of free recall, cued recall, and recognition provides a manipulation of the extent to which self-initiated strategic retrieval is needed to perform the task (Davidson et al., 2006). Encoding and consolidation are required in any of these conditions, but the conditions differ in the extent to which they require active retrieval (free recall > cued recall > recognition).

Evidence from neuroimaging studies of declarative memory in schizophrenia are consistent with reduced organizational processing at encoding as well as at retrieval and reduced post-retrieval monitoring, which may mainly involve the frontal lobes, and with less efficient associative encoding processes and a deficit in conscious recollection involving the hippocampus and medial temporal lobes (Achim and Lepage, 2005), regions that are known to be disrupted in patients with schizophrenia and their relatives.

The primary aim of the current paper was to determine the genetic and environmental influences on free recall, cued recall, and recognition performance in twins discordant for schizophrenia. Based on the foregoing, we predicted that patients and their co-twins would show relatively greater memory deficits compared with controls on conditions requiring active retrieval (free recall > cued recall > recognition), with the degree of deficit in co-twins varying in proportion to their genetic proximity to an affected individual. We also predicted that patients would show a greater deficit in recall and recognition compared with their own co-twins, possibly due to deficits in encoding and/or conscious recollection, and that these differences would be related to intra-pair differences in hippocampal volume.

Section snippets

Methods

The study protocol was reviewed and approved by the institutional review boards (IRBs) of the University of California (Los Angeles) and the National Public Health Institute of Finland, and all participants signed IRB-approved informed consent forms.

Number correct

There were significant effects of risk group [F(3,247) = 42.13, P < 0.0001], trial type [F(2,497) = 20.11, P = < 0.0001], risk group × trial type interaction [F(6,497) = 7.12, P < 0.0001], sex [F(1,103) = 15.03, P = 0.0001], and a marginally significant effect of age [F(1,104) = 3.19, P = 0.08] in predicting the number of words retrieved on the CVLT (Fig. 1). The slope across risk groups (Proband < MZ-cotwin < DZ-cotwin < Healthy) was steeper for free recall [t497 = 33.41, P = < 0.0001] and cued recall [t497 = 17.37, P = < 0.0001]

Discussion

The principal finding of the study is that the effect of genetic predisposition to schizophrenia on verbal declarative memory performance is larger on the free recall compared with the recognition condition of the CVLT (Fig. 1 and Table 3). Furthermore, intra-pair differences in left hippocampal volumes between patients and their co-twins correlate significantly with intra-pair differences in verbal declarative memory performance. Consistent with previous reports we found female superiority in

Acknowledgements

This research was supported by National Institute of Mental Health grant MH52857 (to T.D.C.). The authors thank Ulla Mustonen, Pirjo Käki, and Eila Voipio for their contributions to subject recruitment and evaluation, Antti Tanskanen for his contributions to the register searches, Kauko Heikkilä for his contributions to data management of the Finnish Twin Cohort Study, and the Finnish twins for participation in the study.

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