Verbal recall and recognition in twins discordant for schizophrenia
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.
References (69)
- et al.
The inheritance of neuropsychological dysfunction in twins discordant for schizophrenia
American Journal of Human Genetics
(2000) - et al.
The measurement of differential deficit
Journal of Psychiatric Research
(1978) - et al.
Neuropsychologic functioning among the nonpsychotic relatives of schizophrenic patients: the effect of genetic loading
Biological Psychiatry
(2000) - et al.
Hippocampal gray matter reduction associates with memory deficits in adolescents with history of prematurity
NeuroImage
(2004) - et al.
Genetic risk of neuropsychological impairment in schizophrenia: a study of monozygotic twins discordant and concordant for the disorder
Schizophrenia Research
(1995) - et al.
A meta-analytic review of the effects of acute cortisol administration on human memory
Psychoneuroendocrinology
(2005) - et al.
Schizophrenia and cognitive function
Current Opinion in Neurobiology
(2000) - et al.
Verbal learning and memory in relatives of schizophrenics: preliminary findings
Biological Psychiatry
(1995) - et al.
Amygdala-hippocampal volume and verbal memory in first-degree relatives of schizophrenic patients
Psychiatry Research
(2001) - et al.
Cognitive and clinical moderators of recognition memory in schizophrenia: a meta-analysis
Schizophrenia Research
(2005)
Cognitive deficits in relatives of patients with schizophrenia: a meta-analysis
Schizophrenia Research
Verbal memory processes in schizophrenia patients and biological relatives of schizophrenia patients: intact implicit memory, impaired explicit recollection
Schizophrenia Research
Memory tests in first-degree adult relatives of schizophrenic patients: a meta-analysis
Schizophrenia Research
Impaired hippocampal recruitment during normal modulation of memory performance in schizophrenia
Biological Psychiatry
Declarative memory in unaffected adult relatives of patients with schizophrenia: a systematic review and meta-analysis
Schizophrenia Research
Episodic memory-related activation in schizophrenia: meta-analysis
British Journal of Psychiatry
Memory impairment in schizophrenia: a meta-analysis
American Journal of Psychiatry
DSM IV: Diagnostic and Statistical Manual of Mental Disorders
The Scale for the Assessment of Negative Symptoms (SANS)
The Scale for the Assessment of Positive Symptoms (SAPS)
Volumes of brain structures in twins discordant for schizophrenia
Archives of General Psychiatry
Recall and recognition in chronic nondemented schizophrenics: use of matched tasks
Journal of Abnormal Psychology
Recall and Recognition in mildly disturbed schizophrenics: the use of matched tasks
Psychological Medicine
Regional gray matter, white matter, and cerebrospinal fluid distributions in schizophrenic patients, their siblings, and controls
Archives of General Psychiatry
Cortex mapping reveals regionally specific patterns of genetic and disease-specific gray-matter deficits in twins discordant for schizophrenia
Proceedings of the National Academy of Sciences of the United States of America
Problems in the measurement of cognitive deficit
Psychological Bulletin
Verbal declarative memory dysfunction in schizophrenia: from clinical assessment to genetics and brain mechanisms
Neuropsychology Review
A coefficient of agreement for nominal scales
Educational and Psychological Measurement
Hippocampal system and declarative (relational) memory: summarizing the data from functional neuroimaging studies
Hippocampus
The stress cascade and schizophrenia: etiology and onset
Schizophrenia Bulletin
Neuropsychological change in young people at high risk for schizophrenia: results from the first two neuropsychological assessments of the Edinburgh High Risk Study
Psychological Medicine
Frontal lobe contributions to recognition and recall: linking basic research with clinical evaluation and remediation
Journal of the International Neuropsychological Society
The California Verbal Learning Test
Remembering episodes: a selective role for the hippocampus during retrieval
Nature Neuroscience
Cited by (20)
TCF4 gene polymorphism is associated with cognition in patients with schizophrenia and healthy controls
2015, Journal of Psychiatric ResearchCitation Excerpt :They persist throughout the course of illness (Rund, 1998; Hughes et al., 2003) and have been found across almost all cognitive domains, including attention, learning, language, memory, executive function, and processing speed (Harvey et al., 2004; Mclntosh et al., 2011; Hui et al., 2013). Moreover, the deficit of verbal memory in schizophrenia is found to be the most pronounced in several European studies (Heinrichs and Zakzanis, 2014; Cannon et al., 2000; Faraone et al., 2000; Van Erp et al., 2008). Cognitive impairment could have a debilitating effect on the standard of living in schizophrenia as it may influence treatment, rehabilitation, quality of life, and even employment of the patients (Granholm et al., 2008; Kaneda et al., 2009; Harvey, 2009).
Cytomegalovirus seropositivity and serointensity are associated with hippocampal volume and verbal memory in schizophrenia and bipolar disorder
2014, Progress in Neuro-Psychopharmacology and Biological PsychiatryCitation Excerpt :Considering the association of CMV with cognitive deficits in schizophrenia and BD, its gray matter, limbic and temporal affinity, and the known hippocampal dysfunctions in BD and schizophrenia, we hypothesized that CMV seropositivity and/or antibody levels would be associated with altered hippocampal volume and function, as measured by a verbal memory test in patients. The CVLT (California Verbal Learning Test) is a widely used test of episodic verbal memory in psychiatric populations and is strongly but not exclusively, related to hippocampal functioning (Alexander et al., 2003; Chepenik et al., 2012; van Erp et al., 2008). We included two groups of patients, schizophrenia and BD, as elevated rates of CMV antibodies do not seem specific to schizophrenia but are also present in patients with BD (Tedla et al., 2011; Torrey et al., 1982).
Hippocampal shape abnormalities of patients with childhood-onset schizophrenia and their unaffected siblings
2013, Journal of the American Academy of Child and Adolescent PsychiatryNeurocognitive profile and its association with psychopathology in first-degree relatives of patients with schizophrenia. A case-control study
2012, Psychiatry ResearchCitation Excerpt :However, it should be noted that literature on WCST performance in SCZ-RELs is still conflicting (Goldberg et al., 1990; Scarone et al., 1993; Stratta et al., 1997; Thompson et al., 2005; Breton et al., 2011) and caution should be adopted when interpreting our results. Moreover, since deficits on memory tasks (possibly involving hippocampal structures) have been also found in unaffected relatives of patients with schizophrenia (Sitskoorn et al., 2004; Conklin et al., 2005; van Erp et al., 2008), the involvement of other brain regions may be reasonably hypothesized. Regarding the second study hypothesis, we found that SCZ-RELs showed higher levels of negative symptoms as compared to NCs.
Differences in subcortical structures in young adolescents at familial risk for schizophrenia: A preliminary study
2012, Psychiatry Research - NeuroimagingCitation Excerpt :These findings are consistent with previous reports suggesting that the disorganization domain may index many of the cognitive deficits of the schizophrenia spectrum (Demjaha et al., 2012). Such deficits are among the earliest symptomatic manifestations of disease and/or disease risk (Jones et al., 1994) and also associated with diminished subcortical volumes in high-risk samples (Bhojraj et al., 2011; Hannan et al., 2010; van Erp et al., 2008). Our results did not survive FDR adjustment and thus should be interpreted cautiously, especially in light of the potential non-specificity of disorganization symptoms.
Postnatal choline levels mediate cognitive deficits in a rat model of schizophrenia
2012, Pharmacology Biochemistry and Behavior