Impairment of visuospatial memory is associated with decreased slow wave sleep in schizophrenia
Introduction
Schizophrenia is a severely debilitating disorder. Whereas management of the positive symptoms has efficiently been established, treatment of cognitive impairment and neuropsychological deficits still is a challenge in the field. Moreover, it is the latter symptoms that play the major part in quality of life and psychological well-being (Green et al., 2000). Overcoming these debilitating neuropsychological handicaps would considerably improve well-being and psychosocial as well as occupational outcome in these patients. Our approach in this respect is to investigate a putative interrelationship between these neuropsychological deficiencies and variables of polysomnographic night sleep. We hypothesize that memory deficits are associated with impairment in particular variables of night sleep.
On the one hand, there are numerous studies on impairment in learning and memory in individuals with schizophrenia (e.g. Paulsen et al., 1995; Aleman et al., 1999; Mohamed et al., 1999). On the other hand, there is a body of literature on sleep disturbances, such as increased sleep onset latency and sleep fragmentation in patients with schizophrenia compared to healthy controls (e.g. Lauer et al., 1997; for review: Benca et al., 1992; Benson and Zarcone, 2000). In addition, several studies found a reduction in SWS or stage 4 sleep in schizophrenia (Hiatt et al., 1985; Keshevan et al., 1998; Poulin et al., 2003). In humans as well as in animals it has been shown that sleep plays a pivotal role in memory consolidation (for review: Peigneux et al., 2001; Stickgold et al., 2001). Consolidation of procedural memory, i.e. the “knowing how”, is associated with REM sleep (for review: Smith, 2001). Consolidation of declarative memory i.e. the “knowing that”, was shown to be associated with SWS (Plihal and Born, 1997, Plihal and Born, 1999). With respect to spatial memory, which, if explicit, is a subcategory of declarative memory, animal studies demonstrated that specific hippocampal cells activated during a spatial memory task are reactivated during subsequent sleep (Wilson and McNaughton, 1994). Staba and colleagues (2002) demonstrated in humans, that during SWS hippocampal neurons fired significantly more intensively than during REM sleep. The importance of the hippocampus for declarative or spatial memory is well established (e.g. Teng et al., 2000; for review see: Squire and Zola-Morgan, 1991; Burgess et al., 2002; Shu et al., 2003), and the thalamus plays a critical role for declarative or spatial memory as well (e.g. Zola-Morgan and Squire, 1985; Exner et al., 2001, Van Groen et al., 2002; Van der Werf et al., 2003; for review see: Shu et al., 2003). In schizophrenia, structural and functional abnormalities of the hippocampus have been unanimously demonstrated by a great number of various studies (e.g. Hulshoff Pol et al., 2001; Falkai et al., 2002; Ende et al., 2003; Ehrenreich et al., 2004; for review see Falkai et al., 2001). Abnormalities in the thalamus have also been shown (e.g. Ende et al., 2003; Danos et al., 2003). Moreover, recent studies reported on correlations between abnormalities in the above mentioned brain regions and neuropsychological test performance in individuals with schizophrenia (e.g. Weiss et al., 2003; Salgado-Pineda et al., 2003; for review see: Weiss and Heckers, 2001). Furthermore, the thalamus is known as a key pace maker in the regulation of SWS (Steriade et al., 1993).
Therefore, we hypothesize that impaired visuospatial, so to speak hippocampus-related, memory is associated with reduced amounts of SWS in individuals with schizophrenia. We investigated memory performance overnight in the morning after polysomnography in patients with schizophrenia and in healthy matched controls. We tested for procedural and visuospatial memory. To the best of our knowledge, except for a paper looking only for REM sleep parameters (Taylor et al., 1992), this is the first study applying polysomnography and memory testing in parallel and trying to link these parameters in patients with schizophrenia. So, this pilot study is meant to stimulate further research in this area and to maybe enable innovative treatment strategies for cognitive impairment in individuals with schizophrenia.
Section snippets
Subjects
The sample consisted of 17 inpatients with schizophrenia, diagnosed according to ICD 10 (sub-types: paranoid (n=15), hebephrenic (1), undifferentiated (1) schizophrenia). The age ranged from 22 to 44 years (median 31 years), with 7 female and 10 male patients. All patients were on stable medication with the antipsychotic amisulpride (median dose 600 mg, range between 100 and 800 mg). Four patients received a concomitant sedative medication with zolpidem (10 mg/day; two patients), diazepam (7.5
Neuropsychological test performance and results on sleep in the patients versus the controls
Patients and controls were well matched for age and years of education; the groups did not differ with respect to premorbid intelligence (see Table 1). Recall of the Rey-figure in the morning and spatial recall were significantly worse in the patients. Whereas mirror tracing in the evening did not reveal any differences between the patients and the controls, in the morning the patients made more errors than the controls at comparable velocity, with regard to procedural memory. Performance in
Discussion
The present study is the first one of its kind to investigate the interrelationship between specific measures of night sleep and performance in different aspects of memory in individuals with schizophrenia and in healthy matched controls. We hypothesized that there is an association between performance in visuospatial, primarily hippocampus-related memory and amount of SWS. Our data support this hypothesis. We found that those patients with high amounts of SWS performed significantly better in
Acknowledgements
This study was in part supported by a gift from Sanofi-Synthelabo.
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