Neuropsychological deficits in individuals with an at risk mental state for psychosis — Working memory as a potential trait marker
Introduction
The early detection of psychosis and of individuals at risk for psychosis has become a well established goal within the psychiatric health care system. Risk assessment is mainly based on the presence of prodromal symptoms, self-limiting or attenuated psychotic symptoms, and a family history of psychosis in connection with deterioration in social functioning (Yung et al., 2004, Riecher-Rössler et al., 2006). But the risk assessment is not very reliable yet. Only about 20–40% of individuals identified as being at risk in fact progress to frank psychosis within a 12-month observation period (Yung et al., 2004, Riecher-Rössler et al., 2007, for review see Phillips et al., 2005).
On the other hand, studies seem to show that cognitive functioning is not only reduced in frank schizophrenia, but already in individuals with an “at risk mental state” (for review Brewer et al., 2006) and in individuals at genetic risk (for review see Niemi et al., 2003, Keshavan et al., 2005). The assessment of cognitive functioning could thus potentially enhance the predictive power of early detection of psychosis in future.
Several impaired cognitive domains associated with a prodromal state have been reported, such as impaired sustained attention, verbal and logical memory, executive functions, and spatial working memory, performance IQ, premorbid and global IQ (Brewer et al., 2005, Brewer et al., 2006). Complementary findings have recently been obtained by Niendam et al. (2006), who documented evidence for a slowing of information processing speed on the one hand and reduced motor speed on the other hand.
The results of these studies on prodromal subjects are supported by similar findings from earlier studies on subjects at risk for schizophrenia defined by genetic risk only (Cosway et al., 2000, Cornblatt et al., 1999, Reichenberg et al., 2000). Thus, cognitive functioning in relatives of schizophrenic patients showed moderate impairments in abstraction, attention, executive functions, spatial memory, sensory-motor functioning (Staal et al., 2000, Wolf et al., 2002, Erlenmeyer-Kimling et al., 2000) and impaired verbal and non-verbal intelligence, verbal logical, episodic and semantic memory, and language functions (Cosway et al., 2000, Egan et al., 2001, Byrne et al., 2003). Controversial results have been obtained with respect to sustained attention. While Cornblatt et al. (1999) documented a reduction in sustained attention only in those who later transited to psychosis, some other studies failed to provide any evidence of reduced sustained attention in individuals at genetic risk for psychosis (Cosway et al., 2002).
In summary, although there is in meantime a considerable number of studies on the neuropsychological function of individuals at risk for psychosis, only few focus on clinically defined at risk individuals in terms of a current at risk mental state respectively potential prodromal state (Brewer et al., 2006, Lencz et al., 2006, Hawkins et al., 2004, Silverstein et al., 2006, Bartok et al., 2005, Hambrecht et al., 2002). Furthermore, some of these studies so far have not thoroughly controlled for the influence of confounding variables such as age, gender, and education.
Thus, the aim of this study is to further clarify the nature and extent of neuropsychological deficits in individuals with an at risk mental state (ARMS) as compared to healthy control subjects controlling for the influence of confounding factors. The study's specific aim is to identify neuropsychological tests that provide a major contribution towards distinguishing individuals with an at risk mental state from HC.
This study is part of the Basel FePsy study (Früherkennung von Psychosen), which aims to improve the early detection of psychosis. The multi-domain assessment approach used in this study covers psychopathological, neuropsychological, neurophysiological, and neuroimaging investigations (Riecher-Rössler et al., 2007).
Section snippets
Methods
The neuropsychological data reported on here were collected within the research project “Prediction and early detection of schizophrenia — a prospective multilevel approach” at the Psychiatric Department of the University Hospital Basel, Switzerland. The study design and preliminary results of the study have been described in detail elsewhere (Riecher-Rössler et al., 2007, Gschwandtner et al., 2006, Borgwardt et al., 2006, Borgwardt et al., 2007). This report goes beyond previously published
Sample characteristics and confounding factors
Table 1 summarizes the sample characteristics of both groups. Whereas ARMS subjects were approximately four years older than the HC (p = .032), there were no significant differences between the groups concerning, gender, handedness or the number of educational years. However, ARMS subjects showed a larger variance regarding the mean number of educational years (p = .005). ARMS received significantly more often antidepressant medication than HC (p < .001). Current use of cannabis was reported by 19
Discussion
As our results show, ARMS subjects suffer from deficiencies in intelligence, executive functions and working memory compared to HC. These results where independent of whether we only analyzed the ARMS-high risk group according to the definition of Yung et al. (1998) or whether we also included 6 low risk individuals.
Regarding intelligence, our data are in line with the findings of most other authors and show a reduced intellectual capacity in ARMS subjects, especially with respect to verbal
Role of funding source
This project is supported by the Swiss National Science Foundation no. 3200-057216.99, no. 3200-057216.99 and no. PBBSB-106936, the Nora van Meeuwen-Haefliger Stiftung, Basel (CH) and by unconditional grants from the Novartis Foundation, Bristol-Myers Squibb GmbH (CH), Eli Lilly SA (CH), AstraZeneca AG (CH), Janssen-Cilag AG (CH) and Sanofi-Synthelabo AG (CH).
Contributors
Pflueger M and Gschwandtner U contributed equally to this work.
Conflict of interest
See section Role of the funding source.
Acknowledgements
We want to thank Dr. Ch. Schindler (Institute of Social and Preventive Medicine of the University of Basel) for his help with statistical analyses, Prof. Dr. G. Sachs (University Psychiatric Hospital Vienna), Dr. J. Aston, and Dr. G. Berger (both Psychiatric Department of the University Hospital Basel) for their helpful comments and all coworkers of the project for assessing the patients.
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