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Psychopharmacology (2009) 202:259–273 DOI 10.1007/s00213-008-1302-9


Recent advances in treating cognitive impairment in schizophrenia
Cherrie Galletly

Received: 14 July 2008 / Accepted: 10 August 2008 / Published online: 3 September 2008 # Springer-Verlag 2008

Abstract Introduction Schizophrenia is often associated with chronic disability and poor outcome. In addition topositive symptoms, such as hallucinations and delusions, and negative symptoms including poverty of speech and blunted affect, schizophrenia is also associated with deficits in cognitive function. It has been increasingly recognized that the severity of cognitive impairment is a major determinant of outcome. Therefore, interventions to improve cognitive function also have the capacity to improvequality of life and social and occupational outcomes. Whilst some of the antipsychotic drugs have shown some selective benefits, there is some controversy about the extent of these benefits. Objectives This article provides an overview of research into drugs that might enhance cognition in schizophrenia. Conclusion Drugs such as modafanil and galantamine are being evaluated, and a number of new drugsare currently in development. Standardized cognitive assessment measures are being developed so studies can be compared more easily. This field is advancing rapidly, but as yet, no widely applicable, evidence-based treatments are available to the clinician. Keywords Modafanil . Galantamine . Cholinergic . Glutamate . NMDA . MATRICS . Antipsychotic . Dopamine . Neuropsychological . CNTRICSCognitive impairment in schizophrenia There is a substantial body of research describing the cognitive impairment commonly found in schizophrenia (Keefe and Fenton 2007). Deficits are evident in many domains of information processing, and it is now thought that cognitive impairment, whilst less obvious than positive symptoms such as hallucinations and delusions, may be a core component of schizophrenia.Bilder et al. (2000) found that 94 subjects with first-episode schizophrenia had a generalized deficit on neuropsychological testing of approximately 1.5 standard deviations (SD) compared to a control group. Memory showed the greatest impairment, followed by executive and motor functions. Saykin et al. (1994) compared first-episode (never medicated) and previously treated (currently unmedicated)subjects with schizophrenia. Both groups showed generalized impairment, particularly in verbal memory and learning, attention-vigilance, visual-motor processing and attention. The results of the subjects with schizophrenia were about two SD units below those of the normal controls, and the chronic group had more severe deficits. Verbal memory and learning were most impaired. Functional imagingstudies demonstrate a range of abnormalities, most consistently dorsolateral prefrontal cortex dysfunction and disrupted fronto-temporal integration (e.g. disrupted prefrontal function along with hippocampal dysfunction; Ragland et al. 2007). Schizophrenia is often regarded as a neurodevelopment disorder, and subtle cognitive deficits are apparent even in childhood (Maccabe 2008). Prospective studieshave found that children who later develop schizophrenia are more likely to be slow to learn to speak (Jones et al. 1994) and to have impaired language and arithmetic ability during childhood (Done et al. 1994). Early brain

C. Galletly (*) Discipline of Psychiatry, School of Medicine, University of Adelaide, Suite 13, The Adelaide Clinic Consulting Suites, 33 Park Tce Gilberton, Adelaide, SouthAustralia 5081, Australia e-mail: cherrie.galletly@adelaide.edu.au


Psychopharmacology (2009) 202:259–273

trauma, obstetric complications and low intelligence quotient (IQ) are risk factors for schizophrenia (David et al. 1997), indicating that vulnerability to both the psychosis and the cognitive impairment are present very early in life. There is some evidence of cognitive...
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