Cognitive dysfunction in schizophrenia

Friedman JI, Adler DN, Davis KL (1999) The role of norepinephrine in the pathophysiology of cognitive disorders potential applications to the treatment of cognitive dysfunction in schizophrenia and Alzheimer s disease. Biol. Psychiatry 46 1243-1252. 

Castner SA, Goldman-Rakic PS, Williams GV. Animal models of working memory insights for targeting cognitive dysfunction in schizophrenia. Psychopharmacology 2004 174 111-125. 

Waddington, J. L., O Callaghan, E., Larkin, C., Kinsella, A. 1993, Cognitive dysfunction in schizophrenia organic vulnerability factor or state marker for tardive dyskinesia , Brain Cogn., vol. 23, no. 1, pp. 56-70. 

Krausz, M., Moritz, S., Naber, D., Lambert, M., Andresen, B. (1999). Neuroleptic-induced extrapyramidal symptoms are accompanied by cognitive dysfunction in schizophrenia. European Psychiatry, 14, 84-88. 

Ferreri F, Agbokou C, Gauthier S. 2006. Cognitive dysfunctions in schizophrenia Potential benefits of cholinesterase inhibitor adjunctive therapy. J Psychiatry Neurosci 31 ... 

Lewis DA, Moghaddam B. 2006. Cognitive dysfunction in schizophrenia Convergence of gamma-aminobutyric acid and glutamate alterations. Arch Neurol 63 1372-1376. 

Sawada K, Barr AM, Nakamura M, Arima K, Young CE, et al. 2005. Hippocampal complexin proteins and cognitive dysfunction in schizophrenia. Arch Gen Psychiatry 62 ... 

Lewis DA, Cruz D, Eggan S, Erickson S. 2004. Postnatal development of prefrontal inhibitory circuits and the pathophysiology of cognitive dysfunction in schizophrenia. Ann NY Acad Sci 1021 64-76. 

The deficit of cortico-striatal innervation that is presumably responsible for reported losses of striatal glutamate uptake sites (Aparicio-Legarza et al., 1997 Simpson et al., 1992), is likely to contribute to the cognitive dysfunction of schizophrenia. These have been described as having similarities to the subcortical dementia (Pantelis et al., 1992) seen in a variety of neurodegenerative disorders disturbances of corticostriatal function are thought to underlie this pattern of cognitive deficits that include disturbances of attention, executive function and short-term memory. 

Glutamate was initially implicated in schizophrenia by studies of the behavioral effects of N-methyl-D-aspartate (NMDA) receptor antagonists (e.g., PCP, ketamine), which produce psychotic symptoms and cognitive dysfunction in healthy subjects and exacerbate psychotic, negative, and cognitive symptoms in patients with schizophrenia. Studies show that acute administration of NMDA antagonists causes NMDA receptor dysfunction, resulting in decreased inhibition of subcortical dopamine neurons and consequent increased mesolimbic dopamine release. Chronic administration produces decreased release, or hypoactivity, of dopamine in the prefrontal cortex (Davis and Lieberman, 2000). 

Taken together, the evidence for a specific deficit of hippocampal interneurons is accumulating. Together with the neuroimaging findings, this pattern points to a disinhibition of hippocampal pyramidal cells in schizophrenia. Future studies will explore the molecular mechanisms of hippocampal dysfunction in schizophrenia and it s impact on the cognitive and social function in schizophrenia. 

Poyurovsky. M., Korcn, D., Gonopolsky, I.. Schneidman. M., Fuchs, C Weizman, A., and Weizman, R. (2003). Effect of the 5-HTt antagonist mianserin on cognitive dysfunction in chronic schizophrenia patients An add-on, double-blind placebo-control led study. Ear. Neuropsychopharmacol. 13, 123-128. 

A basic ethical issue in several areas of psychiatric research is whether participants are able to provide informed consent, particularly for protocols entailing medication washout and/or placebo treatment. The majority of psychiatric patients who are asked to participate in clinical trials have adequate capacity to provide consent. Thus, in a study specifically designed to examine the capacity of schizophrenic patients to give informed consent, cognitive dysfunction and negative symptoms (apathy and avolition). but not psychotic symptoms (hallucinations, delusions), were found to be associated with impaired decisional capacity (Moser et al., 2002). These features are probably not unique to schizophrenia but are likely to apply to many other forms of illness. 

Schizophrenia is certainly not the only disorder with such impairments in cognition. Autism, poststroke dementia, Alzheimer s disease, and many other organic dementias (parkinsonian/Lewy body dementia, frontotemporal/Pick s dementia, etc.) are also associated with some cognitive dysfunctions similar to those seen in schizophrenia (Fig. 10—4). 

Goldman-Rakic PS, Castner SA, Svensoon IH, Siever LJ, Williams GV Targeting the dopamine D1 receptor in schizophrenia insights for cognitive dysfunction. Psychopharmacology 2004 174 3-16. 

In addition to Wilson et al. (1983), several other studies reported an association between TD symptoms and generalized mental dysfunction (Baribeau et al., 1993 DeWolfe et al., 1988 Itil et al., 1981 Spohn et al., 1993 Struve et al., 1983 Waddington et al., 1986a b Wolf et al., 1982 many reviewed in Breggin, 1993). After eliminating schizophrenia as a causative factor, Waddington and Youssef (1988) also found increased cognitive deficits in neuroleptic-treated bipolar patients with TD in comparison to those without the disorder. 

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