The Effects of Clozapine and Risperidone on Spatial Working Memory in Schizophrenia

McGurk, Susan R.; Carter, Cameron; Goldman, Robert; Green, Michael F.; Marder, Stephen R.; Xie, Haiyi; Schooler, Nina R.; Kane, John M.

doi:10.1176/appi.ajp.162.5.1013

Cited by 74 publications

(33 citation statements)

References 19 publications

(17 reference statements)

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“…There are some reports that CLZ can significantly improve working memory dysfunctions in schizophrenic patients (e.g., Grace et al 1996;Galletly et al 1997Galletly et al , 2005Sharma et al 2003), as opposed to several findings reporting no or even detrimental effects of chronic CLZ treatment on working memory performance in affected individuals (e.g., Hagger et al 1993;Lee et al 1999;Adler et al 2002;McGurk et al 2005). While there has been a long discussion on the involvement of hippocampal dysfunctions in the neuropathology and pathophysiology of schizophrenia (Harrison 1999(Harrison , 2004Weinberger 1999;Antonova et al 2004;Tamminga 2006), the nature and/or severity of hippocampal abnormalities are likely to differ considerably between individual subjects suffering from this disorder.…”

Section: Discussionmentioning

confidence: 99%

Chronic clozapine treatment improves prenatal infection-induced working memory deficits without influencing adult hippocampal neurogenesis

et al. 2009

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Section: Discussionmentioning

confidence: 99%

Chronic clozapine treatment improves prenatal infection-induced working memory deficits without influencing adult hippocampal neurogenesis

et al. 2009

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“…Though some studies report a beneficial effect (McGurk et al, 2005), we previously reported in two independent samples a worsening of spatial working memory on an oculomotor-delayed response (ODR) task after risperidone treatment (Reilly et al, , 2007. The ODR task places heavier demands on maintenance rather than manipulation aspects of working memory compared to most neuropsychological tests, and therefore it is more similar in cognitive demand to the requirements of the predictive saccade task.…”

Section: Spatial Working Memorymentioning

confidence: 90%

Effects of Risperidone on Procedural Learning in Antipsychotic-Naive First-Episode Schizophrenia

Harris

Wiseman

Reilly

et al. 2008

Neuropsychopharmacol

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Studies of procedural learning in medicated schizophrenia patients using predictive saccade paradigms have consistently demonstrated hypometric predictive responses. Findings from antipsychotic-naive schizophrenia patients indicate fewer or no deficits. This pattern of findings suggests that antipsychotic medications might adversely affect frontostriatal systems supporting procedural learning on this task. The accuracy and latency of predictive saccades were assessed in 25 antipsychotic-naive first-episode schizophrenia patients and 22 matched healthy individuals. Patients were retested after 6 weeks of treatment with risperidone. Healthy individuals were reevaluated after a similar time period. The ability to learn to time response initiation in anticipation of target appearance (target prediction) was not impaired in patients before or after treatment. In contrast, although no deficits were evident before treatment initiation, after treatment patients showed a marked decrease in the accuracy of predictive but not sensory-guided responses. The findings from pretreatment testing indicate that procedural learning is a relatively unaffected cognitive domain in antipsychotic-naive first-episode schizophrenia. Although treatment-emergent extrapyramidal symptoms were minimal, these data suggest that D2 antagonism in striatum after risperidone treatment was sufficiently robust to disrupt the generation of planned volitional behavior guided by internalized representations.

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“…In a more recent study, risperidone was found to improve spatial working memory compared with haloperidol; however, this superiority was eliminated when the confounding effects of the anticholinergic benztropine (administered adjunctively with haloperidol) were considered (McGurk et al, 2004). Other studies in subjects with schizophrenia have documented both improvements (McGurk et al, 2005) and impairments (Reilly et al, 2006) in spatial working memory associated with long-term risperidone treatment. The clinical effects of antipsychotics on sustained attention also appear to be equivocal.…”

Section: Discussionmentioning

confidence: 95%

Differential Long-Term Effects of Haloperidol and Risperidone on the Acquisition and Performance of Tasks of Spatial Working and Short-Term Memory and Sustained Attention in Rats

Hutchings

Waller

Terry

2013

J Pharmacol Exp Ther

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A common feature of the neuropsychiatric disorders for which antipsychotic drugs are prescribed is cognitive dysfunction, yet the effects of long-term antipsychotic treatment on cognition are largely unknown. In the current study, we evaluated the effects of long-term oral treatment with the first-generation antipsychotic haloperidol (1.0 and 2.0 mg/kg daily) and the secondgeneration antipsychotic risperidone (1.25 and 2.5 mg/kg daily) on the acquisition and performance of two radial-arm maze (RAM) tasks and a five-choice serial reaction-time task (5C-SRTT) in rats during days 15-60 and 84-320 days of treatment, respectively. In the RAM, neither antipsychotic significantly affected the acquisition or performance of a spatial win shift or a delayed non-match-to-position task. Conversely, in the rats administered 5C-SRTT, haloperidol was associated with profound deficits in performance, and the subjects were not able to progress through all stages of task acquisition. Depending on the dose, risperidone was associated with a greater number of trials to meet specific performance criteria during task acquisition compared with vehicle-treated controls; however, most subjects were eventually able to achieve all levels of task acquisition. Both haloperidol and risperidone also increased the number of perseverative and time-out responses during certain stages of task acquisition, and the response and reward latencies were slightly higher than controls during several stages of the study. These results in rats suggest that while long-term treatment with haloperidol or risperidone may not significantly affect spatial working or short-term memory, both antipsychotics can (depending on dose) impair sustained attention, decrease psychomotor speed, increase compulsivetype behaviors, and impair cognitive flexibility.

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The Effects of Clozapine and Risperidone on Spatial Working Memory in Schizophrenia

Abstract: The differential effects of these medications on spatial working memory may be due to the anticholinergic effects of clozapine and prefrontal dopamine-enhancing effects of risperidone.

Cited by 74 publications

References 19 publications

Chronic clozapine treatment improves prenatal infection-induced working memory deficits without influencing adult hippocampal neurogenesis

Chronic clozapine treatment improves prenatal infection-induced working memory deficits without influencing adult hippocampal neurogenesis

Effects of Risperidone on Procedural Learning in Antipsychotic-Naive First-Episode Schizophrenia

Differential Long-Term Effects of Haloperidol and Risperidone on the Acquisition and Performance of Tasks of Spatial Working and Short-Term Memory and Sustained Attention in Rats

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