Antipsychotic Drugs Exacerbate Impairment on a Working Memory Task in First-Episode Schizophrenia

Reilly, James L.; Harris, Margret S.H.; Khine, Tin; Keshavan, Matcheri S.; Sweeney, John A.

doi:10.1016/j.biopsych.2006.10.031

Cited by 85 publications

(54 citation statements)

References 15 publications

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“…These findings are consistent with those observed with several larger clinical trials using neuropsychological measures that sought to compare different medication effects on cognitive outcomes. 60,61 In contrast, on several oculomotor tasks, we found changes after antipsychotic treatment that exceeded practice effects observed in healthy individuals who were studied in parallel and that suggested improvement in aspects of automatic and voluntary attentional control, 54,55 and a worsening of working memory performance 57,58 similar to effects observed in nonhuman primates exposed to antipsychotic drugs. 62 Thus, a pattern of both beneficial and adverse treatment-related effects were observed on oculomotor performance measures.…”

Section: The Generalized Deficit and Evaluation Of Pharmacological Trmentioning

confidence: 63%

Generalized and Specific Neurocognitive Deficits in Psychotic Disorders: Utility for Evaluating Pharmacological Treatment Effects and as Intermediate Phenotypes for Gene Discovery

Reilly

Sweeney

2014

Schizophrenia Bulletin

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A growing body of research suggests that schizophrenia and bipolar disorder share overlapping clinical, neurobiological, and genetic features, raising important questions about the boundaries and distinctiveness of these 2 major psychiatric disorders. A generalized cognitive impairment has long been understood to be a core feature of schizophrenia. More recently, it has become apparent that cognitive impairment also occurs in bipolar disorder, particularly in those patients with a history of psychotic symptoms. Whether a generalized deficit exists across a spectrum of psychotic disorders is less clearly established. Additionally, in the context of a broad impairment, it remains a significant challenge to identify deficits in specific cognitive processes that may have distinct neurochemical or regional brain substrates and linkages to particular risk-associated genetic factors. In this article, we review the findings from neuropsychological studies across a spectrum that includes schizophrenia, schizoaffective and bipolar disorders, and conclude the available evidence strongly supports that a generalized deficit is present across psychotic disorders that differs in severity more so than form. We then consider the implications of generalized and specific deficits in psychosis for 2 areas of research-the evaluation of pharmacological treatments targeting cognitive deficits, and the investigation of cognitive intermediate phenotypes in family genetic studies. Examples from the literature that touch on the relevance of the generalized deficit in these contexts are provided, as well as consideration for the continued need to identify specific impairments that are separable from the generalized deficit in order to advance drug and gene discovery.

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Section: The Generalized Deficit and Evaluation Of Pharmacological Trmentioning

confidence: 63%

Generalized and Specific Neurocognitive Deficits in Psychotic Disorders: Utility for Evaluating Pharmacological Treatment Effects and as Intermediate Phenotypes for Gene Discovery

Reilly

Sweeney

2014

Schizophrenia Bulletin

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“…[87][88][89][90] The significant reduction of gray matter volume in PFC in schizophrenia may contribute an anatomical basis to such underactivations in patients with NN-FES and may help to explain their impaired ability to encode information into working memory, even at an early stage of the illness. 86,91 Frontal volumetric abnormalities were also observed in the treated group and might be related to the eventual development of negative symptoms, also unresponsive to drug treatment and characteristically associated with smaller frontal volume. 92,93 Indeed, rather than a ''reversal'' of volume deficits following drug treatment, subtraction analysis revealed significantly more extensive gray matter volume deficits in bilateral medial frontal and inferior frontal gyrus in NT-FES compared with NN-FES.…”

Section: Discussionmentioning

confidence: 98%

“…Similarly, longitudinal functional studies before and after 6 weeks of atypical treatment in NN-FES have found that pretreatment cognitive deficits are exacerbated by antipsychotics. 86,91 The authors suggested that this adverse cognitive effect of antipsychotics might be related to changes in prefrontal dopaminergic systems particularly the D1 receptor system. Even 4 weeks of atypical treatment did not improve hypoactivation in dorso-lateral prefrontal cortex in FES.…”

Section: Discussionmentioning

confidence: 99%

Gray Matter in First-Episode Schizophrenia Before and After Antipsychotic Drug Treatment. Anatomical Likelihood Estimation Meta-analyses With Sample Size Weighting

Leung

Cheung

et al. 2009

Schizophrenia Bulletin

122

102

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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: 92%

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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Antipsychotic Drugs Exacerbate Impairment on a Working Memory Task in First-Episode Schizophrenia

Cited by 85 publications

References 15 publications

Generalized and Specific Neurocognitive Deficits in Psychotic Disorders: Utility for Evaluating Pharmacological Treatment Effects and as Intermediate Phenotypes for Gene Discovery

Generalized and Specific Neurocognitive Deficits in Psychotic Disorders: Utility for Evaluating Pharmacological Treatment Effects and as Intermediate Phenotypes for Gene Discovery

Gray Matter in First-Episode Schizophrenia Before and After Antipsychotic Drug Treatment. Anatomical Likelihood Estimation Meta-analyses With Sample Size Weighting

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

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