Executive function in schizophrenia: what impact do antipsychotics have?

Abstract

Cognitive dysfunction is a major component of schizophrenia, with deficits in executive function particularly pertinent to successful daily living and outcome. Executive deficits and negative/disorganised symptoms remain relatively resistant to amelioration by antipsychotic medication in comparison to positive symptoms. While there is a relative paucity of data on the effects of antipsychotics on specific executive deficits, atypical antipsychotics would appear to be more beneficial than typical antipsychotics at improving these functions, with muscarinic, glutamatergic and cholinergic systems variously implicated. Recent research focusing on the relationships between specific symptoms and specific executive deficits holds important implications for future psychopharmacological interventions in the area by elucidating the neural substrates and pathways which underpin schizophrenic symptomatology. This review attempts to evaluate the research thus far for the specific executive components of spatial working memory (SWM), inhibition, sustained attention and set shifting. Issues significant to future psychopharmacology in the area are discussed, with particular emphasis on the need for a greater consensus in methodology and definition executive function research in schizophrenia.

Effects of asenapine, olanzapine, and risperidone on psychotomimetic-induced reversal-learning deficits in the rat

“…These same agents demonstrate some efficacy in improving neurocognition in patients with schizophrenia [14,32]. It is of interest to note that although antipsychotics have demonstrated cognitiveenhancing effects in patients with schizophrenia, the effects have generally been found to be small and inadequate [17,32,42], whereas effects in animal models have been more consistent and more pronounced. The reasons for discrepancies between cognitive efficacy in patients with schizophrenia and animal models are not fully understood.…”

“…However, the clinical literature has generally reported no consistent, substantial improvement in cognition with the current pharmacotherapies for schizophrenia [20,42]. In one long-term naturalistic study, the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, some antipsychotics produced small but statistically significant improvements in cognition [32].…”

Animal models of cognitive dysfunction and negative symptoms of schizophrenia: Focus on NMDA receptor antagonism

“…Attention is a multi-faceted system that allows an individual to detect, select and process relevant stimuli, while simultaneously filtering out irrelevant stimuli from the surrounding environment. Executive functioning, which includes abstract problem solving and behavioural inhibition, is often described as a system of higher-order cognitive processing that allows the individual to plan and execute goal-specific behaviours (Velligan & Bow-Thomas, 1999;O'Grada & Dinan, 2007). Many tasks have been developed to assess these aspects of cognitive ability in the clinic and include tests such as the Continuous Performance Task (CPT) and the Wisconsin Card Sorting Task (WCST) (Rosvold et al, 1956;Cornblatt & Keilp, 1994;Weisbrod et al, 2000).…”

Effect of sertindole on extracellular dopamine, acetylcholine, and glutamate in the medial prefrontal cortex of conscious rats: a comparison with risperidone and exploration of mechanisms involved

“…Moreover, current antipsychotics have the ability to block dopamine (DA) D 2 receptors to a varying degree at therapeutically relevant doses (Talbot and Laruelle 2002). While conventional D 2 receptor-blocking antipsychotics primarily have clinical effect on positive symptoms of schizophrenia, the second-generation antipsychotics, which have a broader receptor profile, seem to have some beneficial effects on negative symptoms and moderate effects on cognitive deficits as well (Meltzer and McGurk 1999;O'Grada and Dinan 2007;Pratt et al 2008;Remington and Kapur 2000). The additional 5-HT 2A receptor antagonistic property of some second-generation antipsychotics is assumed to be involved in their therapeutic mechanism of action (Wood et al 2006).…”