Regional Differences in the Action of Antipsychotic Drugs: Implications for Cognitive Effects in Schizophrenic Patients

Abstract

Antipsychotic drugs (APDs) have been classified as typical or atypical based on their liability to produce extrapyramidal side effects: atypical APDs are less likely to produce extrapyamidal side effects at therapeutic doses. Evidence from immediate early gene immunohistochemical, electrophysiological, microdialysis, imaging, and behavioral studies suggests that typical APDs preferentially affect the nucleus accumbens (NAc) and the dorsal striatum while atypical APDs preferentially affect the NAc and medial prefrontal cortex (PFC). We review some of this evidence and then discuss studies that have employed cognitive tasks shown previously to depend on dorsal striatal or medial PFC function in schizophrenic patients treated with typical or atypical APDs. Results revealed that patients treated with typical APDs displayed deficits in cognitive tasks that depended on the dorsal striatum but not in tasks that depended on the medial PFC and that those treated with atypical APDs displayed deficits in cognitive tasks that depended on the medial PFC but not in cognitive tasks that depended on the dorsal striatum. These findings suggest that some of the cognitive deficits seen in schizophrenic patients may be related to the medications that are used to treat them.

Cognitive differences in schizophrenia on long-term treatments with clozapine, risperidone and typical antipsychotics

“…These results are supported by other studies (Beninger et al, 2010;Hill et al, 2010;Terry and Mahadik, 2007). Though this study was cross-sectional design, it was random and therefore might provide robust evidence that APDs may influence cognition in patients with chronic schizophrenia on long-term medication.…”

“…Previous studies have shown that cognitive function in patients with schizophrenia could be influenced by APDs (Beninger et al, 2010;Terry and Mahadik, 2007). For example, some studies have suggested that APDs induce distinct regionalized neural responses in different brain regions that are associated with distinct cognitive functions (Beninger et al, 2010;Westerink, 2002).…”

“…For example, some studies have suggested that APDs induce distinct regionalized neural responses in different brain regions that are associated with distinct cognitive functions (Beninger et al, 2010;Westerink, 2002). Moreover, some studies have shown that APDs, in particular atypical APDs, are associated with the improvement in some cognitive deficits in patients with schizophrenia, especially executive function, spatial memory, processing speed, and attention (Hill et al, 2010;Keefe et al, 2006;Meltzer and McGurk, 1999;Woodward et al, 2005).…”

Clozapine-Induced Locomotor Suppression is Mediated by 5-HT2A Receptors in the Forebrain

“…Clozapine has been shown to bind upwards of 50 receptor targets in vitro (Roth et al, 2004) showing strong affinity for dopaminergic, serotonergic, muscarinic, adrenergic, and histaminergic receptors; however, the full spectrum of its in vivo receptor affinity is subject to some discussion (Beninger et al, 2010;Coward, 1992;McCormick et al, 2010;Roth et al, 2004;Schotte et al, 1993). Although it pioneered second-generation drugs, which have lower liability to cause EPS and tardive dyskinesias, these compounds are hampered by side effects such as weight gain, hyperlipidemia, agranulocytosis, and sedation.…”

Translating Neurobiology to the Treatment of Dual Diagnosis: The Example of Nicotinic Receptors and Neurocognitive Endophenotypes in Schizophrenia

“…However, some recent studies do not support the use of antipsychotic medication in alleviating cognitive dysfunction in these patients [47,48]. Clearly, more specific research in this domain is required, and studies should separate smoking and non-smoking groups of patients to parse out the contribution of nAChR activation on cognition.…”