Schizophrenia and tobacco smoking comorbidity: nAChR agonists in the treatment of schizophrenia-associated cognitive deficits

Abstract

Tobacco smoking is a preventable cause of morbidity and mortality throughout the world. Very high rates of tobacco smoking are seen in patients with schizophrenia. Importantly, smokers with schizophrenia generally have higher nicotine dependence scores, experience more severe withdrawal symptoms upon smoking cessation, have lower cessation rates than healthy individuals, and suffer from significant smoking-related morbidity and premature mortality compared with the general population. Interestingly, significant disturbances in cholinergic function are reported in schizophrenia patients. The high smoking-schizophrenia comorbidity observed in schizophrenia patients may be an attempt to compensate for this cholinergic dysfunction. Cholinergic neurotransmission plays an important role in cognition and is hypothesized to play an important role in schizophrenia-associated cognitive deficits. In this review, preclinical evidence highlighting the beneficial effects of nicotine and subtype-selective nicotinic receptor agonists in schizophrenia-associated cognitive deficits, such as working memory and attention, is discussed. Furthermore, some of the challenges involved in the development of procognitive medications, particularly subtype-selective nicotinic receptor agonists, are also discussed. Amelioration of schizophrenia-associated cognitive deficits may help in the treatment of schizophrenia-smoking comorbidity by promoting smoking cessation and thus help in the better management of schizophrenia patients.

Impact of Tobacco Regulation on Animal Research: New Perspectives and Opportunities

“…Studies demonstrate nicotinic receptor antagonists worsen these symptoms (Tandon, 1999), as does smoking abstinence (George et al, 2002), with symptom improvement upon resumption of smoking behavior (Sacco et al, 2005). Furthermore, preclinical evidence points to the potential utility of nicotinic agonists for alleviating the cognitive deficits associated with schizophrenia, further highlighting how nicotine may ameliorate some symptoms (D'Souza & Markou, 2012). Smoking may also decrease medication-induced side-effects, specifically, extrapyramidal symptoms (Goff, Henderson, & Amico, 1992) that may contribute to a lack of adherence (Tandon, 2011).…”

Smoking Restores Impaired LTD-Like Plasticity in Schizophrenia: a Transcranial Direct Current Stimulation Study

“…Specifically, elevated average smoking rates 460% have been reported in patients suffering from schizophrenia (Dome et al, 2010). Different theories implicate nicotine intake via smoking as a compensatory strategy used by schizophrenia patients to ameliorate their symptoms (D'Souza and Markou, 2012).…”

“…Accordingly, postmortem studies and pharmacological challenges have reported further evidence of decreased expression levels of a 7 -nAChR in patients with schizophrenia (D'Souza and Markou, 2012;Martin-Ruiz et al, 2003). At the behavioral level, the stimulation of a 7 -nAChR through nicotine intake has been demonstrated to improve working memory and selective attention deficits, and to enhance thalamocortical functional connectivity in schizophrenia patients (Jacobsen et al, 2004;Sacco et al, 2005).…”

“…At the behavioral level, the stimulation of a 7 -nAChR through nicotine intake has been demonstrated to improve working memory and selective attention deficits, and to enhance thalamocortical functional connectivity in schizophrenia patients (Jacobsen et al, 2004;Sacco et al, 2005). Taken together, an illness-related dysfunction of corticosubcortical cholinergic networks in patients with schizophrenia, involving a complex interplay of cholinergic activation and neuroplasticity, can be assumed (D'Souza and Markou, 2012).…”

“…Despite the consistent reduction of cortical plasticity in schizophrenia patients following different types of plasticity-inducing non-invasive brain stimulation (Hasan et al, 2013a;Daskalakis et al, 2008a;Frantseva et al, 2008;Oxley et al, 2004) and the association of smoking with functional and symptomatic improvements (D'Souza and Markou, 2012), the impact of nicotine intake via smoking on neuroplasticity in schizophrenia has not yet been investigated. To determine the physiological basis of the association between nicotine and neuroplasticity, we applied LTD-like plasticity-inducing cathodal tDCS to smoking and nonsmoking schizophrenia patients.…”