Effects of Cigarette Smoking on Spatial Working Memory and Attentional Deficits in Schizophrenia

Sacco, Kristi A.; Termine, Angelo; Seyal, Aisha A.; Dudas, Melissa M.; Vessicchio, Jennifer C.; Krishnan‐Sarin, Suchitra; Jatlow, Peter; Wexler, Bruce E.; George, Tony P.

doi:10.1001/archpsyc.62.6.649

Cited by 319 publications

(289 citation statements)

References 70 publications

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“…The effects of nicotine on neuropsychological measures in persons with schizophrenia, unlike the effects on the P50 auditory evoked potential less are conclusive. In smokers with schizophrenia, with abstinence from nicotine, working memory is decreased [72,73]. If nicotine is then reinitiated by smoking, working memory deficits are normalized [73].…”

Section: α7 In Learning and Memorymentioning

confidence: 99%

Treating schizophrenia symptoms with an α7 nicotinic agonist, from mice to men

Olincy

Stevens

2007

Biochemical Pharmacology

125

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Current antipsychotic treatments fail to fully address the range of symptoms of schizophrenia, particularly with respect to social and occupational dysfunctions. Recent work has highlighted the role of nicotinic in both cognitive and attentional deficits as well as deficient processing of repetitive sensory information. The predilection for schizophrenia patients to be extremely heavy cigarette smokers may be related to their attempt to compensate for a reduction in hippocampal α7 nicotinic cholinergic receptors by delivering exogenous ligand to the remaining receptors. Studies in rodent models of both learning and memory deficits and deficits in sensory inhibition have confirmed a role for α7 subtype of the nicotinic cholinergic receptors in these processes. Rodent studies also demonstrated the efficacy of a selective partial α7 nicotinic agonist, DMXBA, to improve these deficits. Subsequent human clinical trials demonstrated improved sensory inhibition in 12 schizophrenia patients and showed improvement in several subtests of the RBANS learning and memory assessment instrument. These data suggest that therapeutic agents selected for α7 nicotinic activity may have utility in treating certain symptoms of schizophrenia. KeywordsSchizophrenia; nicotinic receptors; DMXBA; P50 auditory evoked potential; cognitive deficits; nicotine Although the positive symptoms such as hallucinations and delusions of schizophrenia are partially treated with the available antipsychotic medications, social and occupational dysfunction remains a major issue in treating this disorder. Cognitive deficits have been identified as more closely related to ability to adequately function [1]. In the search for new and more effective therapeutic agents for schizophrenia, recent attention has turned the nicotinic cholinergic receptors system. α7 and P50 Auditory GatingPeople with schizophrenia, in addition to the cardinal symptoms of hallucinations and delusions, suffer from the inability to focus attention. This may stem from being overwhelmed

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Section: α7 In Learning and Memorymentioning

confidence: 99%

Treating schizophrenia symptoms with an α7 nicotinic agonist, from mice to men

Olincy

Stevens

2007

Biochemical Pharmacology

125

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“…The administration of both short-and long-acting preparations of nicotine to individuals with schizophrenia has been associated with improved neuropsychological performance (Levin et al, 1996b;Depatie et al, 2002;Smith et al, 2002Smith et al, , 2006Harris et al, 2004;Jacobsen et al, 2004;Myers et al, 2004). Acute administration of the selective a7nAChR partial agonist, DMXB-A, improved P50 gating compared with placebo (Olincy et al, 2006) and administration of the nAChR antagonist, mecamylamine, blocked smoking-associated improvements in performance on attentional and visuospatial working memory (VSWM), implying that nAChR activation mediates smoking-related cognitive enhancement (Sacco et al, 2005). If nAChR activation improves cognitive dysfunction in schizophrenia, then smoking abstinence would be expected to result in deterioration in cognitive performance.…”

Section: Introductionmentioning

confidence: 99%

“…We, therefore, performed the following study to investigate the acute effects of nicotine on cognition in nonsmokers with schizophrenia and healthy controls. We selected a measure of attention as our primary outcome as the nAChR system is thought to play an integral role in the regulation of attentional processes (Mansvelder et al, 2006) and several previous studies have reported an improvement in this cognitive domain following nicotine administration in individuals with schizophrenia (Depatie et al, 2002;Harris et al, 2004;Sacco et al, 2005;Smith et al, 2006). Our primary hypothesis was that nicotine would enhance attention in nonsmokers with schizophrenia and controls; and the secondary hypothesis was that nicotine-associated improvements in cognition would be greater in the schizophrenia group compared with controls.…”

Section: Introductionmentioning

confidence: 99%

The Effects of Transdermal Nicotine on Cognition in Nonsmokers with Schizophrenia and Nonpsychiatric Controls

Barr

Culhane

Jubelt

et al. 2007

Neuropsychopharmacol

215

151

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Abundant evidence indicates that the neuronal nicotinic acetylcholine receptor (nAChR) system is integral to regulation of attentional processes and is dysregulated in schizophrenia. Nicotinic agonists may have potential for the treatment of cognitive impairment in this disease. This study investigated the effects of transdermal nicotine on attention in individuals with schizophrenia (n ¼ 28) and healthy controls (n ¼ 32). All participants were nonsmokers in order to eliminate confounding effects of nicotine withdrawal and reinstatement that may occur in the study of smokers. Subjects received 14 mg transdermal nicotine and identical placebo in a randomized, placebocontrolled, crossover design. A cognitive battery was conducted before and 3 h after each patch application. The primary outcome measure was performance on the Continuous Performance Test Identical Pairs (CPT-IP) Version. Nicotine significantly improved the performance on the CPT-IP as measured by hit reaction time, hit reaction time standard deviation and random errors in both groups. In addition, nicotine reduced commission errors on the CPT-IP and improved the performance on a Card Stroop task to a greater extent in those with schizophrenia vs controls. In summary, nicotine improved attentional performance in both groups and was associated with greater improvements in inhibition of impulsive responses in subjects with schizophrenia. These results confirm previous findings that a single dose of nicotine improves attention and suggest that nicotine may specifically improve response inhibition in nonsmokers with schizophrenia.

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“…Attentional improvement by nicotinic agents may be a key therapeutic effect for these psychiatric disorders [83,84]. It has been demonstrated that smoking withdrawal induced deficits in both attentional performance and spatial working memory in patients with schizophrenia [85]. Interestingly, these deficits are reversed with smoking and the smoking effect can be blocked by the nicotinic antagonist mecamylamine.…”

Section: The Potential Of Nicotinic Treatment For the Cognitive Impaimentioning

confidence: 99%

“…In a complementary fashion, nicotinic blockade caused significant deficits in the N-back task [91].. Nicotine nasal spray has been shown to improve spatial organization and also improve memory in people with schizophrenia [92,93]. Nicotine also improves eye tracking, memory and attentional function in schizophrenia [84,85,88,92]. Nicotine skin patch treatment in healthy volunteers significantly improved the speed of pre-attentive sensory processing as indexed by mismatch negativity to auditory stimuli in an oddball paradigm [94] Specific nicotinic receptors may be more promising for the improving aspects of cognition in people with schizophrenia .…”

Section: The Potential Of Nicotinic Treatment For the Cognitive Impaimentioning

confidence: 99%

Nicotinic interactions with antipsychotic drugs, models of schizophrenia and impacts on cognitive function

Levin

Rezvani

2007

Biochemical Pharmacology

109

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People with schizophrenia often have substantial cognitive impairments, which may be related to nicotinic receptor deficits, (α7 and α4β2), documented in the brains of people with schizophrenia. The large majority of people with schizophrenia smoke cigarettes. Thus, nicotinic interactions with antipsychotic drugs are widespread. Complementary co-therapies of novel nicotinic ligands are being developed to add to antipsychotic therapy to treat the cognitive impairment of schizophrenia. Thus, it is critical to understand the interaction between nicotinic treatments and antipsychotic drugs. Nicotinic interactions with antipsychotic drugs, are complex since both nicotine and antipsychotics have complex actions. Nicotine stimulates and desensitizes nicotinic receptors of various subtypes and potentiates the release of different neurotransmitters. Antipsychotics also act on a verity of receptor systems. For example, clozapine acts as an antagonist at a variety of neurotransmitter receptors such as those for dopamine, serotonin, norepinepherine and histamine. In a series of studies, we have found that in normally functioning rats, moderate doses of clozapine impair working memory and that clozapine blocks nicotine-induced memory and attentional improvement. Clozapine and nicotine can attenuate each other's beneficial effects in reversing the memory impairment caused by the psychototmimetic drug dizocilpine. A key to the clozapine-induced attenuation of nicotineinduced cognitive improvement appears to be its 5HT 2 antagonist properties. The selective 5HT 2 antagonist ketanserin has a similar action of blocking nicotine-induced memory and attentional improvements. It is important to consider the interactions between nicotinic and antipsychotic drugs to develop the most efficacious treatment for cognitive improvement in people with schizophrenia.

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Effects of Cigarette Smoking on Spatial Working Memory and Attentional Deficits in Schizophrenia

Cited by 319 publications

References 70 publications

Treating schizophrenia symptoms with an α7 nicotinic agonist, from mice to men

Treating schizophrenia symptoms with an α7 nicotinic agonist, from mice to men

The Effects of Transdermal Nicotine on Cognition in Nonsmokers with Schizophrenia and Nonpsychiatric Controls

Nicotinic interactions with antipsychotic drugs, models of schizophrenia and impacts on cognitive function

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