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

Barr, Ruth S.; Culhane, Melissa A.; Jubelt, Lindsay E.; Mufti, Rana S; Dyer, Michael A.; Weiss, Anthony P.; Deckersbach, Thilo; Kelly, John; Freudenreich, Oliver; Goff, Donald C.; Evins, A. Eden

doi:10.1038/sj.npp.1301423

Cited by 214 publications

(159 citation statements)

References 81 publications

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“…Finally, cognitive and attentional deficits are a recognized symptom class in schizophrenia [101,102,103] which can be improved with nicotine administration [104,76,77,78]. Various paradigms have been developed to assess similar learning and memory, and attention functions in rodents and similar to what is seen in humans, nicotine has been shown to improve rodent deficits in these paradigms [105,106,107,108,109].…”

Section: Dmxba As a Prototype Drugmentioning

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: Dmxba As a Prototype Drugmentioning

confidence: 99%

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

Olincy

Stevens

2007

Biochemical Pharmacology

125

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“…This heavy use of nicotine is believed to be an attempt at self-medication [120]. In controlled experiments on schizophrenia patients, nicotine has been found to enhance cognitive function [121][122][123].…”

Section: The Cholinergic System: Reversing Disinhibition and Cognitivmentioning

confidence: 99%

Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia

Lisman

Coyle

Green

et al. 2008

Trends in Neurosciences

899

818

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Many risk genes interact synergistically to produce schizophrenia and many neurotransmitter interactions have been implicated. We have developed a circuit-based framework for understanding gene and neurotransmitter interactions. NMDAR hypofunction has been implicated in schizophrenia because NMDAR antagonists reproduce symptoms of the disease. One action of antagonists is to reduce the excitation of fast-spiking interneurons, resulting in disinhibition of pyramidal cells. Overactive pyramidal cells, notably those in the hippocampus, can drive a hyperdopaminergic state that produces psychosis. Additional aspects of interneuron function can be understood in this framework, as follows. (i) In animal models, NMDAR antagonists reduce parvalbumin and GAD67, as found in schizophrenia. These changes produce further disinhibition and can be viewed as the aberrant response of a homeostatic system having a faulty activity sensor (the NMDAR). (ii) Disinhibition decreases the power of gamma oscillation and might thereby produce negative and cognitive symptoms. (iii) Nicotine enhances the output of interneurons, and might thereby contribute to its therapeutic effect in schizophrenia.

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“…Nicotine administration using 9 the NiQuitin patch generates a fast-rising nicotine plasma level (a nicotine plateau level is achieved after 2 to 4 hours after application according to the Summary of Product Characteristics of NiQuitin Clear). The 7 mg nicotine dosage was chosen as prior studies employed similar dosages and found cognitive effects in non-smokers in the absence of significant side effects (see Barr et al 2008;Levin et al 1998;Poltavski & Petros 2006). Therefore, only a low drop-out rate due to side-effects was expected.…”

Section: Experimental Design and Nicotine Applicationmentioning

confidence: 99%

Nicotine differentially modulates antisaccade performance in healthy male non-smoking volunteers stratified for low and high accuracy

et al. 2011

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RATIONALE: Nicotinergic agents are currently examined as possible pro-cognitive drugs for a variety of clinical conditions marked by cognitive deficits, such as attention deficit hyperactivity disorder (ADHD) or schizophrenia. The response to acute nicotine is heterogeneous across subjects and samples; however, only a few reliable predictors of response have been identified. OBJECTIVES: We tested the hypothesis that baseline performance level in cognitive control may be a predictor of the cognitive effects of nicotine. METHODS: We tested 28 healthy Caucasian, male, non-smoking volunteers with the antisaccade task, an oculomotor measure of cognitive control. Participants were given a 7-mg nicotine patch in a double-blind, placebo-controlled, counterbalanced, within-subjects design. Subjects were stratified into high and low performers based on their antisaccade error rate in the placebo condition (median split). RESULTS: Nicotine tended to reduce response time variability of prosaccade latency (p = 0.06). There was no main effect of nicotine on antisaccade error rate (p = 0.31). However, nicotine significantly reduced antisaccade error rate in the low-accuracy probands while leaving performance of the high-accuracy probands unaffected (interaction, p < 0.05). Furthermore, we found a nicotine-induced reduction of response time variability of antisaccade latency at one target location in the low-performing group (interaction, p < 0.05). CONCLUSIONS: The present results demonstrate the importance of baseline performance differences for the effectiveness of pharmacological enhancement of cognitive control. More generally, the results suggest that stimulation of the nicotinic acetylcholine receptor system might be an effective way of improving cognition in people with poor cognitive performance, such as patients with ADHD or schizophrenia. AbstractRationale: Nicotinergic agents are currently being examined as possible pro-cognitive drugs for a variety of clinical conditions marked by cognitive deficits, such as attention deficit hyperactivity disorder (ADHD) or schizophrenia. The response to acute nicotine is heterogeneous across subjects and samples; however, only few reliable predictors of response have been identified. Objectives:We tested the hypothesis that baseline performance level in cognitive control may be a predictor of the cognitive effects of nicotine. Methods: We tested 28 healthy Caucasian, male, non-smoking volunteers with the antisaccade task, an oculomotor measure of cognitive control.Participants were given a 7-mg nicotine patch in a double-blind, placebo-controlled, counterbalanced, within-subjects design. Subjects were stratified into high and low performers based on their antisaccade error rate in the placebo condition (median-split). Results: Nicotine tended to reduce response time variability of prosaccade latency (p=0.06). There was no main effect of nicotine on antisaccade error rate (p=0.31). However, nicotine significantly reduced antisaccade error rate in the low accuracy proban...

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

Cited by 214 publications

References 81 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

Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia

Nicotine differentially modulates antisaccade performance in healthy male non-smoking volunteers stratified for low and high accuracy

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