The potential of nicotinic enhancement of cognitive remediation training in schizophrenia

Hahn, Britta; Gold, James M.; Boyer, Robert

doi:10.1016/j.neuropharm.2012.05.050

Cited by 16 publications

(11 citation statements)

References 119 publications

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“…Attention-enhancing effects of transdermal nicotine were robust in SCZ and HCS. nAChR agonists given via a delivery system with similar temporal stability may improve everyday functioning in SCZ, especially long-term when coupled with cognitive challenges inherent in daily life or induced by training interventions(62). Although attention-enhancing effects of nicotine are likely not the primary driving force of tobacco consumption in SCZ, these effects may have therapeutic benefits when optimally harvested.…”

Section: Discussionmentioning

confidence: 99%

A Test of the Cognitive Self-Medication Hypothesis of Tobacco Smoking in Schizophrenia

Hahn

Harvey

Concheiro

et al. 2013

Biological Psychiatry

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Background Heavier tobacco smoking among people with schizophrenia (SCZ) has been suggested to reflect self-medication of cognitive deficits. The idea that cognitive-enhancing effects of nicotine are a primary motivator of tobacco consumption in SCZ and that abstinence would deprive SCZ of such beneficial effects may explain hesitation among providers to pursue smoking cessation in SCZ. This study tested predictions of the cognitive self-medication hypothesis. Methods In three counterbalanced sessions, 17 SCZ and 17 healthy control subjects (HCS), all smokers, were tested under ad libitum smoking, or 3.5 hours after abstaining and receiving a nicotine (14 mg/24 hrs) or placebo patch. Results Attention task performance was improved by transdermal nicotine relative to placebo, with intermediate performance by ad libitum smoking. These effects were of similar size in SCZ and HCS, and did not reflect remediation of functions disproportionately impaired in SCZ. Although more SCZ reported that the need to concentrate influenced their smoking, this was not reflected by these patients' actual behavior. Self-reported ability to concentrate changed with nicotine status in HCS but not SCZ, suggesting insensitivity of SCZ to nicotine-derived performance benefits. Nicotine plasma concentrations after ad libitum smoking were not associated with performance benefits but instead with the propensity to experience nicotine withdrawal upon abstinence. This association was seen selectively in SCZ, suggesting a possible reason for heavier smoking. Conclusions These findings suggest that subjective or objective attentional benefits are unlikely the primary driving force of tobacco consumption in SCZ and should not discourage providers from supporting quit attempts.

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Section: Discussionmentioning

confidence: 99%

A Test of the Cognitive Self-Medication Hypothesis of Tobacco Smoking in Schizophrenia

Hahn

Harvey

Concheiro

et al. 2013

Biological Psychiatry

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“…via α6β2 nAChR activation [197]. Nicotinic treatments may also need to be tested as more than simple add-ons to antipsychotic treatment to improve cognition alone, but possibly also as augmentation treatments to cognitive training therapies [198, 199]. In fact, given the putative role of the α7 nAChR in reward-associative learning and the use of positive feedback during such cognitive training, treatments targeted at this receptor may be ideal for augmenting cognitive training [192]…”

Section: Conclusion and Recommendations For Future Directionsmentioning

confidence: 99%

Evaluating the role of the alpha-7 nicotinic acetylcholine receptor in the pathophysiology and treatment of schizophrenia

Young

Geyer

2013

Biochemical Pharmacology

114

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The group of schizophrenia disorders affects approximately 1% of the population and has both genetic and environmental etiologies. Sufferers report various behavioral abnormalities including hallucinations and delusions (positive symptoms), reduced joy and amotivation (negative symptoms), plus inattention and poor learning (cognitive deficits). Despite the heterogeneous symptoms experienced, most patients smoke. The self-medication hypothesis posits that patients smoke to alleviate symptoms, consistent with evidence for nicotine-induced enhancement of cognition. While nicotine acts on multiple nicotinic acetylcholine receptors (nAChRs), the primary target of research is often the homomeric α7 nAChR. Given genetic linkages between schizophrenia and this receptor, its association with P50 sensory gating deficits, and its reduced expression in post-mortem brains, many have attempted to develop α7 nAChR ligands for treating schizophrenia. Recent evidence that ligands can be orthosteric agonists or positive allosteric modulators (PAMs) has revitalized the hope for treatment discovery. Herein, we present evidence regarding: 1) Pathophysiological alterations of α7 nAChRs that might occur in patients; 2) Mechanistic evidence for the normal action of α7 nAChRs; 3) Preclinical studies using α7 nAChR orthosteric agonists and type I/II PAMs; and 4) Where successful translational testing has occurred for particular compounds, detailing what is still required. We report that the accumulating evidence is positive, but that greater work is required using positron emission tomography to understand current alterations in α7 nAChR expression and their relationship to symptoms. Finally, cross-species behavioral tasks should be used more regularly to determine the predictive efficacy of treatments.

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“…Such drugs augment cognition among cigarette smokers, nonsmokers, and neuropsychiatric patients (2-6) suggesting facilitation beyond nicotine withdrawal reversal. Accordingly, nAChR agonists may provide a productive area of drug development for not only nicotine addiction (7), but also cognitive enhancement when considering healthy individuals (8) and neuropsychiatric conditions such as schizophrenia (9) or attention deficit hyperactivity disorder (10). At the cellular-level, nAChR agonists modulate neuronal activity directly by depolarizing the cell and/or indirectly by altering presynaptic neurotransmission (11-13).…”

Section: Introductionmentioning

confidence: 99%

Neurobiological Impact of Nicotinic Acetylcholine Receptor Agonists: An Activation Likelihood Estimation Meta-Analysis of Pharmacologic Neuroimaging Studies

Sutherland

Ray

Riedel

et al. 2015

Biological Psychiatry

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Background Nicotinic acetylcholine receptor (nAChR) agonists augment cognition among cigarette smokers and nonsmokers, yet the systems-level neurobiological mechanisms underlying such improvements are not fully understood. Aggregating neuroimaging results regarding nAChR agonists provides a means to identify common functional brain changes that may be related to pro-cognitive drug effects. Methods We conducted a meta-analysis of pharmacological neuroimaging studies within the activation likelihood estimation framework. We identified published studies contrasting a nAChR drug condition versus a baseline and coded each contrast by activity change direction (decrease or increase), participant characteristics (smokers or nonsmokers), and drug manipulation employed (pharmacological administration or cigarette smoking). Results When considering all studies, nAChR agonist administration was associated with activity decreases in multiple regions, including the ventromedial prefrontal cortex (vmPFC), posterior cingulate cortex (PCC), parahippocampus, insula, and the parietal and precentral cortices. Conversely, activity increases were observed in lateral frontoparietal cortices, the anterior cingulate cortex (ACC), thalamus, and cuneus. Exploratory analyses indicated that both smokers and nonsmokers showed activity decreases in the vmPFC and PCC, and increases in lateral frontoparietal regions. Among smokers, both pharmacological administration and cigarette smoking were associated with activity decreases in the vmPFC, PCC, and insula, and increases in the lateral PFC, dorsal ACC, thalamus, and cuneus. Conclusions These results provide support for the systems-level perspective that nAChR agonists suppress activity in default-mode network regions and enhance activity in executive control network regions in addition to reducing activation of some task-related regions. We speculate these are potential mechanisms by which nAChR agonists enhance cognition.

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The potential of nicotinic enhancement of cognitive remediation training in schizophrenia

Cited by 16 publications

References 119 publications

A Test of the Cognitive Self-Medication Hypothesis of Tobacco Smoking in Schizophrenia

A Test of the Cognitive Self-Medication Hypothesis of Tobacco Smoking in Schizophrenia

Evaluating the role of the alpha-7 nicotinic acetylcholine receptor in the pathophysiology and treatment of schizophrenia

Neurobiological Impact of Nicotinic Acetylcholine Receptor Agonists: An Activation Likelihood Estimation Meta-Analysis of Pharmacologic Neuroimaging Studies

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