Background Impulsivity critically relates to many psychiatric disorders. Given the multi-faceted construct that impulsivity represents, defining core aspects of impulsivity is vital for the assessment and understanding of clinical conditions. Choice impulsivity (CI), involving the preferential selection of smaller sooner rewards over larger later rewards, represents one important type of impulsivity. Method The International Society for Research on Impulsivity (InSRI) convened to discuss the definition and assessment of CI and provide recommendations regarding measurement across species. Results Commonly used preclinical and clinical CI behavioral tasks are described, and considerations for each task are provided to guide CI task selection. Differences in assessment of CI (self-report, behavioral) and calculating CI indices (e.g., area-under-the-curve, indifference point, steepness of discounting curve) are discussed along with properties of specific behavioral tasks used in preclinical and clinical settings. Conclusions The InSRI group recommends inclusion of measures of CI in human studies examining impulsivity. Animal studies examining impulsivity should also include assessments of CI and these measures should be harmonized in accordance with human studies of the disorders being modeled in the preclinical investigations. The choice of specific CI measures to be included should be based on the goals of the study and existing preclinical and clinical literature using established CI measures.

Impulsivity is a multi-faceted construct that is a core feature of multiple psychiatric conditions and personality disorders. However, progress in understanding and treating impulsivity in the context of these conditions is limited by a lack of precision and consistency in its definition and assessment. Rapid-response-impulsivity (RRI) represents a tendency toward immediate action that occurs with diminished forethought and is out of context with the present demands of the environment. Experts from the International Society for Research on Impulsivity (InSRI) met to discuss and evaluate RRI-measures in terms of reliability, sensitivity, and validity with the goal of helping researchers and clinicians make informed decisions about the use and interpretation of findings from RRI-measures. Their recommendations are described in this manuscript. Commonly-used clinical and preclinical RRI-tasks are described, and considerations are provided to guide task selection. Tasks measuring two conceptually and neurobiologically distinct types of RRI, “refraining from action initiation” (RAI) and “stopping an ongoing action” (SOA) are described. RAI and SOA-tasks capture distinct aspects of RRI that may relate to distinct clinical outcomes. The InSRI group recommends that: 1) selection of RRI-measures should be informed by careful consideration of the strengths, limitations, and practical considerations of the available measures; 2) researchers use both RAI and SOA tasks in RRI studies to allow for direct comparison of RRI types and examination of their associations with clinically relevant measures; and, 3) similar considerations should be made for human and non-human studies in an effort to harmonize and integrate pre-clinical and clinical research.

Background The nicotine metabolite ratio (NMR or 3-hydroxycotinine/cotinine) has been used to phenotype CYP2A6-mediated nicotine metabolism. Our objectives were to analyze (a) the stability of NMR in plasma, saliva, and blood in various storage conditions, (b) the relationship between NMRs derived from blood, plasma, saliva, and urine, and (c) the reproducibility of plasma NMR in ad libitum cigarette smokers. Methods We analyzed data from four clinical studies. In studies 1 and 2, we assessed NMR stability in saliva and plasma samples at room temperature (~22°C) over 14 days and in blood at 4°C for up to 72 hours. In studies 2 and 3, we used Bland-Altman analysis to assess agreement between blood, plasma, saliva, and urine NMRs. In study 4, plasma NMR was measured on 6 occasions over 44 weeks in 43 ad libitum smokers. Results Reliability coefficients for stability tests of NMR in plasma and saliva at room temperature were 0.97 and 0.98, respectively, and 0.92 for blood at 4°C. Blood NMR agreed consistently with saliva and plasma NMRs but showed more variability in relation to urine NMR. The reliability coefficient for repeated plasma NMR measurements in smokers was 0.85. Conclusion The NMR is stable in blood, plasma, and saliva at the conditions tested. Blood, plasma, and saliva NMRs are similar while urine NMR is a good proxy for these NMR measures. Plasma NMR was reproducible over time in smokers. Impact One measurement may reliably estimate a smoker’s NMR for use as an estimate of the rate of nicotine metabolism.

There is converging evidence that certain subpopulations of smokers, such as smokers with a serious mental illness like schizophrenia (SCZ), are more likely to become addicted to tobacco and are less likely to quit smoking. This review focuses on the unique risk factors that may increase vulnerability to the initiation and maintenance of nicotine addiction in persons with schizophrenia and other psychotic disorders and also reviews the latest approaches to treating nicotine addiction and schizophrenia based on our neurobiological understanding of central nicotinic receptor systems and related neurotransmitters. In addition, suggestions for future lines of research to better understand reasons for the comorbidity of nicotine addiction in schizophrenia are discussed.

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Schizophrenia is associated with many neurocognitive deficits, some of which are improved by nicotine and cigarette smoking. To better understand the relationship between smoking and cognitive function in schizophrenia, cross-sectional assessment of neuropsychological performance as a function of smoking status (smoker or non-smoker) and smoking history (current, former or never-smoker) in clinically-stable outpatients with schizophrenia and controls was evaluated. Subjects (N=140) were divided into subgroups on the basis of self-report and biochemical verification of smoking history. Current smokers with schizophrenia (n=38), former smokers with schizophrenia (n=17), never-smokers with schizophrenia (n=12), control smokers (n=31), control former smokers (n=16), and control never-smokers (n=26) were administered a comprehensive neuropsychological battery. Smokers were studied under non-deprivation conditions. Comparison of neuropsychological performance in schizophrenia and control subjects revealed significant main effects of diagnosis. Analysis of the data as a function of smoking history demonstrated that never-smokers with schizophrenia performed the poorest on measures of sustained attention, processing speed and response inhibition, when compared to the other schizophrenia subgroups. Cigarette smoking did not alter neuropsychological performance in controls. Our findings suggest that smoking status and history differentially alters neuropsychological outcomes in schizophrenia compared to non-psychiatric controls, and that never-smokers may present with more severe neurocognitive impairments.

Positron emission tomography (PET) has convincingly provided in vivo evidence that psychoactive drugs increase dopamine (DA) levels in human brain, a feature thought critical to their reinforcing properties. Some controversy still exists concerning the role of DA in reinforcing smoking behavior and no study has explored whether smoking increases DA concentrations at the D3 receptor, speculated to have a role in nicotine's addictive potential. Here, we used PET and]oxazin-9-ol) to test the hypothesis that smoking increases DA release (decreases [ 11 C]-( þ )-PHNO binding) in D2-rich striatum and D3-rich extra-striatal regions and is related to craving, withdrawal and smoking behavior. Ten participants underwent [ 11 C]-( þ )-PHNO scans after overnight abstinence and after smoking a cigarette. Motivation to smoke (smoking topography), mood, and craving were recorded. Smoking significantly decreased self-reported craving, withdrawal, and [ 11 C]-( þ )-PHNO binding in D2 and D3-rich areas ( À 12.0 and À 15.3%, respectively). We found that motivation to smoke (puff rate) predicted magnitude of DA release in limbic striatum, and the latter was correlated with decreased craving and withdrawal symptoms. This is the first report suggesting that, in humans, DA release is increased in D3-rich areas in response to smoking. Results also support the preferential involvement of the limbic striatum in motivation to smoke, anticipation of pleasure from cigarettes and relief of withdrawal symptoms. We propose that due to the robust effect of smoking on [ 11 C]-( þ )-PHNO binding, this radiotracer represents an ideal translational tool to investigate novel therapeutic strategies targeting DA transmission.

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