Neuroimaging of Smokers With and Without Attention Deficit Hyperactivity Disorder (ADHD)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate how nicotine, withdrawal from nicotine, and methylphenidate (a drug used for the treatment of ADHD) affect the brain of smokers with and without ADHD while doing tasks in an functional Magnetic Resonance Imaging scanner. Study Hypotheses: compared to non-ADHD smokers, smokers with ADHD will exhibit greater abstinence-induced decrements in response inhibition performance and reward and greater concomitant disruptions of brain activity administration of MPH to abstinent smokers will ameliorate response inhibition performance and reward deficits and task-related brain activation and this effect will be greater among ADHD smokers genetic markers of dopamine neurotransmission will moderate abstinence- and MPH - induced changes in task-related brain activation across tasks.

Detailed Description
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Individuals diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) smoke more than the general population, initiate use at a younger age, and report more difficulty trying to quit. The overarching goal of the present application is to use neuroimaging, neuropharmacological and molecular genetic techniques to study the neurobiological basis of abstinence-induced deficits in response inhibition in ADHD and non-ADHD smokers. Twenty smokers with ADHD and 20 smokers without ADHD will undergo imaging during a Go/No-Go task under the following conditions: 1) smoking as usual, 2) 24 hr smoking abstinence, and 3) 24 hr smoking abstinence + methylphenidate (MPH). We hypothesize that compared to smoking as usual, 24 hr smoking abstinence will result in decrements in response inhibition and disruption of task-related brain activation. These effects will be greater in ADHD as compared to non-ADHD smokers. We further hypothesize that MPH administration during abstinence will restore performance and brain indices of response inhibition and that the magnitude of the effect of MPH will be greater among smokers with ADHD. In addition to the above aims, we will preliminarily evaluate the moderating effects of the dopamine receptor D4 7-repeat allele on task-related brain activation following smoking abstinence and MPH administration. During the study, 101 subjects signed consents and 38 subjects completed the study.

Official Title
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Neuropharmacology of Response Inhibition in Comorbid ADHD and Nicotine Dependence

Conditions
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Smoking, ADHD

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: generally healthy, between the ages of 18-50yrs, smoking at least 10 cigarettes/day of a brand delivering ≥0.5 mg nicotine according to the standard Federal Trade Commission (FTC) method, an expired Carbon Monoxide concentration of at least 10ppm (to confirm inhalation) or a positive urine cotinine test (Nicalert ™) of 3 or greater, no interest in quitting smoking as measured by self-report, right-handed as measured by a three item scale used in our laboratory. Exclusion Criteria: unable to attend all required experimental sessions, have significant health problems (e.g., chronic hypertension, emphysema, seizure disorders, history of significant heart problems), use of psychoactive medications with the exception of ADHD pharmacotherapies among ADHD diagnosed participants (see washout procedures below) use of smokeless tobacco current or past year alcohol or drug abuse, use of illegal drugs as measured by urine drug screen or self report current use of nicotine replacement therapy or other smoking cessation treatment, presence of conditions that would make MRI unsafe (e.g., pacemaker, metal objects in the body, IUD), if they are female and pregnant or plan on becoming pregnant.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ADHD and non-ADHD Smokers<br>Those that are defined as regular smokers (10 cigarettes/day or Carbon Monoxide reading of 10 ppm). The group will then be split into those diagnosed with ADHD/ADD and controls for comparison. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effects of smoking abstinence on response inhibition brain function in smokers with and without ADHD. | Smokers will undergo three functional Magnetic Resonance Image scanning sessions while performing a task that measures response inhibition (Go/Go/No-Go task) Scanning will take place in the following conditions: smoking as usual + placebo pill, 24 hr smoking abstinence + placebo pill and 24 hr abstinence + methylphenidate (MPH). Methylphenidate is a dopamine reuptake inhibitor and its administration will allow us to evaluate the role of dopamine neurotransmission on response inhibition in the context of smoking abstinence. | July 2009 through December 2013 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Smoking, ADHD, Nicotine, Methylphenidate, function Magnetic Resonance Imaging, Neurobiological basis of abstinence-induced deficits in response inhibition