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It has been suggested that patients with schizophrenia smoke in order to produce amelioration of dysfunctional dopaminergic pathways allowing them to experience pleasure and satisfaction and overcome anhedonia. No studies have assessed the effects of nicotine withdrawal on reward responsivity in patients with schizophrenia. The investigators believe that an understanding of this is crucial if improved treatments for nicotine dependence are to be developed for this patient population. If this group already has deficits in reward responsivity as a symptom of the disease then they may be particularly prone to the effects of nicotine withdrawal on reward systems. Smoking cessation may lead to a further decrease in their responsivity to pleasurable stimuli and worsening anhedonia. Treatments for smoking cessation may need to ameliorate any increased deficits if they are likely to be effective in patients with schizophrenia.
Heavy smoking continues to represent a significant public health problem for people in the general population and for people with major mental illness. Twenty-four percent of adults in the general population smoke and it has been estimated that 74-92% of people with schizophrenia smoke. While effective treatments for smoking cessation have been developed, response rates are modest and relapse rates are high. Approximately 70% of people who quit smoking with effective treatments relapse to smoking within one year. A syndrome of negative affect and anhedonia has been described as an important component in maintenance of dependence on nicotine. It has also been suggested that preventing the syndrome of anhedonia and negative affect during early abstinence may reduce relapse rates. If the syndrome of anhedonia can be measured objectively and quantitatively, we will be better able to test treatments for this withdrawal syndrome. It is our hypothesis that the syndrome of anhedonia during early abstinence from nicotine is quantifiable as a deficit in reward responsivity.
Animal studies suggest that nicotine withdrawal is associated with an alteration in reward responsivity. Brain stimulation reward thresholds have been used to measure anhedonia and responsivity to reward in animal models. Nicotine withdrawal has been associated with a significant decrease in brain reward function as measured by elevations in brain reward thresholds that persist for 4 days. Nicotine withdrawal has also been associated with failure of conditioning to an environment paired with novel stimuli, possibly due to a decrease in reward associated with novel stimuli. Drug withdrawal states have also been associated with inhibition of mesolimbic release in murine models.
We propose a randomized placebo controlled trial to investigate the effects of nicotine abstinence on reward responsivity in patients with no major mental illness and in patients with schizophrenia.
Aim 1: To evaluate the effects of nicotine withdrawal on a measure of reward responsivity Hypothesis 1a: Normal controls and subjects with schizophrenia will demonstrate deterioration on a measure of reward responsivity during abstinence (placebo condition) compared to baseline. (Primary Outcome Measure)
Aim 2: To evaluate the effects of transdermal nicotine on reward responsivity during abstinence.
Hypothesis 2a: Normal controls and subjects with schizophrenia will demonstrate greater response bias toward a rewarded condition following transdermal nicotine administration relative to placebo patch during a 3 day period of abstinence.
Aim 3: To evaluate the effects of smoking abstinence and transdermal nicotine on a measure of reward responsivity in patients with schizophrenia who smoke relative to normal control smokers.
Hypothesis 3a: Subjects with schizophrenia will demonstrate decreased reward responsivity during all conditions (baseline, nicotine replacement therapy condition and placebo condition) relative to normal controls.
Aim 4: To evaluate the effects of nicotine withdrawal on cognitive function in smokers Hypothesis 4a: Normal controls and subjects with schizophrenia will demonstrate poorer performance on tests of cognition following placebo administration compared with baseline and nicotine conditions.
We propose to test the effects of smoking abstinence and nicotine replacement therapy, using nicotine transdermal patch on a measure of reward responsivity in patients who smoke. We propose a randomized placebo controlled crossover trial with the primary outcome measure being Response bias using a signal detection task.
Subjects are 70 patients with schizophrenia who smoke and 70 normal control smokers who do not have a major mental illness and who are matched for age, sex and nicotine dependence. Though we expect to consent 70 subjects in each group, we expect only 20 subjects in each group to complete the study
Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Treatment
transdermal nicotine patch
Freedom Trail Clinic, 25 Staniford Street
North Suffolk Mental Health Association
Published on BioPortfolio: 2014-08-27T03:42:41-0400
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A medicated adhesive patch placed on the skin to deliver a specific dose of medication into the bloodstream.
Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.
An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.
Skin tests in which the sensitizer is applied to a patch of cotton cloth or gauze held in place for approximately 48-72 hours. It is used for the elicitation of a contact hypersensitivity reaction.
A chronic form of schizophrenia characterized primarily by the presence of persecutory or grandiose delusions, often associated with hallucination.
Psychiatry is the study of mental disorders and their diagnosis, management and prevention. Conditions include schizophrenia, severe depression and panic disorders among others. There are pharmaceutical treatments as well as other therapies to help...