Nicotine Effects on Endophenotypes of Schizophrenia
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 121
- 主要终点
- Error Percentage in Antisaccade Task
研究概览
简要总结
The purpose of this study is to test the effects of nicotine on cognition with the following schizophrenia endophenotypes: prepulse inhibition, antisaccades, the continuous performance test, spatial working memory and a verbal memory task. Schizophrenia patients, unaffected first-degree relatives of schizophrenia patients and healthy controls receive transdermal nicotine in a double-blind, placebo-controlled, crossover study.
详细描述
Convergent findings suggest that an altered neuronal nicotinic acetylcholine receptor system may contribute to the pathophysiology of schizophrenia. Nicotine consumption through cigarette smoking might represent a form of self-medication in schizophrenia as nicotine reduces cognitive and physiological deficits in schizophrenia. The present study aims to investigate how nicotine affects attentional and executive schizophrenia endophenotypes and how genetic polymorphisms relating to the cholinergic system might play a role in inter-individual differences in the magnitude of nicotine effects.
Schizophrenia patients, first-degree relatives of schizophrenia patients as well as healthy controls will receive transdermal nicotine in a double-blind, placebo-controlled, crossover study and will be assessed with prepulse inhibition, antisaccades, the continuous performance test, spatial working memory and a verbal memory task. Subjects will be overnight-abstinent smokers and non-smokers. However, the investigators will particularly test non-smokers in order to eliminate confounding effects of nicotine withdrawal and reinstatement.
Main hypotheses:
- Schizophrenia patients will perform worse than matched controls in all cognitive tests (validating our endophenotypes).
- Nicotine administration will enhance cognitive performance in overnight-abstinent smokers.
- Improvement of cognitive performance in smokers with schizophrenia will be stronger than in control smokers.
- Improvement of cognitive performance in smoking first-degree relatives of schizophrenia patients will be stronger than in control smokers.
- Nicotine administration will affect cognitive functioning in non-smoking subjects.
- Nicotine administration will improve cognitive functioning in non-smoking schizophrenia patients.
- The effects of nicotine in non-smoking subjects are stronger in those subjects who are cognitively more impaired (i.e. performing below the median of the respective group).
The present research contributes to the issue whether nicotinic cholinergic receptor agonists may have therapeutic value in the treatment of cognition in schizophrenia.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV) diagnosis of schizophrenia
- •age 18-55 years old
- •able to provide informed consent
- •treated with antipsychotic medications at a stable dose for at least 6 weeks
- •normal or corrected to normal vision
- •smokers (Fagerström Test for Nicotine Dependence > 4)
- •non-smokers (< 100 cigarettes/lifetime, not having smoked in the past year)
- •age 18-55 years old
- •able to provide informed consent
- •normal or corrected to normal vision
- •smokers (Fagerström Test for Nicotine Dependence > 4)
- •non-smokers (< 100 cigarettes/lifetime, not having smoked in the past year)
- •Unaffected First-Degree Relatives of Schizophrenia Patients:
- •same inclusion criteria as controls plus
- •having an adult first-degree relative (sibling, parent, child) with a DSM IV diagnosis of schizophrenia
排除标准
- •substance dependence
- •clinical instability
- •changes in medication in the last 6 weeks
- •anticholinergic medication
- •untreated hypertension
- •cardiovascular disease
- •insulin-dependent diabetes mellitus
- •phaeochromocytoma
- •uncontrolled hyperthyroidism
- •renal or hepatic impairment
- •central nervous system disease
- •pulmonary disease
- •generalised dermatological disorders (neurodermatitis, psoriasis, chronic dermatitis, urticaria, etc.)
- •gastric or intestinal ulcer
- •hypersensitivity to nicotine
- •allergy to patches
- •women: pregnancy, lactation
- •substance dependence
- •having a first-, second-, or third-degree relative with a psychotic disorder
- •DSM IV Axis I disorder
- •anticholinergic medication
- •untreated hypertension
- •cardiovascular disease
- •insulin-dependent diabetes mellitus
- •phaeochromocytoma
- •uncontrolled hyperthyroidism
- •renal or hepatic impairment
- •central nervous system disease
- •pulmonary disease
- •generalised dermatological disorders (neurodermatitis, psoriasis, chronic dermatitis, urticaria, etc.)
- •gastric or intestinal ulcer
- •hypersensitivity to nicotine
- •allergy to patches
- •women: pregnancy, lactation
- •Unaffected First-Degree Relatives of Schizophrenia Patients:
- •same exclusion criteria as controls
研究组 & 干预措施
Nicotine Patch
Transdermal nicotine patch
干预措施: Transdermal nicotine patch (Drug)
Placebo patch
Placebo patch
干预措施: Placebo patch (Drug)
结局指标
主要结局
Error Percentage in Antisaccade Task
时间窗: Three hours after patch application
Three hours after the application of a nicotine or a placebo patch, performance on the antisaccade task is assessed. In the antisaccade task participants visually fixate a central stimulus which is replaced by a sudden onset target that appears at some distance to the left or right. Participants are told to refrain from looking at the peripheral target, and direct their gaze instead in the opposite direction (i.e. they have to make an antisaccade). Participants typically fail to achieve this on a significant number of trials and instead make reflexive glances towards the target (i.e. making a so-called antisaccade error). Error percentage in the antisaccade task is the unit of measure in this task. Error percentage in the antisaccade task = number of antisaccade errors / total number of trials.
次要结局
未报告次要终点
研究者
Nadine Petrovsky
PhD
University Hospital, Bonn