Marijuana Use and Schizophrenia

描述(申请人提供)：这是一个项目的最后一次提交，该项目旨在调查精神分裂症患者和健康志愿者在大麻对大脑和行为影响方面的差异。总体目标是确定精神分裂症是否增加了对大麻使用的认知和临床影响的易感性。有流行病学证据表明，吸食大麻与精神分裂症的发病率较高有关。也有证据表明，大量使用大麻会导致急性精神病，也有证据表明，长期使用大麻会导致易感人群出现精神分裂症。此外，注射THC已被发现会导致健康志愿者中精神分裂症样症状的增加，并增加精神分裂症患者的症状。我们的研究团队在使用认知和临床指标以及复杂的大脑结构和功能测量来评估精神分裂症患者和正常志愿者之间的差异方面拥有丰富的专业知识。我们还在评估急性大麻使用对非精神分裂症大麻使用者的局部脑血流量(RCBF)和认知的影响方面也很有经验。这份R21申请提出了一项将这两个研究计划联系起来的研究。我们建议获取10名精神分裂症受试者和10名经常吸食大麻的正常志愿者的正电子发射计算机断层扫描和磁共振成像数据以及临床症状评分。在金钱奖励方案期间，将使用[150]水的PET成像来测量rCBF数据。受试者将接受一次含有[150]水的正电子发射计算机断层扫描，包括在吸安慰剂香烟之前和之后，以及在吸活性大麻香烟之前和之后。在PET成像期间，受试者将执行一项金钱奖励任务，这项任务在其他研究中被发现可以激活与奖励相关的大脑区域。PET图像将与高分辨率结构磁共振扫描共同配准进行分析。受试者还将在另一个场合接受神经心理测试。精神分裂症受试者的年龄、性别、父母的社会经济地位和吸烟史将与正常志愿者受试者相匹配。我们假设，吸食大麻对精神分裂症患者rCBF的影响将与我们在正常志愿者中看到的显著不同。更具体地说，我们假设精神分裂症受试者在基线(即吸食安慰剂后)的大脑奖赏系统中的rCBF将较低，但吸食大麻后将显示正常的奖赏激活模式。 与公共健康相关：越来越多的证据表明，大麻使用与精神分裂症之间存在联系，也有证据表明，精神分裂症患者的大脑奖励系统可能存在异常。这项研究将在一项奖励任务中使用PET成像来比较精神分裂症患者和健康志愿者的大脑血流变化，这些志愿者在吸食安慰剂或活性大麻香烟后经常使用大麻。这项研究的结果将进一步加深我们对精神分裂症潜在原因的理解，并可能为这种疾病的治疗提供新的可能性。

DESCRIPTION (provided by applicant): This is the final resubmission of a project designed to investigate differences between schizophrenic individuals and healthy volunteers in the effects of marijuana on the brain and behavior. The overall aim is to determine whether schizophrenia confers an increased liability to the cognitive and clinical effects of cannabis use. There is epidemiological evidence linking marijuana use with a higher incidence of schizophrenia. There is also evidence that acute psychosis can be induced by heavy marijuana use, as well as evidence that prolonged marijuana use can lead to the onset of schizophrenia in susceptible individuals. Additionally, injection of THC has been found to cause increased schizophrenia-like symptoms in healthy volunteers and to increase symptoms in patients with schizophrenia. Our research team has extensive expertise in assessing differences between schizophrenics and normal volunteers using cognitive and clinical indices, as well as sophisticated measures of brain structure and function. We are also experienced in assessing the effects of acute marijuana use on regional cerebral blood flow (rCBF) and cognition in non-schizophrenic users of marijuana. This R21 application proposes a study that links these two research programs. We propose acquiring PET and MR imaging data and clinical symptom ratings on 10 schizophrenic subjects and 10 matched normal volunteers who are regular users of marijuana. PET imaging with [15O]water will be used to measure rCBF data during a monetary reward protocol. Subjects will be scanned using PET with [15O]water on one occasion, before and after smoking a placebo cigarette, and before and after smoking an active marijuana cigarette. During PET imaging the subjects will perform a monetary reward task that was found to activate reward-related brain regions in other studies. The PET images will be co-registered to a high resolution structural MRI scan for analysis. The subjects will also be assessed on a separate occasion with a neuropsychological battery. The schizophrenic subjects will be matched by age, gender, parental SES, and smoking history to the normal volunteer subjects. We hypothesize that the effects of smoking marijuana on rCBF in schizophrenics will differ significantly from that seen in our normal volunteers. More specifically, we hypothesize that rCBF will be lower in brain reward systems in schizophrenic subjects at baseline (i.e., after smoking placebo), but will show a normal pattern of activation to reward after smoking marijuana. PUBLIC HEALTH RELEVANCE: There is increasing evidence that there is a link between marijuana use and schizophrenia, as well as evidence that schizophrenic individuals may have abnormalities in their brain reward systems. This study will use PET imaging during a reward task to compare blood flow changes in the brains of schizophrenics and healthy volunteers who regularly use marijuana after they smoke either a placebo or an active marijuana cigarette. Results of the study will further our understanding of the underlying causes of schizophrenia and could suggest new possibilities for treatment of this disorder.