Marijuana and Mood: Frontal Predictors of Behavior

大麻和情绪：行为的额叶预测因素

• 批准号: 7305421
• 负责人: STACI A GRUBER
• 金额: $ 25.49万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7305421
• 关键词: Affective; Alcohol or Other Drugs use; Anisotropy; Anterior; Area; Behavior; Behavioral inhibition; Bipolar Disorder; Brain; Cannabinoids; Cannabis; Cannabis Smoking; Chronic; Cognitive; Complement; Data; Data Collection; Development; Device Designs; Devices; Diffusion Magnetic Resonance Imaging; Disease; Disinhibition; Electronics; Environment; Exhibits; Experimental Designs; Exposure to; Fiber; Frequencies; Functional Magnetic Resonance Imaging; Hand; Image; Imaging Techniques; Impairment; Impulsivity; Individual; Intervention; Investigation; Knowledge; Laboratories; Laboratory Finding; Link; Magnetic Resonance Imaging; Marijuana; Marijuana Dependence; Marijuana Smoking; Measures; Methods; Monitor; Moods; Neurobiology; Numbers; Patients; Pattern; Play; Population; Predictive Value; Rate; Relative (related person); Reporting; Risk; Risk Factors; Role; Scanning; Signal Transduction; Smoke; Smoker; Smoking; Substance Use Disorder; Substance abuse problem; Symptoms; System; Testing; Time; Week; Work; base; blood oxygen level dependent; cingulate cortex; design; disturbance in affect; frontal lobe; innovation; insight; mood regulation; neuroimaging; neuromechanism; non-smoking; novel; novel strategies; prospective; response; substance abuser; urinary; white matter; white matter change

DESCRIPTION (provided by applicant): This second revision of an R21 application is focused on a novel approach to the study of the neurobiology of marijuana use in subjects with and without bipolar disorder. The proposed investigation is designed to examine the extent to which structural changes in the frontal cortex and the functional response of the anterior cingulate are associated with poor inhibitory function and mood fluctuation in subjects with chronic heavy cannabis use and cannabis users with bipolar disorder. In addition, we will examine whether these frontal changes are predictive of behavior. Several studies have shown that bipolar patients have extremely high rates of comorbid substance use, and that cannabis is often used to alleviate severe mood symptoms. In recent work from our laboratory, we have found alterations in diffusion tensor imaging (DTI) measures of frontal white matter as well as BOLD changes in anterior cingulate (AC) and dorsolateral prefrontal activity (DLPFC) during the completion of an inhibitory challenge paradigm in chronic heavy marijuana (MJ) smokers. We have also reported alterations in functional activity in this region in patients with bipolar disorder. These findings complement previous reports and suggest that this region may play a crucial role in the modulation of inhibitory functions in both disorders. To date, no investigation has examined these neurobiologic correlates with regard to their potential predictive value regarding mood changes and number of episodes of smoking. We will apply DTI and blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) techniques to measure differences in white matter and regional activation in focal brain areas during cognitive and affective challenge paradigms in 20 chronic, heavy MJ smokers, 20 chronic heavy MJ smokers with Bipolar I disorder, 20 Bipolar patients who do not smoke MJ, and 20 healthy non-smoking control subjects. We also propose to examine "real time" mood changes and cannabis use with handheld electronic devices designed for use within subjects' own environments. This data will be used to test the hypotheses that: 1) BOLD signal changes will be different in MJ smokers with and without bipolar disorder relative to control subjects; 2) DTI measure of white matter will be altered in MJ smokers with and without bipolar disorder; and 3) fMRI BOLD and DTI measures will predict changes in mood, measures of impulsivity and frequency of smoking in a four week period following the scanning session. To our knowledge, no studies have utilized neuroimaging measures as predictors of behavior. Data on behavior and ratings of mood will be collected in "real time" within subjects' own environment, using a handheld PDA device. This investigation is innovative, in that it includes data acquired from fMRI and DTI techniques as predictors of real time behavior in substance abusers. We believe these findings may help identify potential risk factors for substance use disorders, as well as guide the development of new treatment interventions. The proposed investigation is designed to examine the extent to which structural changes in the frontal cortex and the functional response of the anterior cingulate cortex are associated with poor inhibitory function and mood fluctuation in subjects with chronic heavy cannabis use with and without bipolar disorder. In addition, we will examine whether frontal changes are predictive of mood alterations and frequency of smoking using "real time" assessments of mood and behavior. The unique, previously untapped combination of structural, functional, and diffusion tensor imaging methods applied to these populations allows for rigorous examination of specific cortical regions involved in cannabis dependence, allowing for the identification of potential risk factors for substance abuse and may provide important information regarding the development of new treatment interventions.

描述（由申请人提供）：R21申请的第二次修订集中在研究大麻在双相情感障碍和非双相情感障碍受试者中使用的神经生物学的新方法。拟议的调查旨在检查额叶皮层的结构变化和前扣带的功能反应在多大程度上与慢性重度大麻使用者和双相情感障碍的大麻使用者的抑制功能差和情绪波动有关。此外，我们将研究这些额叶变化是否可以预测行为。几项研究表明，双相情感障碍患者的共病药物使用率极高，大麻经常被用来缓解严重的情绪症状。在我们实验室最近的工作中，我们发现慢性重度大麻（MJ）吸烟者在完成抑制挑战范式时，额叶白质的扩散张量成像（DTI）测量以及前扣带（AC）和背外侧前额叶活动（DLPFC）的BOLD变化。我们也报道了双相情感障碍患者该区域功能活动的改变。这些发现补充了先前的报道，并表明该区域可能在两种疾病的抑制功能调节中起关键作用。到目前为止，还没有研究检验这些神经生物学相关性对情绪变化和吸烟次数的潜在预测价值。我们将应用DTI和血氧水平依赖（BOLD）功能磁共振成像（fMRI）技术测量20名慢性重度MJ吸烟者、20名慢性重度MJ吸烟者合并双相I型障碍、20名不吸烟MJ的双相患者和20名健康非吸烟对照者在认知和情感挑战范式期间脑局灶区白质和区域激活的差异。我们还建议使用手持电子设备来检测“实时”情绪变化和大麻使用情况，这些设备是为受试者在自己的环境中使用而设计的。这些数据将用于验证以下假设：1)与对照组相比，患有和不患有双相情感障碍的MJ吸烟者的BOLD信号变化将有所不同；2) MJ吸烟者伴或不伴双相情感障碍的白质DTI测量会发生改变；3) fMRI BOLD和DTI测量将预测扫描后四周内情绪、冲动和吸烟频率的变化。据我们所知，还没有研究利用神经成像测量作为行为的预测指标。有关行为和情绪评级的数据将在受试者自己的环境中“实时”收集，使用手持PDA设备。这项研究是创新的，因为它包括从功能磁共振成像和DTI技术获得的数据，作为药物滥用者实时行为的预测指标。我们相信这些发现可能有助于确定物质使用障碍的潜在风险因素，并指导新的治疗干预措施的发展。拟议的调查旨在检查额叶皮层的结构变化和前扣带皮层的功能反应在多大程度上与慢性重度大麻使用伴或不伴双相情感障碍的受试者的抑制功能差和情绪波动有关。此外，我们将通过对情绪和行为的“实时”评估来检验额叶变化是否能预测情绪变化和吸烟频率。将结构、功能和扩散张量成像方法的独特组合应用于这些人群，可以对涉及大麻依赖的特定皮质区域进行严格检查，从而确定药物滥用的潜在风险因素，并可能为开发新的治疗干预措施提供重要信息。