fMRI of Craving in Addictions: Gender Differences

描述（由申请人提供）：我们旨在研究行为和药物成瘾的性别差异，以改进预防和治疗策略。冲动或渴望在行为和药物成瘾中是常见的，通常在参与成瘾行为之前，因此是干预的重要目标。因此，对渴望状态背后的大脑机制的进一步了解具有重要的临床意义。我们已经建立，测试并发表了fMRI范式，研究可卡因依赖（CD）中的可卡因渴望和病理性赌博（PG）中的赌博冲动的神经相关性。然而，这些研究主要或只涉及男性，造成了我们对女性渴望的理解不足。我们建议将研究范围扩大到妇女。我们假设患有PG的女性和男性的赌博冲动以及患有CD的女性和男性的可卡因渴望的大脑机制存在差异。具体来说，我们使用fMRI发现PG男性在诱导赌博冲动和执行冲动控制任务时腹前扣带（vAC）的活动相对减少。根据我们的初步数据，我们假设，当看到赌博线索时，与患有PG的男性相比，女性的vAC活动减少得更多，这一区域与冲动控制和情绪调节的多项研究有关。在以男性为主的乳糜泄组对可卡因渴望的功能磁共振成像研究中，我们（和其他人）观察到乳糜泄组在观察可卡因线索时大脑边缘（AC）的激活。初步研究发现，与患有乳糜泻的男性相比，女性对可卡因的渴望在杏仁核的边缘激活方面存在差异，这为有关动机和情绪状态中与性相关的杏仁核激活差异的新兴文献增加了新的内容。我们假设患有乳糜泻的女性和男性在看到可卡因线索时在AC和杏仁核激活方面会表现出差异。我们将使用我们建立的fMRI范式和改进的方法，包括更高分辨率成像和并发心率监测，来研究这些假设。鉴于我们正在进行的将fMRI范式纳入治疗试验的工作，拟议调查的结果不仅应该提高对PG， CD生物学和成瘾中的性别差异的一般理解，而且还有助于指导性别知情的预防和治疗工作。

DESCRIPTION (provided by applicant): We aim to study gender-related differences in behavioral and drug addictions in order to improve prevention and treatment strategies. Urges or cravings are common to behavioral and drug addictions, generally precede participation in the addictive behavior, and thus represent important targets for interventions. An improved understanding of brain mechanisms underlying craving states thus has significant clinical implications. We have established, tested and published on fMRI paradigms investigating the neural correlates of cocaine cravings in cocaine dependence (CD) and gambling urges in pathological gambling (PG). However, these studies have involved predominantly or exclusively men, creating a deficiency in our understanding of craving in women. We propose extending our studies to involve women. We hypothesize that there will exist differences in the brain mechanisms underlying gambling urges in women and men with PG and cocaine cravings in women and men with CD. Specifically, we used fMRI and found relatively decreased activity in the ventral anterior cingulate (vAC) in men with PG during the induction of gambling urges and while performing an impulse control task. Based on our preliminary data, we hypothesize that when viewing gambling cues, women as compared to men with PG experience a greater decrease in vAC activity, a region implicated in multiple studies of impulse control and mood regulation. In our fMRI study of cocaine craving in a predominantly male CD group, we (and others) observed limbic activation (in AC) in the CD group viewing cocaine cues. Preliminary studies investigating cocaine cravings in women as compared to men with CD have found differences in limbic activations in the amygdala, adding to an emerging literature on sex-related amygdala activation differences in motivational and emotional states. We hypothesize that women and men with CD will show differences in AC and amygdala activation during viewing of cocaine cues. We will use our established fMRI paradigm and improved methodologies, including higher resolution imaging and concurrent heart rate monitoring, to investigate these hypotheses. Given our ongoing work to incorporate this fMRI paradigm into treatment trials, the results from the proposed investigation should not only improve the general understanding of the biologies of PG, CD and gender differences in addictions, but also help guide gender-informed prevention and treatment efforts.