fMRI of Craving in Addictions: Gender Differences

描述(由申请者提供)：我们的目标是研究行为和药物成瘾的性别差异，以改进预防和治疗策略。冲动或渴望是行为和药物成瘾的共同之处，通常先于参与成瘾行为，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更好理解具有重要的临床意义。我们已经建立、测试并在功能磁共振成像上发表了研究可卡因依赖(CD)中的可卡因渴求和病理性赌博(PG)中的赌博冲动的神经相关性的范式。然而，这些研究主要或完全涉及男性，造成了我们对女性渴望的理解的不足。我们建议将我们的研究范围扩大到妇女。我们假设，女性和男性PG患者和男性患者的赌博冲动背后的大脑机制存在差异，CD患者的女性和男性患者对可卡因的渴望也不同。具体地说，我们使用功能磁共振成像发现，在PG患者诱导赌博冲动和执行冲动控制任务期间，腹侧前扣带回(VAc)的活动相对减少。根据我们的初步数据，我们假设，当观看赌博线索时，与患有PG的男性相比，女性经历了更大的vac活动下降，这一区域与多项关于冲动控制和情绪调节的研究有关。在我们对以男性为主的CD组的可卡因渴求的fMRI研究中，我们(和其他人)在观看可卡因线索的CD组中观察到边缘激活(AC)。对女性和患有CD的男性的可卡因渴求进行的初步研究发现，杏仁核边缘的激活存在差异，这是一篇关于性行为相关的杏仁核在动机和情绪状态下的激活差异的新文献。我们假设，在观看可卡因线索的过程中，患有CD的女性和男性在AC和杏仁核激活方面会表现出不同。我们将使用我们已建立的功能磁共振成像范例和改进的方法，包括更高分辨率的成像和同步心率监测，来研究这些假说。鉴于我们正在进行的将功能磁共振成像范式纳入治疗试验的工作，拟议的调查结果不仅应该提高对PG、CD的生物学和成瘾中的性别差异的总体理解，而且还有助于指导了解性别信息的预防和治疗工作。

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.