Sex Differences in the Affective Response to Repeated Negative Stimuli

描述（由申请人提供）：众所周知，情感障碍的发生率表现出明显的性别差异，例如，与男性相比，女性对抑郁症和创伤后应激障碍等疾病的易感性是男性的两倍。然而，目前，这种差异的神经基础还没有得到很好的理解。 有人认为，女性患这些疾病的风险更高，这是因为在情感处理方面存在更普遍的性别差异。多项神经影像学研究支持了这一观点，显示出男性和女性对情感材料的反应程度存在区域差异。然而，这些研究并没有集中在一致的性别差异模式上，也没有将神经性别差异与病理症状联系起来。 我们实验室的初步证据显示，在情感处理方面存在一种新的性别差异，这种差异并不存在于情感反应的大小上，而是存在于这种反应在多次重复中的持续性上。我们的数据表明，虽然负效价刺激的情感回路的反应并没有性别之间的差异时，这些项目是新的，负项目，已熟悉通过重复演示的反应是显着的女性比男性。这表明，女性的情感系统对负面刺激的适应速度明显慢于男性。 对高度焦虑的个体的研究表明，相对于健康对照组，在恐惧消退期间，情感网络中的活动也同样持续。因此，女性情感反应的持续性可能解释了她们对情感障碍的更大易感性。在本提案中，我们将测试这种可能性。使用功能磁共振成像，我们将首先充分表征在女性和男性的各种感兴趣的情感区域的情绪诱导材料的反应的习惯化曲线，确认性别差异。然后将这些数据与情感破坏的各种测量进行比较，包括测量抑郁和焦虑的多个清单，HPA轴反应性测试和自我报告的反刍。 我们预测，女性将在杏仁核，杏仁核和前扣带回等区域表现出相对于男性更持久的反应，并且在多次重复之后这些反应的大小将与情感功能障碍的测量相关，因此那些具有最持久情感反应的人也将表现出最多的症状。我们进一步预测，女性将有更大的反应，在情感网络比男性时，熟悉的情感材料可视化一周后。如果这些预测得到证实，这将表明对负面刺激的习惯化速度预测了情感障碍的症状。因此，由于女性习惯化的速度较慢，她们作为一个群体更容易受到情感障碍的影响。更好地了解情感障碍性别差异的潜在因素可能会导致更个性化和更有效的治疗。

DESCRIPTION (provided by applicant): It is well-established that the rate of disorders of affect exhibits a pronounced sex difference, such that susceptibility to disorders such as depression and post-traumatic stress is twice as high in women when compared to men. At present, however, the neural basis of this difference is not well understood. It has been suggested that women are at higher risk for these disorders due to a more general sex difference in the processing of affect. Multiple neuroimaging studies have supported this view, showing regional differences between men and women in the magnitude of the response to affective material. However, these studies have not converged on a consistent pattern of sex differences, nor have they related neural sex differences to pathological symptoms. Preliminary evidence from our lab has revealed a novel sex difference in affective processing, found not in the magnitude of the affective response, but rather in the persistence of that response over multiple repetitions. Our data indicate that while the response of the affective circuitry to negatively valenced stimuli does not differ between the sexes when those items are novel, the response to negative items that have been familiarized through repeated presentation is significantly greater in women than it is in men. This suggests that the affective systems of women habituate significantly more slowly to negative stimuli than do men's. Studies of individuals with high anxiety have shown similarly sustained activity in the affective network during the extinction of fear relative to healthy controls. Thus, it may be the case that the persistence of the affective response in women explains their greater susceptibility to affective disorder. In this proposal, we will test that possibility. Using fMRI, we will first fully characteize the habituation curves for the response to emotion-inducing material in various affective regions of interest in women and men, confirming the sex difference. These data will then be compared to various measures of affective disruption, including multiple inventories measuring depression and anxiety, tests of HPA axis responsiveness, and self-reported rumination. We predict that women will show longer-lasting responses in regions including amygdala, insula, and anterior cingulate relative to men, and that the magnitude of these responses after numerous repetitions will correlate with measures of affective dysfunction, such that those with the most persistent affective responses will also show the most symptoms. We further predict that women will have greater responses in the affective network than men when familiar affective material is visualized one week later. If these predictions are confirmed, it would indicate that the rate of habituation to negative stimuli predicts symptoms of affective disorder. Thus, as a slower rate of habituation is more common in women, they are more susceptible to disorders of affect as a group. A better understanding of the factors underlying sex differences in affective disorder could lead to more personalized and effective treatment.