Sex Differences in the Affective Response to Repeated Negative Stimuli

对重复负面刺激的情感反应的性别差异

• 批准号: 8443130
• 负责人: Lisa Feldman Barrett
• 金额: $ 21.75万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-12-01 至 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8443130
• 关键词: Address; Affect; Affective; Affective Symptoms; Amygdaloid structure; Anterior; Anxiety; Brain; Brain region; Clinical; Data; Disease; Emotions; Endocrine disruption; Endogenous depression; Equipment and supply inventories; Exhibits; Extinction (Psychology); Film; Fright; Functional Magnetic Resonance Imaging; Functional disorder; Future; Generalized Anxiety Disorder; High Risk Woman; Hormonal; Hydrocortisone; Image; Individual; Insula of Reil; Laboratories; Lead; Major Depressive Disorder; Measures; Mental Depression; Mood Disorders; Neurobiology; Participant; Pathology; Patient Self-Report; Pattern; Phase; Population; Predisposition; Prevention; Process; Relative (related person); Research; Research Project Grants; Resistance; Risk; Salivary; Sampling; Scanning; Sex Characteristics; Stimulus; Surveys; Symptoms; System; Temperament; Testing; Trauma; Woman; base; dysphoria; effective therapy; experience; interest; memory process; men; neuroimaging; novel; post-traumatic stress; public health relevance; regional difference; relating to nervous system; research study; response; sex; trait

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.

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，因此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尚不清楚。 有人认为，由于情感处理方面存在更普遍的性别差异，女性患这些疾病的风险更高。多项神经影像学研究支持了这一观点，显示男性和女性对情感材料的反应程度存在区域差异。然而，这些研究并未得出一致的性别差异模式，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揭示了情感处理中的一种新的性别差异，这种差异不在于情感反应的强度，而在于这种反应在多次重复中的持续性。我们的数据表明，虽然当这些项目是新奇的时，情感回路对负价刺激的反应在性别之间没有差异，但女性对通过重复呈现而熟悉的消极项目的反应明显大于男性。这表明女性情感系统对负面刺激的适应速度明显慢于男性。 对高度焦虑的人的研究表明，与健康对照组相比，在恐惧消失期间，情感网络的活动也同样持续。因此，女性情感反应的持续存在可能解释了她们更容易患情感障碍。在本提案中，我们将测试这种可能性。使用功能磁共振成像，我们将首先全面描述女性和男性不同情感感兴趣区域对情绪诱发材料的反应的习惯曲线，从而确认性别差异。然后将这些数据与各种情感干扰测量进行比较，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沉思。 我们预测，相对于男性，女性在杏仁核、岛叶和前扣带回等区域将表现出更持久的反应，并且在多次重复后这些反应的强度将与情感功能障碍的测量相关，例如那些情感功能最持久的人反应也将显示出最多的症状。我们进一步预测，当一周后看到熟悉的情感材料时，女性在情感网络中的反应将比男性更大。如果这些预测得到证实，则表明对负面刺激的习惯率可以预测情感障碍的症状。因此，由于习惯速度较慢在女性中更为常见，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中性别差异的潜在因素可能会导致更加个性化和有效的治疗。