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: 8589013
• 负责人: Lisa Feldman Barrett
• 金额: $ 26.1万
• 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/8589013
• 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）：良好的表明，情感疾病的性别差异表现出明显的性别差异，因此与男性相比，女性对抑郁症和创伤后压力等疾病的敏感性是女性的两倍。然而，目前，这种差异的神经基础尚不清楚。 有人提出，由于情感处理中的性别差异更大，因此妇女患这些疾病的风险更高。多次神经影像学研究支持了这一观点，显示了男女对情感物质的反应的区域差异。但是，这些研究尚未融合性别差异的一致模式，也没有将神经性别差异与病理症状相关。 我们实验室的初步证据揭示了情感处理中的新型性别差异，不是在情感反应的范围内，而是在多次重复的情况下这种反应的持久性。我们的数据表明，尽管情感电路对否定价值刺激的响应在这些项目是新颖时之间的性别之间没有差异，但女性对通过重复介绍所熟悉的负面项目的反应比男性中的男性要大得多。这表明，女性的情感系统比男性的习惯更慢于负面刺激。 在恐惧相对于健康对照组的灭绝期间，对焦虑症患者的研究表明，在情感网络中的持续活动类似。因此，可能是女性情感反应的持久性解释了她们对情感障碍的敏感性。在此提案中，我们将测试这种可能性。使用fMRI，我们将首先充分召集习惯曲线，以响应男女感兴趣的各种情感区域对情绪引起情绪的材料的反应，从而确认性别差异。然后，将将这些数据与情感中断的各种措施进行比较，包括测量抑郁和焦虑的多个库存，HPA轴响应能力的测试以及自我报告的反省。 我们预测，女性将在包括杏仁核，岛状和与男性的前扣带回等区域中显示出更长的反应，并且在许多重复次数后，这些反应的大小将与情感功能障碍的度量相关，以至于那些具有最持久的情感反应的措施也会显示出最大的症状。我们进一步预测，在一周后可视化熟悉的情感材料时，女性在情感网络中的反应将比男性更大。如果确认这些预测，则表明习惯率对负刺激的速度可以预测情感障碍的症状。因此，作为习惯较慢的习惯率在女性中更为普遍，她们更容易受到一组情感障碍的影响。更好地了解情感障碍中性别差异的因素可能会导致更具个性化和有效的治疗。