Influence of Social Threat on Reward Function in At-Risk Adolescent Girls - Supplement

 描述（由申请人提供）：抑郁症和社交焦虑症是高度损害性的疾病，通常同时发生，女性的发病率是男性的两倍。这些问题在青少年中很常见，早期有焦虑症状，但往往在青春期出现或增加，特别是在女孩中。众所周知，抑郁症与积极影响/奖励反应能力的降低有关，越来越多的证据表明，社交焦虑的个体也表现出积极影响的降低。我们测试了一个模型，提出在青春期早期对社会威胁的敏感性会导致对环境中社会奖励的反应迟钝，这反过来又会导致青春期后期社交焦虑和抑郁症状的增加。大量的研究表明，具有高水平恐惧气质或特质焦虑的青少年对威胁性刺激，特别是对潜在的社会威胁性刺激表现出更高的警惕性。女孩似乎对人际威胁特别敏感。在动物研究中，暴露于社会威胁会导致多巴胺能变化和对奖励的反应迟钝。然而，很少有人知道社会威胁如何有助于奖励功能在人类青少年，特别是在青春期成熟的时期，当社会威胁变得越来越突出。我们认为，对社会威胁敏感的早期青春期女孩将在参与个人显著威胁的腹侧脑区的情感显着网络中表现出对社会威胁的激活增加（例如杏仁核，膝下前扣带皮层，内侧前额叶皮层，前扣带皮层和丘脑核）。这种反应将有助于行为倾向，以避免潜在的社会威胁的情况下，即使这些情况也带来潜在的fr奖励（即结交新朋友，尝试新活动）。随着时间的推移，对社会威胁的神经反应性增加以及对可能的威胁场景的相关行为回避可以通过几种相互关联的机制改变奖励反应性，包括：（a）减少纹状体对奖励的反应（B）减少社会接近动机，（c）减少对社会奖励线索的注意力，和/或（d）减少社会互动期间积极情绪的主观体验。这些变化被认为在症状的出现和加重中发挥作用。我们测试这个模型在一个纵向研究的早期青春期女孩过采样的阈下症状的社交焦虑在基线。该研究将包括在模拟同伴互动任务期间的神经成像，其探测对社会威胁和奖励的神经反应、行为和眼动跟踪范例、以及日常社会互动的生态瞬时评估（EMA），沿着临床症状和青春期激素的同时评估。将在基线（T1; 11-13岁）和2年后（T2; 13-15岁）完成组合测试，并在T3（14-16岁）进行额外的临床评估。预计结果将强调女孩社交焦虑和抑郁的潜在可改变的共同神经行为风险因素，这些风险因素可以在敏感的发育窗口期通过基于神经科学的干预措施来针对。

 DESCRIPTION (provided by applicant): Depression and social anxiety are highly impairing disorders that often co-occur and are twice as frequent in women compared to men. These problems are common in adolescents with earlier symptoms of anxiety, but tend to emerge or increase during adolescence, especially in girls. Depression is known to be associated with reduced positive affect/reward responsiveness, and growing evidence indicates that individuals with social anxiety also show reduced positive affect. We test a model proposing that sensitivity to social threat during early adolescence leads to blunted responsiveness to social rewards in the environment, which in turn contributes to increases in social anxiety and depressive symptoms later in adolescence. A large body of research shows that youth with high levels of fearful temperament or trait anxiety display increased vigilance for threatening stimuli, especiall stimuli conveying potential social threat. Girls appear to be particularly sensitive to interpersonl threats. In animal studies, exposure to social threats leads to dopaminergic changes and blunted responsiveness to reward. Yet, little is known about how social threats contribute to reward functioning in human adolescents, particularly during the period surrounding pubertal maturation, when social threats become increasingly salient. We propose that early adolescent girls who are sensitive to social threat will exhibit increased activation to social threat in an affective salience network of ventral brain regions involved in attending to personally salient threats (e.g. amygdala, subgenual anterior cingulate cortex, medial prefrontal cortex, anterior insula, and nucleus accumbens). This reactivity will contribute to a behavioral tendency to avoid situations that carry potential for social threat even when these situations also carry potential fr reward (i.e. making new friends, trying a new activity). Over time, increased neural reactivity to social threats and associated behavioral avoidance of possible threatening scenarios could alter reward responsiveness through several inter- related mechanisms, including: (a) reduced striatal response to reward (b) reduced social approach motivation, (c) reduced attention toward social reward cues, and/or (d) reduced subjective experience of positive emotion during social interactions. These changes are proposed to play a role in the emergence and exacerbation of symptoms. We test this model in a longitudinal study of early adolescent girls oversampled for subthreshold symptoms of social anxiety at baseline. The study will include neuroimaging during simulated peer interaction tasks that probe neural response to social threat and reward, behavioral and eye tracking paradigms, and Eco- logical Momentary Assessment (EMA) of daily social interactions, along with concurrent assessment of clinical symptoms and pubertal hormones. The battery will be completed at baseline (T1; ages 11-13) and 2 years later (T2; ages 13-15), with an additional clinical assessment at T3 (ages 14-16). Results are expected to high- light potentially modifiable shared neurobehavioral risk factors for social anxiety and depression in girls that could be targeted through neuroscience-based interventions during a sensitive developmental window.