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

 描述(申请人提供)：抑郁症和社交焦虑症是高度受损的疾病，通常是同时发生的，女性的发病率是男性的两倍。这些问题在较早出现焦虑症状的青少年中很常见，但往往在青春期出现或增加，特别是在女孩中。众所周知，抑郁与积极情绪/奖励反应的降低有关，而且越来越多的证据表明，患有社交焦虑的人也表现出减少的积极情绪。我们测试了一个模型，该模型提出，在青春期早期对社会威胁的敏感性会导致对环境中的社会回报的反应迟钝，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。大量研究表明，具有高恐惧气质或特质焦虑的青少年对威胁刺激，特别是传达潜在社会威胁的刺激，表现出更高的警觉性。女孩似乎对人际威胁特别敏感。在动物研究中，暴露在社会威胁下会导致多巴胺能变化和对奖励的迟钝反应。然而，人们对社会威胁如何影响青少年的奖赏功能知之甚少，特别是在青春期成熟期间，当社会威胁变得越来越突出时。我们认为，对社会威胁敏感的早期青春期女孩将在腹侧脑区(例如杏仁核、膝下扣带回皮质、内侧前额叶皮质、前脑岛和伏隔核)的情感显著网络中对社会威胁表现出更高的激活。这种反应性会导致一种行为倾向，即避免可能带来社会威胁的情况，即使这些情况也会带来潜在的回报(即结交新朋友，尝试一项新活动)。随着时间的推移，神经对社会威胁的反应性增加，以及与之相关的对可能的威胁情景的行为回避，可能会通过几个相互关联的机制改变奖励反应，包括：(A)纹状体对奖励的反应减少(B)社交接近动机减少，(C)对社会奖励线索的注意力减少，和/或(D)在社交互动中减少对积极情绪的主观体验。这些变化被认为在症状的出现和恶化中发挥了作用。我们在一项对早期青春期女孩的纵向研究中测试了这一模型，这些女孩在基线时被过度抽样，出现阈值以下的社交焦虑症状。这项研究将包括在模拟同伴互动任务中的神经成像，该任务探索对社会威胁和奖励的神经反应，行为和眼睛跟踪范式，日常社交的生态瞬时评估(EMA)，以及临床症状和青春期激素的同时评估。电池将在基线(T1；11-13岁)和两年后(T2；13-15岁)完成，并在T3(14-16岁)进行额外的临床评估。预计结果将突出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，这些因素可能会在敏感的发育窗口通过基于神经科学的干预而成为目标。

 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.