The role of endogenous oxytocin in adult psychosocial adjustment: main effects and interactions with serotonergic and dopaminergic modulators of social cognition

 描述(申请人提供)：催产素是一种神经内分泌肽，最初因其在交配和繁殖中的作用而闻名，最近因其对社会认知的广泛影响而在科学和非科学受众中流行。催产素通常被吹捧为“爱的荷尔蒙”，它影响我们如何处理、处理和回应与情感和社会相关的刺激，这反过来又影响我们如何与他人合作、信任和沟通。因此，临床医生开始对患有某些精神障碍的患者使用药物催产素也就不足为奇了，这些患者包括自闭症、精神分裂症和抑郁症，目的是改善他们的情绪健康和社会关系质量。然而，外源性催产素对这些个体显示出治疗效果的事实可能会给人一种错误的印象，即催产素对普通人群普遍有益。事实上，有新的文献表明，催产素的应用会恶化健康成年人的心理社会适应，这导致了人们的猜测，即高水平的催产素会促进已经在情绪上协调的人的不适应超敏反应。这种不同的结果可能反映了内源性催产素系统中预先存在的个体间的差异，和/或存在调节催产素行为影响的类似特征的背景因素。然而，我们对自然产生的催产素水平的心理社会相关性知之甚少，也不知道这种水平如何在成年期或作为性别的函数而波动。同样，我们对其他神经递质系统(如多巴胺和5-羟色胺)的影响程度和性质知之甚少，这些神经递质系统与催产素相互作用，并对社会认知产生自己的影响。为了解决这些关键的知识差距，本研究将在一个健康的社区样本(N=240，年龄20-80岁)中使用外周生物标记物分析、神经心理评估和行为测试来实现四个主要目标：(1)表征与内源性催产素水平相关的临床相关的心理社会适应模式；(2)绘制成年阶段催产素依赖的心理社会适应变化的发展轨迹；(3)测试特定认知和情感特征对催产素介导的社会认知过程的调节影响，以及(4)验证二维液相色谱-串联质谱仪作为测定人唾液中催产素水平的超灵敏技术。这一新的知识将有助于我们理解催产素如何影响心理社会痛苦的恢复能力，并提供急需的生物标记物标准来帮助从业者优化催产素的操作。

 DESCRIPTION (provided by applicant): Oxytocin is a neuroendocrine peptide originally known for its role in mating and reproduction and more recently popularized among scientific and lay audiences for its seemingly broad-reaching effects on social cognition. Often touted as the "love hormone", oxytocin influences how we attend to, process, and respond to emotionally- and socially-relevant stimuli, which, in turn, affects how we cooperate, trust, and communicate with others. It is therefore not surprising that clinicians have begun administering pharmaceutical oxytocin to patients with certain psychiatric disturbances, including autism, schizophrenia, and depression, with the goal to improve their emotional well-being and quality of social relationships. The fact that exogenous oxytocin shows therapeutic effects for such individuals may, however, give a false impression that oxytocin is universally beneficial for the general population. Indeed, there is an emerging literature to suggest that oxytocin administration can worsen psychosocial adjustment in healthy adults, which has led to the speculation that high oxytocin levels promote a maladaptive hypersensitivity in individuals who are already emotionally attuned. Such differential outcomes may reflect pre-existing, inter-individual differences in the endogenous oxytocin system and/or presence of trait-like contextual factors that moderate the behavioral effects of oxytocin. However, we know little about the psychosocial correlates of naturally-occurring oxytocin levels or how such levels might fluctuate across adulthood or as a function of sex. Similarly, we know little about the degree and nature of influence of other neurotransmitter systems (e.g., dopamine and serotonin) that interact with oxytocin and exert their own effects on social cognition. To address these critical gaps in knowledge, this research will use peripheral biomarker assay, neuropsychological assessment, and behavioral testing in a healthy community sample (N = 240, ages 20-80) to achieve four principle goals: (1) to characterize clinically-relevant patterns of psychosocial adjustment associated with endogenous oxytocin levels, (2) to map the developmental trajectory of oxytocin-dependent changes in psychosocial adjustment across stages of adulthood, (3) to test the moderating influence of specific cognitive and affective traits on oxytocin-mediated social cognitive processes, and (4) to validate 2-D liquid chromatography-tandem mass spectrometry as an ultra-sensitive technique for quantifying oxytocin level in human saliva. This new knowledge will aid our understanding of how oxytocin influences resilience toward psychosocial distress and provide much needed biomarker norms to assist practitioners in the optimization of oxytocin manipulation.