IGFI and Depression

描述（由申请人提供）：在人类中，积极的情感状态与抗抑郁能力以及全球健康水平的提高和死亡率的降低有关。目前可用的抗抑郁药未能治疗与抑郁症相关的积极情感减少的症状。针对与抑郁恢复力相关的积极情感状态是一种有吸引力的替代治疗方法。大鼠享乐50 kHz超声发声（享乐USVs）是一个良好的建立措施，积极的情感状态。使用这个模型，我们已经确定胰岛素样生长因子-I在功能上参与积极情绪诱导的抑郁恢复力。在人类中，胰岛素样生长因子I（IGFI）已被证明可以增加积极的影响并减少抑郁和焦虑的症状，但外周副作用（低血糖）限制了其临床用途。本研究将进一步探讨IGFI抗抑郁能力的功能作用。在这些提出的实验中，（i）将确定IGFI诱导的积极情感和抗抑郁作用的最佳脑区域，（ii）将使用积极情感和抑郁的多动物测量来检查IGFI诱导的恢复力，以及（iii）将确定胰岛素样生长因子结合蛋白2（IGFBP-2）作为抑郁治疗的治疗潜力。研究积极影响以及它与抑郁症恢复力的关系是一种独特的方法，可能会导致新型抗抑郁药的产生。

DESCRIPTION (provided by applicant): In humans, positive affective states are associated with resilience to depression as well as increased global health and decreased mortality. Currently available antidepressants fail to treat the symptom of decreased positive affect associated with depression. Targeting positive affective states associated with resilience to depression is an attractive alternative treatment approach. Rat hedonic 50-kHz ultrasonic vocalizations (hedonic USVs) are a well established measure of positive affective states. Using this model, we have identified Insulin-like Growth Factor-I as functionally involved in positive- affect-induced resilience to depression. In humans, Insulin-like Growth Factor I (IGFI) has been shown to both increase positive affect and reduce symptoms of depression and anxiety, but peripheral side effects (hypoglycemia) limits its clinical utility. The proposed studies will furthr examine the functional role of IGFI resilience to depression. In these proposed experiments, (i) the optimal brain region for IGFI-induced positive affect and antidepressant effects will be determined, (ii) IGFI-induced resilience will be examined using multiple animal measure of positive affect and depression, and (iii) the therapeutic potential of Insulin-like growth factor binding protein 2 (IGFBP-2) as a treatment for depression will be determined. Studying positive affect and how it relates to resilience to depression is a unique approach that may lead to the creation of novel antidepressants.