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不能治疗与抑郁症相关的积极情绪下降的症状。针对与抗抑郁能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50 khz的快乐超声发声（hedonic USVs）是一种公认的积极情感状态的测量方法。使用这个模型，我们已经确定胰岛素样生长因子- 1在功能上参与了积极影响诱导的抗抑郁能力。在人类中，胰岛素样生长因子I （IGFI）已被证明既能增加积极影响，又能减轻抑郁和焦虑的症状，但外周副作用（低血糖）限制了其临床应用。本研究将进一步探讨IGFI抗抑郁能力的功能作用。在这些拟议的实验中，(i)将确定igfi诱导的积极影响和抗抑郁作用的最佳大脑区域，（ii）将使用多种动物积极影响和抑郁测量来检查igfi诱导的恢复能力，以及（iii）将确定胰岛素样生长因子结合蛋白2 （IGFBP-2）作为抑郁症治疗的治疗潜力。研究积极影响及其与抗抑郁能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.