IGFI and Depression

IGFI 与抑郁症

基本信息

批准号：
8609073
负责人：
Jeffrey Scott Burgdorf
金额：
$ 38.86万
依托单位：
NORTHWESTERN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-04-06 至 2017-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8609073
关键词：
Acute Adult Adverse effects Affect Affective Animal Model Animals Antidepressive Agents Anxiety Behavior Binding Binding Proteins Brain Brain region Cause of Death Chronic Chronic stress Clinical Dependence Depressed mood Development Dorsal Dose Eating Emotions Future Goals Human Hypoglycemia Infusion procedures Injection of therapeutic agent Insulin-Like Growth Factor I Insulin-Like Growth-Factor-Binding Proteins Laboratory Animals Lateral Lead Measures Medial Mental Depression Microinjections Modeling Molecular Oral Pathway interactions Patients Peripheral Play Population Positioning Attribute Property Proteins Rattus Reaction Recombinant Insulin-Like Growth Factor Regimen Role Signal Transduction Small Interfering RNA Stress Sucrose Symptoms Taste Perception Testing Therapeutic Time Tongue Ultrasonics Work alternative treatment depressive symptoms global health hedonic human IGFBP2 protein inhibitor/antagonist insight loss of function mortality novel novel therapeutics research study resilience response small molecule stressor therapeutic development therapeutic target vocalization

项目摘要

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.

描述（由申请人提供）：在人类中，积极的情感状态与抑郁症的韧性以及增加的全球健康和死亡率降低有关。目前可用的抗抑郁药无法治疗与抑郁症相关的阳性影响降低的症状。靶向与抑郁症的弹性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Hedonic 50-KHz超声波声（Hedonic USV）是对积极情感状态的良好衡量。使用该模型，我们已经确定了胰岛素样生长因子I在功能上与阳性诱导的抑郁症的韧性有关。在人类中，已经证明胰岛素样生长因子I（IGFI）既增加积极影响并减轻抑郁症和焦虑症状，但是外周副作用（低血糖）限制了其临床实用性。拟议的研究将研究IGFI韧性对抑郁症的功能作用。在这些提出的实验中，（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）IGFI诱导的弹性将使用阳性和抑郁的多种动物度量进行检查，（iii）胰岛素样生长因子的治疗潜力（III）将确定抑郁症的胰岛素样生长因子的治疗潜力。研究积极的影响及其与抑郁症的韧性如何相关，是一种独特的方法，可能导致新型抗抑郁药的产生。