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.

Public Health Relevance

Depression affects over 10% of the adult population and is projected to become the second leading cause of death by 2020. Less than 30% of depressed patients respond to currently available antidepressants which work primarily by decreasing negative emotions. In this application, the mechanism of IGFI-induced positive affect and resilience to depression will be studied with the goal of providing mechanistic insight, as well as creating a novel therapeutic development pathway, for the treatment of depression.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH094835-02
Application #
8456082
Study Section
Neurobiology of Motivated Behavior Study Section (NMB)
Program Officer
Meinecke, Douglas L
Project Start
2012-04-06
Project End
2017-01-31
Budget Start
2013-02-01
Budget End
2014-01-31
Support Year
2
Fiscal Year
2013
Total Cost
$370,800
Indirect Cost
$130,800
Name
Northwestern University at Chicago
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
160079455
City
Evanston
State
IL
Country
United States
Zip Code
60201
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