About This Project

Of the 300 million people worldwide living with depression, half do not respond to current treatments. In this population, most undergo forms of early life stress (ELS). Our group is interested in examining the impacts of ELS on the brain areas and pathways later implicated in depression. We hypothesize that ELS could cause longstanding changes in cortical and limbic cells and pathways. Understanding these impacts could lead to novel treatments both behavioral and pharmacological.

Ask the Scientists

What is the context of this research?

Our understanding of depression still has several missing pieces, and the causes are not fully understood. One subset of people living with depression undergo stressful experiences during early childhood, and show altered brain activity as adults. Additionally, depressed patients tend to have a bias in their attention and appraisal of incoming information, attending to only the negative information. While the clinical link between ELS and depression is robust, its neurobiology is gravely understudied. We intend to move this research forward, by deciphering how ELS rewires brain areas linked with depression. We will use an animal model of ELS and assess depressive behaviors and cognitive bias in adulthood, and examine their neural connectivity and function.

What is the significance of this project?

Of the 17 million affected Americans living with depression, almost half are unresponsive to current treatments. ELS is a large risk factor in this subgroup. An issue that we see in depressed patients and in animal models of depression is a decrease in the number and diversity of neural connections. This decrease has been linked with adult stress in animal models. We will test the hypothesis that ELS reduces neural connectivity, neuronal function, and elicits depressive behavior. Testing this hypothesis will define the role of ELS in the etiology of depression. Significantly, it will mobilize a research program aimed towards behavioral and drug treatments that restore neuronal connections.

What are the goals of the project?

These experiments will demonstrate the impact of ELS on two brain areas implicated in depression, as well as on behavioral outcomes in depressive symptoms and cognitive-affective bias. Our studies examine ELS impacts compared to controls as well as adult stress groups, currently used as an animal model of depression. Electrophysiology experiments will determine differences in cell physiology, in presynaptic and postsynaptic function. IHC will illustrate disparities in relation to cell morphology and dendrite architecture. Behavioral assessments will compare the different stress groups in depressive phenotyopes and cognitive bias. The outcome would be a novel understanding of the neurobiology of depression that could to give new potential targets for treatment.