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.
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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.
We are requesting funding to cover laboratory supplies, core facility fees and animals costs to carry out the proposed research project. Research supplies are calculated at approximately $10,060 throughout the project period, and include reagents for electrophysiology and immunohistochemistry studies as well as confocal microscopy user fees. Animal Costs (mice colony) costs are calculated at approximately $2,400 throughout the project period, and include housing, keeping, tagging and genotyping.
We began collecting data in early January 2021. We are using a minimal number of animals, and will get multiple data points from each animal. The first set of experiments will complete the behavioral tests as well as the electrophysiology. These data points are connected, and finish about the same timeline. Once that is complete, we will concentrate on morphology/IHC, and finally we will assess cortisol differences and sex differences from blood and swabs taken at sacrifice.
Mar 15, 2021
May 15, 2021
Complete Behavioral assessments for each group. Illustrate any differences (or similarities) between controls and stress groups.
May 31, 2021
Complete electrophysiology and data analysis on Input/output and frequency tuning.
Jul 31, 2021
Complete IHC and data analysis on dendrite architecture and cell counts in areas of interest.
Meet the Team
My research interests are focused on the neurobiology of various mental health issues. In past projects I have worked on trauma, in both animal models and in human studies. As a licensed psychotherapist in NYC, I work with people with many different mental health issues, some of which are unresponsive to both pharmacological and behavioral treatments. These clinical stories are a major component that drives my passion for research, as the deeper understanding of the biological and cognitive underpinnings of these disorders could lead to novel treatments in pharmacology and psychotherapy.
Currently my interests are in the underlying neurobiology involved in depression and cognitive-affective bias. Neither of these topics are well understood, and roughly half of depressed patients do not respond to typical treatments. In these clients, we see a relationship between treatment resistant depression and adverse childhood experiences (early life stress), suggesting that stress early in life could lead to persistent biological changes. These changes may impact depressed mood and impact cognition as well, as negative attentional bias (cognitive-affective bias in animal behavior terms) is a common feature in depression. By examining the direct impact of ELS on an animal and exploring behavioral and biological outcomes, we can further expand our understanding of the neurobiology of depression- an enterprise that could lead to helping millions of people from novel treatments.
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