Pilot awards offer early- and mid-stage career faculty an opportunity to collect key pilot data—with a particular focus on innovation—with the goal of identifying the underpinnings of depression and anxiety, and developing new targets for treatment both for individual patients and on a public health scale. These preliminary data, in turn, are utilized to pursue additional funding.
The below pilot awards have been made possible by the generosity of the Saks Fifth Avenue Foundation, whose mission is to make mental health a priority in every community.
2021 Depression Center Pilot Awards
Sarah Canetta, PhD
Understanding the Behavioral Efficacy of Tianeptine in a Model of SSRI Resistance
Although selective serotonin reuptake inhibitors (SSRIs) are frontline treatments for depression, they are ineffective in approximately 40% of patients. This project will use a translational model of SSRI resistance, in which the atypical antidepressant tianeptine remains effective, to define the neurophysiological and behavioral mechanisms underlying different antidepressant pharmacotherapies, as well as improve our understanding of why they can be differentially effective in certain individuals.
Alexander Harris, MD, PhD
Enhancing Resilience with Behaviorally Driven Reward Circuit Stimulation
The rising rates of depression in the United States highlight the need for interventions that will build resilience. Reward seeking deficits at baseline predicts the future development of depression. This project will use behaviorally driven stimulation of reward circuitry to artificially enhance baseline reward circuit responses to rewards. We anticipate that this powerful approach will confer resilience and pave the way for future circuit-based treatments.
Bin Xu, PhD
Identify the Effects of Ketamine on Neural Cell Type Specific Signaling Pathways
Although there are abundant clinical studies confirm that ketamine has a remarkable rapid-onset antidepressant effect, the mechanism of action of ketamine's rapid antidepressant effect is still largely unknown. With the recent development in stem cell base tissue engineering, the human induced pluripotent stem cell-based brain organoid model is providing sufficient diversity in cell types and projections to mimic the in vivo human brain tissue context for modeling the response of different cell types to ketamine exposure. Therefore, this project proposes to identify key pathways and regulators in each cell type affected by ketamine using brain organoid model combining with single cell transcriptome analysis, genome wide epigenetic analysis, and proteomics.
2020 Depression Center Pilot Awards
Maura Boldrini, MD, PhD
Brain Single Nuclei Transcriptomic Biosignatures of Major Depression and Antidepressant Action
The project aims to test which genes have altered expression in major depressive disorder and which ones are normalized in antidepressant-treated depression. Ultimately, genes that are not modulated by the currently available antidepressants could become new treatment targets.
Claudia Lugo-Candelas, PhD
Clarifying Neural Circuity related to Inhibitory Control in Adolescent Suicide Attempters
Presently, the neural correlates of adolescent suicide are unclear. The project will use resting state MRI to test whether neural circuitry related to inhibitory control differences suicide ideators versus suicide attempters.
Elizabeth Sublette, MD, PhD
Linking the Microbiome to Inflammation and Major Depression
Using deep metagenomics, the study investigates both gut and saliva microbiome to study microbial relationships across body sites as well as the relative strengths of their relationships to peripheral and central inflammatory indices. The oral microbiome is understudied with respect to the central nervous system; associations have been reported with migraines, but we are not aware of studies in depression.
Ardesheer Talati, PhD
Early Life Vulnerability to Depression: Establishing a 4th Generation Cohort from a Multigenerational Family Study of Depression
This pilot project aims to characterize a 4th generation of offspring from an ongoing, richly characterized multigenerational study of depression, focusing on early childhood environment and proinflammatory markers in these at-risk offspring while they are still young, before onset of psychopathology.
2019 Depression Center Pilot Awards
Christoph Anacker, PhD
Identifying Novel Diagnostic Biomarkers of Depression Risk
The goal of this study is to investigate neural circuit dysfunction and blood-based biomarkers for depression risk in humans with a family history of depression. In collaboration with Dr. Myrna Weissman, we are utilizing a 4-generation family cohort of high risk for depression to identify neural circuit dysfunctions and molecular abnormalities that may precede depression in at-risk individuals, to better understand the pathogenesis of depression and to identify potential biomarkers for early diagnosis. We are combining this clinical approach with rodent mouse models in which we can functionally manipulate the same neural circuits that we identify in humans to test their causal role for brain function and behavior.
Randy P. Auerbach, PhD
Improving the Short-term Prediction of Suicidal Behavior in Mood Disorders
Presently, our ability to predict the emergence of suicidal behaviors is limited. The pilot project seeks to leverage smartphone technology to clarify real-time markers—through experience sampling and passive sensor digital phenotypes—to predict suicidal behaviors among high-risk adults with a history of mood disorders.
Bradley Miller, MD, PhD
A Pilot Study of a Novel Major Depression Associated Mutation: Bridging the Gap from Mutation to Behavior
Dr. Miller and his research team discovered a human mutation in an orphan GPCR strongly associated with major depression and generated a mouse model of the mutation that shows enhanced sensitivity to stress. The pilot study aims to determine how the mutation alters brain activity in vivo during emotional behaviors.