Multi-Channel Psych: Revealing Mechanisms of Anhedonia

Funding Agency:
Wellcome Leap

The latest worldwide survey of global health underscores the devastating impact of depression.i Depression was ranked as the 3rd highest cause of disability across all illnesses, resulting in approximately 43 million years lost to disability (YLD). In only a single year, 264 million people suffer from depression, and 800,000 lives are lost to suicide. Narrowing in on the United States, almost 7% of adults experience an episode of depression each year, costing an estimated $210.5 billion due to the combination of treatment costs and productivity loss. Consistent with this enormous disease burden, the NIH has spent over $22 billion on depression research over the last 20 years – more than for any other mental illness, including addiction, schizophrenia, or autism.ii But despite this massive investment, only 1 in 3 patients substantially responds to currently available medication or psychotherapy treatments.

To make meaningful change, we need to match treatments to the specific biology of the people receiving them. But when field experts are presented with this challenge, three gauntlets are typically thrown down. First, there is a lack of easy access to the biological substrate of depression – i.e., the brain – which makes it difficult to determine pathologic mechanisms. Unlike in the field of cancer, the brain is not easily biopsied, and even if it could be, the abnormalities leading to symptoms are likely distributed over broad neural networks. Second, it can be difficult to tell when treatments for depression are working due to noise in the system. As opposed to determining quantitatively if a tumor has shrunk, treatment efficacy for depression relies on subjective self-report. But any practicing clinician will tell you that family members often notice changes in symptoms such as psychomotor slowing and affect even before patients do themselves. And the third, most daunting gauntlet is – It’s Just Too Complex. Depression is a heterogeneous disorder, with an unknown number of different subtypes that may have different treatment responses. The brain is an incredibly complex organ that is composed of an unknown number of different cell types, intricately networked together to supervise all of the body’s functions. The brain is situated in the body, which in turn is situated in the world. And the two major collective traumas of 2020 – the COVID-19 pandemic and systemic racism – have made it all too clear that the body and the world can directly impact the brain, leading to depression. The barriers are evident. So, it is now time for the field to take up the gauntlets together, and take down these obstacles.

We envision a world in which diagnosing anhedonic depression is as straightforward as getting a mammogram, and stratification into a treatment plan has the same speed as current algorithms after breast biopsy. This necessitates a general shift of mindset in an important way. Depression can be a terminal illness, just like breast cancer. Rapid, targeted intervention is therefore vital to prevent progression. Initially selecting the treatment with the highest likelihood of working for an individual patient based on their specific biology is therefore of high value, because in addition to decreasing the total time of suffering, key goals include avoiding unnecessary side effects and limiting treatment-associated risks.

Deadline for Abstracts: July 22, 2021

Duke University is a member of the Wellcome Leap Health Breakthrough Network. Faculty interested in this opportunity should contact Jennifer.Gallina@duke.edu and Vera.Luck@duke.edu for additional information before applying.

Agency Website

Areas of Interest

We are soliciting abstracts and proposals for work over 3 years (with a potential additional one-year option) in one or more of the following thrust areas. Proposers should clearly relate work in these thrust areas to one or more of the program goals.

  • Thrust Area 1: Identify biological markers of mechanistic causes of anhedonic depression
  • Thrust Area 2: Quantify symptoms objectively and with high frequency
  • Thrust Area 3: Develop end-to-end model(s) of anhedonic depression

Eligibility Requirements

Performers from universities and research institutions: small, medium and large companies (including venture-backed); and government or non-profit research organizations are invited to propose. 

Funding Type

Grant

Eligibility

Faculty

Category

Environmental & Life Sciences
Interdisciplinary
Medical
Medical - Basic Science
Medical - Clinical Science
Medical - Translational

External Deadline

July 22, 2021