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Wellcome Leap: Unconventional Projects. Funded at Scale.

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$50M PROGRAM

MCPsych

Multi-Channel Psych (MCPsych) aims to develop an integrated model of anhedonic depression that captures both internal biological factors and externally-manifested, quantifiable measures. The program also seeks to reveal biological mechanisms of anhedonia by synchronizing investigations across genes, molecules, cells, animal models, and humans.

Depression is a complex biological illness. We need treatments to match.

Why are we stuck?

The latest survey of global health underscores the devastating impact of depression. Depression was ranked as the 3rd highest cause of disability across all illnesses, resulting in approximately 43 million years lost to disability. In only a single year, 264 million people suffer from depression, and 800,000 lives are lost to suicide.

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. But despite this massive investment, only 1 in 3 patients substantially responds to currently available treatments.

Rapid stratification and patient-specific matching to the most promising treatment option would reduce adverse effects and prevent progression. Currently 33% of depressed people have significant symptom reduction with the initial treatment selected, while an additional 21-33% of people require between 2-4 treatment trials to achieve remission.

MCPsych has the goal of doubling the number of people who receive an effective treatment on the first try.

In addition, the program seeks to reveal mechanistic understanding sufficient to identify effective treatments for half of non-responsive patients and have the same impact on the survivability of severe, treatment-resistant depression that advances in diagnostics and treatment have had on the survivability of certain cancers. Namely, that in the future, it will be possible to help 85% of people survive their suicidal anhedonic depression for at least 5 years – and perhaps a full lifetime – after diagnosis.

Since at least the 1960’s, we have known that depression is biologically based, and that treatments need to address underlying biological problems. We understand that synaptic connections serve as the currency of neural communication and that emotional states are encoded in neural network activity patterns. Changing these patterns can shift mood and disruption of these delicately balanced networks can lead to neuropsychiatric illness. Modern practices of psychiatry and psychology are grounded in this understanding of neuroscience and biology. However, today clinicians must rely on brute force processes guided almost exclusively by qualitative data and subjective self-report. This current state of affairs leads to time lost for both patients and their loved ones, unnecessary side effects, discouragement, and – perhaps most importantly – continued progression towards end-stage illness.

“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.

Depression can be a terminal illness, just like breast cancer. Rapid, targeted intervention is therefore vital to prevent progression.”

— Regina E. Dugan, Wellcome Leap CEO

Program Director.

Susanne Ahmari
Susanne Ahmari, MD, PhD is a practicing psychiatrist and neuroscientist with expertise in translating findings between humans and model systems. She uses a variety of advanced technical approaches to manipulate and monitor circuits to investigate mechanisms underlying mental illness, including the neural substrates of obsessive compulsive disorder. She established the Translational OCD Laboratory in 2013 to conduct interdisciplinary research that will lead to better treatments for patients. She earned her MD and PhD in Molecular and Cellular Physiology from Stanford University and completed her residency in Psychiatry at Columbia University.

Further details.

To learn more about the program history, performer teams, and process, please visit the Program Details Page.

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