Depression is a complex biological illness.
We need treatments to match.
The latest worldwide 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 (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. But despite this massive investment, only 1 in 3 patients substantially responds to currently available medication or psychotherapy treatments.
Why are we stuck? The modern practices of psychiatry and psychology are grounded in neuroscience and biology. We understand that synaptic connections serve as the currency of neural communication, and that strengthening or weakening these connections can facilitate learning new behavioral strategies and ways of looking at the world. Through studies in both animal models and humans, we have discovered that emotional states are encoded in complex neural network activity patterns, and that directly changing these patterns via brain stimulation can shift mood. We also know that disruption of these delicately balanced networks can lead to neuropsychiatric illness.
Based on this understanding that psychiatric symptoms are rooted in biology, all existing drug therapies for depression target biological mechanisms. Selective serotonin reuptake inhibitors (SSRIs) bind to the serotonin transporter, leading to increased serotonin concentration in the synaptic cleft and a cascade of downstream functional and structural consequences. Although the exact mechanism of action of the fast-acting antidepressant ketamine is still being investigated, it is known to be an NMDA-receptor antagonist. Brexanolone, which is the newest FDA-approved antidepressant for the indication of post-partum depression, is a neuroactive steroid that is a positive allosteric modulator of the GABA receptor. We have now even solved the crystal structures of psychiatric drugs binding to their targeted receptors. Since at least the 1960’s, with the first indications that alterations in levels of catecholamines such as dopamine can lead to depressed mood, we have known that depression is biologically based, and that treatments need to address these underlying biological problems.
Yet, these biologically based treatments are not being matched to the biology of the human beings they’re being used in. According to standard treatment guidelines currently recommended by the American Psychiatric Association, the first-line pharmacotherapeutic treatment for depression is a randomly selected SSRI. And if that doesn’t work, the next step is switching to another randomly selected SSRI, followed by augmentation with an additional agent or switching to an alternative medication class. It is a brute force process guided almost exclusively by qualitative data and subjective self-report. And the impact of each new medication change can take between 2-6 months to assess. 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.
What needs to change? To make meaningful change, we need to match treatments to the specific biology of the people receiving them.
Program goals.
Program Director.
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.
Who are eligible Wellcome Leap program performers?
Performers are from universities and research institutions: small, medium and large companies (including venture-backed); and government or non-profit research organizations. We encourage individuals, research labs, companies, or small teams to apply in program areas best aligned with their expertise and capabilities. It is not necessary to form a large consortium or a single team to address all thrusts or an entire program goal in an abstract or proposal. Indeed, one of the benefits of our programs is that we actively facilitate collaboration and synergies dynamically among performers as we make progress together toward the program’s goals.
Process and timeline
Program announcement.
30 DAYS FOR PREPARATION AND SUBMISSION OF ABSTRACT
15-Day Abstract review round.
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Day 1
Submission deadline: 22 July 2021
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Day 1
Submission deadline: 22 July 2021
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Day 1
Submission deadline:
22 July 2021
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Day 13
Abstract feedback sent: 4 August 2021
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Day 13
Abstract feedback sent: 4 August 2021
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Day 13
Abstract feedback sent:
4 August 2021
30 DAYS FOR PREPARATION OF FULL PROPOSALS AFTER ABSTRACT FEEDBACK
30-Day Full proposal review round.
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Day 43
Submission deadline: 3 September 2021
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Day 43
Submission deadline: 3 September 2021
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Day 43
Submission deadline:
3 September 2021
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Day 71
Proposal decision sent: 1 October 2021
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Day 71
Proposal decision sent: 1 October 2021
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Day 71
Proposal decision sent:
1 October 2021