Home » Blog » Alliance Discussion with Dr. Cara Altimus, Dr. Daniel Pham, and Dr. Emily Baxi: BD2 is Redefining the Research Ecosystem for Bipolar Disorder

Alliance Discussion with Dr. Cara Altimus, Dr. Daniel Pham, and Dr. Emily Baxi: BD2 is Redefining the Research Ecosystem for Bipolar Disorder

It has been just over one year since the launch of BD2: Breakthrough Discoveries for Thriving with Bipolar Disorder. BD2 is a philanthropically driven nonprofit initiative that seeks to develop effective interventions so that all people with bipolar disorder thrive. To shorten the time it takes from research findings into clinical care, BD2 has awarded over $60 million of funding to researchers, scientists, and clinicians to build a community focused on enhancing collaboration and open science across the teams. We featured Dr. Cara Altimus, Dr. Emily Baxi, and Dr. Daniel Pham to discuss the numerous mechanisms to encourage collaboration within the network to accelerate change in the bipolar disorder field. Here are some of their thoughts on:

How bipolar disorder is best described and how bipolar affects the population:

Dr. Altimus: “Bipolar disorder is a psychiatric illness that is characterized and defined, in a more medical sense, by changes in mood. It’s divided generally into bipolar type one and two. Those with bipolar one, have experienced at least one manic episode that lasted for longer than a week and generally also experienced depression. Those that have bipolar two have experienced longer major depressive episodes, and generally hypomania rather than a full one week or longer of a manic episode. While we generally characterized bipolar based on changes in mood, we know that people with bipolar have many other domains of symptoms that impact and are part of the disorder – changes in energy levels and sleep function, changes in cognition. We understand that bipolar is much more heterogeneous and this heterogeneity is a very important part of how we need to develop treatments, design the research ecosystem, and think about creating a world that all people with bipolar can thrive. Bipolar is thought most typically is a collection of disorders, rather than a spectrum disorder.”

“Three percent of adults experience bipolar [disorder]; in total, that’s about 40 million people worldwide, and fewer than 50% of people with bipolar are able to find and stay on treatments that that help manage the disorder. Like many neurological disorders and psychiatric conditions, we see a very long delay for correct diagnosis. This is especially important in bipolar, because if left untreated, it’s known to worsen over time.”

The mission of BD2:

Dr. Altimus: “When we look forward, what do we hope that BD2 is able to change in the world? We are first and foremost looking to make sure that we’re driving towards treatments, ways that everyone living with bipolar can live a healthy and full life, and that first in class treatment happens regardless of location. As we look at the whole ecosystem, BD2 is able to bring community together, not just around researchers and clinicians, but also the people living with bipolar and other funders. BD2 is funded by philanthropy. We’ve been able to move as quickly as we can because we had three founding funders come together, and in doing that, we are not only deepening the understanding of bipolar and the mechanisms that are driving the disorder, but we’re also bringing together researchers, clinicians, individuals with lived experience, to drive there are research agendas, develop improved care guidelines, carry the findings back into our care centers to advance clinical outcomes.”

BD2 initiatives and theory of change:

Dr. Pham: “BD2 is made up of four initiatives. The Discovery Research grant programs are funding for collaborative teams to examine causal biological mechanisms ranging from mitochondria, sleep, circadian genetics, and treatments. The Genetics and Omics Platforms are looking at the genetic and molecular components contributing to bipolar. These basic to translational research findings are feeding into what I would consider our engine of change, which is the Integrated Network – the combination longitudinal cohort study embedded in a learning health network that allows data from the longitudinal study to be collected in a central repository, and most importantly, given back. This is really our theory of change – the data is given back to our clinicians to help inform clinical care, it’s given back to researchers to make new discoveries, and it’s also given back to participants to empower themselves with their own data. The takeaway here is that we’ve intentionally built an initiative that puts collaboration front and center, using open science as a tool to help close the research and clinical gap.”

How BD2 is empowering collaboration and enabling open science:

Dr. Pham: “Collaboration in science allows for rapid exchange of ideas, builds on relevant expertise, and sparks innovation. So, we have two main ways to empower collaboration among our funded teams. We’ve built a virtual community platform called the BD2 hub, and this allows all funded teams from the lead PIs to the graduate students and the postdocs to really connect with each other, share data, share resources, and learn from one another. We’re also setting up interest groups that bring groups across the network to share new unpublished data, discuss recent field wide publications and interest areas. To further incentivize collaboration, we’re also implementing collaboration grants. These are one year $150,000 grants that are available to funded teams to form new collaborations across the network so that these collaborations are organic, and not from the top down.

“Open science has been a tool that we are using to accelerate research and care. Open science can produce more rigorous science and stretch research dollars. BD2 has set up a data coordinating center, that Integrated Network is collecting a massive trove of data which is aggregated and standardized. Additionally, we also have a robust open science policy which mandates open science practices to all of our founding teams. So, all the research data code and protocols to assess publications must be open access.”

The BD2 Integrated Network:

Dr. Baxi: “In terms of the Integrated Network, […]it’s a network of clinical sites working together to study bipolar disorder, but also simultaneously learn how to improve care for people living with bipolar disorder. The concept of the Integrated Network is quite novel and emerged in direct response to the needs of the field. There is a need to better understand the heterogeneity and trajectory of bipolar, and to better predict mood changes and responses to treatment as well. Beyond that, it’s really the need to disseminate those learnings and broadly drive advancements in care as rapidly as possible. So, we developed a two-prong approach – a longitudinal study with in-depth clinical and biological profiling, and a learning health network to accelerate the implementation of evidence-based care. What I want you to take away is that we are using all the tools that are currently available to us from clinical assessments, rating, imaging, and bloodwork, even digital tracking, to create these very in-depth biological and clinical profiles of the people who are coming in to participate in this research study.”

The disconnect in attention paid to bipolar disorder and its significance as a health threat:

Dr. Altimus: “It’s been a couple of years, but we did a comprehensive analysis of the funding going to bipolar disorder and other psychiatric conditions and what we found was that funding for bipolar disorder was increasingly happening through broader mental illness efforts rather than focusing specifically on bipolar. We think that that’s important funding, but we also found that when you compare that to disorders like major depressive disorder or schizophrenia, there was much less dedicated to bipolar.”

How can AI impact research in the bipolar disorder field:

Dr. Baxi: “There are so many ways [AI can impact bipolar research], and I think we want to be open to them all. I think there are tools that can help physicians in their quest to be better and faster at diagnosing, but we want to think of them as augmentative and not as a standalone. We are putting apps on participants’ phones that can help create that connectivity between the participant, how they’re doing from year to year. Each year the participants will come back for a comprehensive evaluation – what has been going well, what has not been going so well – but we want to have frequent connection points so we can ask some of the more meaningful questions and conduct some of the measures that will inform that. There are many routes to including AI that are not yet part of what we’re doing but we’ve certainly paved the way for collecting data and making that amenable to AI. Once we’ve aggregated data, that’s where the fun really begins because we’re bringing all these different modalities together to learn something, that I think we can’t learn from each individually. So, using AI to interrogate those datasets, to generate insights will be absolutely key to how we map out the next steps, how we convert the knowledge that is gained through the studies into clinical change, relevant change at the clinical practice level.”

How do racial disparities manifest in the diagnosis, care, and treatment of individuals with bipolar disorder:

Dr. Pham: “This has always been an issue. I think it’s endemic to our health care system and it’s no different in this area, especially with mental health. I think for me as a Vietnamese immigrant living in America, my family doesn’t talk about mental health as an issue, let alone severe mental illness, such as bipolar, right? So, we don’t even seek out the services, let alone try to access any treatments that oftentimes are done based on clinical trials that severely lack diversity. So, the treatments may not even work for us even if we do seek it and I think that that’s a huge issue. I think BD2 is focused on [diversity] throughout the spectrum. For Genetics and Omics RFAs (request for applications), when we release them, there is very clear intentionality of asking all the applications to send in a roster of all their samples, and they’re breaking down sex, gender, ethnicity, race, etc., so that we have a better understanding of what exactly are the samples that are being put into the system. For the genetics work, we’re sequencing about 30,000 samples, all of whom are of non-European ancestry, so immediately addressing some of that racial disparity in the science.”

What do you envision as the best outcomes for BD2 initiatives addressing bipolar disorder:

Dr. Altimus: “We’re trying to bring the future not just as close to now as possible but look at what we can change now and for whom and where and for the most people. So, to merely highlight the way the Integrated Network has been designed, and the way that we’ve brought clinicians to the forefront of how we’re bringing science together, is intended to improve outcomes and science for people today, as well as continue to push to include more and more people over time in the future.”

Dr. Baxi: “I think it’s really that sense of using the tools that we have today in the best possible way and making sure that all those caring for people with bipolar disorder know what those [tools] are, but then building the tools for tomorrow. I think that the Integrated Network and the Discovery Grants are recognizing what a cohesive force of change that needs to become a reality. It takes clinicians, physicians, people with the lived experience, everyone to understand and to push the boundaries of our knowledge so we have better interventions and strategies in the future.”

Dr. Pham: “This has been such an exciting initiative to really think outside the box and be greater than the sum of our parts. Especially going back on the power of philanthropy and playing outside of the traditional roles of government and how that can be an example of how government can play a role too. So, again we still are very much working with NIMH and other entities to just make sure we all understand our roles and how we could all just accelerate change for people living with bipolar.”

Watch the full discussion here. View the presentation slides here.