Michael Berk, MD, PhD

“Brain health conditions are a key contributor to the global burden of disease and disability. The devastating impact of these conditions is even more apparent as the world faces global challenges such as the COVID-19 pandemic, climate change, societal inequity, and more. To make progress, we need a fundamental shift in our approach. Convergence Brain Health deftly makes the case that a convergence approach is urgently needed to tackle the global brain health crisis and provides a roadmap for change.”

— Victor Dzau MD, President, National Academy of Medicine

Even before the COVID-19 pandemic, the world was in the midst of an escalating global brain health crisis with severe physical, social, and economic ramifications. According to a recent World Health Organization report, around 450 million individuals were suffering from mental health conditions, marking mental health disorders among the leading causes of ill-health and disability worldwide.

 The Organisation for Economic Co-operation and Development (OECD) estimates that the consequences of mental ill health cost up to 

Due to social and physical distancing, unemployment and underemployment, stress and other factors, there have been significant increases in issues such as depression, anxiety, social isolation, substance abuse, loneliness, and cognitive decline in older adults.

 In addition, as observed after the SARS pandemic, it is expected that COVID-19 survivors may endure long term cognitive and psychiatric consequences, including suicide, posttraumatic stress disorders, and depression.

 Furthermore, brain health is a prototypical 

 in that it is extremely complex and textured by innumerable variables from biology, sociology, genetics, psychology, and the natural environment to economics and beyond.

 Compounding these issues are challenges at all levels of innovation around brain health, listed in 

Table 1. Challenges and Opportunities for the Brain Health Field

Progress in the 21st century will be molded by our collective response to the global brain health crisis.

 Fortunately, beacons of hope are beginning to shine. Stigma has been reduced in high-income country settings, allowing individuals to overcome the barriers to seeking care.

 The COVID-19 pandemic has—in a positive sense—lowered the perceived and actual barriers to technology adoption, ushering in a new era of technology-driven brain health care. Some governments are beginning to increase spending on brain health, and venture capital funding for brain health start-ups has never been more in vogue. PitchBook data shows that 146 deals generated nearly $1.6 billion in venture capital investments as of December 10th, 2020. A decade ago, there were only 3 deals, worth $6.6 million, whereas last year saw a total of 

However, these advances on their own cannot solve the myriad global challenges posed by the brain health emergency. A paradigm shift is needed to address the unprecedented complexities associated with the current global brain health crisis—a crisis now inextricably linked to concurrent interacting crises surrounding discrimination and inequality, mass misinformation, environmental catastrophes, accelerated climate change, entrenched economic models, population displacements and immigrant status, and more.

 Governments, employers, and healthcare systems around the world need to acknowledge the scope of the problem and embrace solutions to empower consumers to take charge of their own brain health and to protect existing levels of health, well-being, and social inclusion.

In response to the evolving issues, convergence science integrates knowledge, tools, and thought strategies from diverse fields to address challenges that exist at the interface of 

 Convergence science not only recognizes the need to respond to apparent societal problems, but also emphasizes approaches which allow us to consider a myriad of the known unknowns and improves the odds of us quickly adapting to newly identified gaps.

 Acknowledging the serendipity of accidentally obtained knowledge permits 

 Taking these approaches when investigating solutions to brain health challenges permits greater flexibility and utility when unforeseen challenges are inevitably met.

Brains are the indispensable drivers of human progress. Why not invest more heavily in them? There are currently 

 allocated to Environment, Sustainability, and Governance investing around the world.

 If only a portion of this amount were invested in brain health, we could produce major improvements for our society.

 note that this present moment is a clarion call for the philanthropic community, which is uniquely positioned to lead an approach in 2 distinct ways. In the short term, the immediate mental health crisis can be mitigated by supporting interventions for the most vulnerable, the development and deployment of rapidly available mental health tools and technologies, and research to drive evidence-based responses to COVID-19-related mental health challenges. Much work is needed to address the long-term mental health impacts caused by the pandemic. There is an ongoing and urgent need for targeted investment in research to better understand and treat mental health conditions, build capacity and diversity within the mental health system, and advocate for social and policy solutions to improve the ecosystem of mental health care.

Given the critical need to nurture healthier, more resilient, and increasingly flexible brains worldwide, we have introduced the concept of Brain Capital—broadly defined as a form of capital which prioritizes brain skills and brain health.

The OECD Neuroscience-inspired Policy Initiative seeks to place Brain Capital at the center of a new narrative to fuel societal resilience in mitigating economic shocks, and to create preparedness should future societies fundamentally transform, for instance through irreversible damage to the environment. The OECD’s New Approaches to Economic Challenges Unit has created the Neuroscience-inspired Policy Initiative. This initiative seeks to reconceptualize and revitalize the economy, laying the groundwork to identify relevant metrics while building a transdisciplinary network of stakeholders. The initiative will rapidly refine and advance the concept of Brain Capital via a series of research projects, economic modelling, seminars, and clear policy analyses and recommendations.

In this context, our Brain Capital Grand Strategy supports the focus of the OECD initiative. The Grand Strategy has 3 main components: considering Brain Capital in all policies, developing a comprehensive investment plan to support Brain Capital, and generating a Brain Capital Index.

Brain health issues should be addressed in the context of improving performance within the fields of innovation and entrepreneurship. Because most 

 are created by firms less than 5 years old,

 creative and innovative entrepreneurs are needed to drive social and economic growth at the regional and national levels. In many ways, together with unprecedented government investment in many countries, entrepreneurs stand as a critical firewall against recession and deprivation. They serve as economic first responders when (exogenous) catastrophic events produce national and global economic shocks. 

In the United States, deaths due to suicide, opioid overdoses, and other addictions and poisonings (deaths of despair) are a barrier to complete economic recovery from COVID-19.

 Approximately 20% of prime-aged males who have dropped out of the labor force are 

 in these deaths, and many of them will not take up jobs even when available due to the severity of their addiction.

A senior economist at The Brookings Institution is leading an initiative to coordinate the many efforts to deal with this crisis. An important role for the task force would be to coordinate with the many burgeoning local level efforts to address addiction and despair, and these local organizations could greatly benefit from ties to a federal-level coordinating agency. Among other things, this agency could serve as an 

 Without addressing the linked issues of mental health and labor market drop-out simultaneously, it will be difficult to solve the tragic mental health crisis or achieve the goal of widely shared economic prosperity.

It is also essential that, given the complexity of the challenges being addressed, freedom to fail is offered liberally. Flat organizational structures, which are agile and empower individuals to make decisions in their specific areas and roles without need to constantly consult with managers at higher levels, are important. However, these decisions should be aligned with the mission and not deviate from the already traced goals and strategy. In 

, we provide examples of organizations and buildings which foster Convergence Brain Health activities.

Table 2. Infusing Convergence Brain Health Practices Into Various Levels of Innovation

Existing models of innovation are not adequate—suffering from siloing and a lack of speed. There are now a number of more contemporary models which may propel the brain health field forward more quickly and effectively. 

For example, The Davos Alzheimer Collaborative (DAC) is a public-private partnership committed to a collective global response against the challenges Alzheimer disease presents to millions of families around the world.

 The DAC aims to raise around USD $700 million for a 6-year plan to accelerate and diversify innovation in Alzheimer disease research. The 3 main components of DAC include a global cohort developed to identify new targets for potential treatments, a global clinical trial support platform to reduce the cost and time to bring new treatments to market, and a healthcare system prepared to get new treatments to patients. The DAC project will enable novel biomarker development, connect global researchers using the data platform provided by the Alzheimer Disease Data Initiative, and keep individuals with the lived experience of Alzheimer disease at the center of its efforts.

The first big data wave occurred over a decade ago, fueled by the reduced cost of -omics techniques (eg, genomics, transcriptomics), increased access to neuroimaging equipment, and the transition to electronic medical records. Insights from this data, however, have not translated into dramatically improved outcomes for patients. Diagnostic clarity is often elusive and treatment selection remains primarily trial-and-error. A second wave of big data proliferation is already underway with the increased implementation of mobile applications and wearable devices.

 Solutions are desperately needed to resolve current bottlenecks in transforming data into insights and action. 

Furthermore, according to economist Klaus Schwab, PhD, we are on the verge of the Fourth Industrial Revolution, which will see a rise in cyber-physical systems that blur “the lines between the physical, digital, and biological spheres.”

 Virtual reality environments, brain-computer interfaces, wearable or implantable devices, and mobile applications will continue to contribute to the current data explosion. Artificial intelligence integrates knowledge from a myriad of disciplines, including computer science, data science, mathematics, engineering, physics, statistics, linguistics, signal processing, ethics, and philosophy. Artificial intelligence is no longer a novelty, but a requisite set of convergence tools for navigating the future.

As psychological disorders are mediated by complex interactions between genetic and environmental factors it will be imperative to dedicate significant effort to understanding the modifiable risk factors emerging from the environment.

 Since the environment includes biological, psychosocial, and ecological components, it is likely to be more complex than the genes, proteins, and metabolites that are currently analyzed by a variety of tools. Therefore, within the framework of convergence brain health it will be necessary to develop highly powerful and complex tools that record, measure, and analyze the myriad environmental factors. This effort will be pursued as it has been with the omics technologies but with a much larger scope, ranging from psychophysiological data collected from millions of individual smartphones to satellite tracking of air pollution in big cities. Important ethical issues, however, will have to be addressed with some urgency.

Operationalizing a convergent clinical framework will require effective direction and utilization of the continuing data explosion.

 The role of digital clinical operating systems is therefore critical for allowing effective patient care, as well as ongoing research. These clinical operating systems house data from clinical encounters, imaging, pathology, personal medical devices, wearables, and finance. Analytics methods include the use of mathematical and algorithmic-based processing of data resources, including subfields of artificial intelligence, such as machine learning, natural language processing, and visual analytics to generate descriptive, predictive, and prescriptive models to analyze and derive insight from data. Machine learning has been utilized in predictive risk assessment, clinical decision support, home health monitoring, finance, and resource allocation.

Convergent approaches often require consideration of many different data types. Data harmonization involves creating a single consistent macro-data source from multiple, potentially disparate micro-datasets. Contributing datasets are structured to remove inconsistencies, creating harmony, such that the final dataset provides a cohesive view of a subject from many different perspectives. Machine learning enables automatization of this process, permitting integration of clinical, behavioral, -omic, imaging, neurosignals, and other datatypes for data mining and predictive modelling. Deep learning in combination with multidimensional biological data (eg, genomics, proteomics) enables examination of the impact of genetic variation or other system disturbances on transcription, translation, signaling, and resultant phenotypic variation. 

Perioperative brain health is an emerging example of the need for a convergence approach in brain health science. The average individual undergoes 9 surgical procedures in his or her lifetime, typically at an older age when the brain is more vulnerable to perioperative insults such as stress, illness, and immobility.

 As such, the perioperative period is a very high-risk period for older adults, and brain health impairments are abundant with considerable negative impacts. For example, the US National Health and Aging Trends Study found clinically significant depressive and anxiety symptoms in 39% and 24% older adults in rehabilitation facilities, respectively, in older adults recently in rehabilitation facilities (vs. 10% and 9% for older adults in the community).

Similarly, a study in the UK of postoperative Intensive Care Unit patients found rates of 40% and 46%, respectively.

 Depression and anxiety are connected to poor postoperative outcomes, including persistent pain, delirium, longer hospital stays, poor functional recovery, lower quality of life, and increased chance of both falls and rehospitalization.

A new field of perioperative mental health is responding to the need to integrate mental and cognitive healthcare with surgical and postsurgical care. The increasing number of older adults undergoing surgery creates high demand for this innovation, so that care can move beyond an emphasis only on surgical success and anesthetic safety, to a convergent brain health view of outcomes, such as improved functional recovery, reduced rehospitalization, and decreased long-term morbidity. These innovations are further driven by bundled care models, which include preoperative optimization, in-hospital care, and postoperative rehabilitation. With the recent genesis of the Center for Perioperative Mental Health, funded by the National Institute of Mental Health (P50MH122351), surgeons, anesthesiologists, nurses, physical and occupational therapists, and surgical patients will work together with psychiatrists in an accelerated laboratory for translating scientific advances to practical clinical care that improves the lives of older adults.

With the emergence of so many digital innovations, care providers are presented with more tools than ever. However, such a crowd of novel options adds complexity and uncertainty. To be clinically useful, such point solutions must first be vetted and then clustered into symphonies shown to play well together to optimize collective benefit for specific conditions. In the dementia field, for example, it is encouraging to see multidomain interventions being deployed.39 In the future, a therapeutic guidance system may make sense, similar to those used to advance precision medicine, such as oncology and neurosurgery.

To develop a workforce that can harness and deploy a convergence brain health framework, increased inclusion and empowerment of women and other traditionally under-represented populations is required. Building institutions that are both inclusive and meritocratic is health promoting in its own right. But more importantly, it is a powerful mechanism for producing the additional talent, fresh perspectives, and new ideas that are needed.

Meanwhile, certain behavioral characteristics among individual innovators should be cultivated. MacRae and Furnham

 articulated 3 dimensions of a high-potential individual suited to convergent teamwork building on Silzer and Church’s model of potential.

 There are 3 core dimensions: foundational, growth, and career dimensions. These dimensions explain how personality traits are foundational to potential because they represent fundamental and stable individual differences. Personality traits, especially conscientiousness and adjustment, contribute to success in nearly any type of work and have, “higher predictive ability of potential in roles that are more complex, challenging, and demanding such as that of the convergence practitioner.”

Career dimensions are the unique and specific skills, expertise, and occupational knowledge required for success in a specific career or role: “Convergence practice requires sublimating one’s own objectives into the vision and the objectives of the team.”

 MacRae and Furnham explain in detail how personality traits fit within a model of convergence practitioner potential and expand on 10 behaviors that are related to career dimensions of potential.

 These behavioral and workplace cultural characteristics allow us to formulate screening criteria for potential new entrants into convergent brain health work, identify those who are high potential convergence practitioners, as well as consider training approaches for those within our existing brain health structures.

Leaders must assume a critical role in optimizing transdisciplinary collaboration and facilitating the emergence of discoveries from these endeavors.

 Gray outlined 3 responsibilities of transdisciplinary leaders: cognitive leadership, structural leadership, and processual leadership:

. Effective cognitive leadership provides a vision that links and motivates transdisciplinary researchers to step beyond their disciplinary lens, relax old assumptions, and search for creative frame-breaking solutions.

. Effective structural leadership adds value by creating bridges and links among unconnected individuals, labs, groups, or departments.

- Processual Leadership: Effective processual leadership encourages trust and turns conflict into constructive interactions.

These leadership approaches should be kept in mind when fostering Convergence Brain Health within an organization. Other 

 of a convergence workplace include a flat organizational structure with minimal discipline silos, a culture of trust and mutual respect, and an open acceptance of the need to respectfully challenge entrenched ways of thinking.

 Teams should be humble in acknowledging that nobody has cracked the many complex problems to date, and likely never will due to unsolvable uncertainty. However, being open to novel and seemingly eccentric ideas may help navigate such problems and identify ways for their best possible management.

Teams in a convergence workplace must embrace the three somehow radical tenets outlined in Jim Dator, PhD’s 

: 1) The future cannot be predicted because the future does not exist; 2) Any useful idea about the future should appear to be ridiculous; and 3) We shape our tools and thereafter our tools shape us.

 An optimal convergence science environment should have a strong guiding vision, will be capable of identifying myriad possible alternative futures, and better guide the organization toward the desired future.

Convergence Brain Health provides direction for transformational change in how teams could work and how organizations need to be built and operated. As we embark on building the new normal of our post-COVID-19 world, Convergence Brain Health will play a key role in this rapidly unfolding change. Indeed, Convergence Brain Health provides an opportunity to grow global Brain Capital and enter a new era of innovation and progress, leading to greater health justice for all people and preparing for the unprecedented brain health challenges of the 21st century.

is cofounder of the PRODEO Institute, adjunct associate professor with IMPACT at Deakin University, instructor in brain health diplomacy at the Global Brain Health Institute, and co-lead of the OECD Neuroscience-inspired Policy Initiative.

is Director of Innovation at a major mental health association and expert in residence at Georgetown University, and the author of Wired This Way.

is an associate with the PRODEO Institute and Thiel Fellow at Stanford University.

is a professor of psychiatry at University of California in Los Angeles (UCLA).

is Distinguished and Emeritus Professor of Psychiatry, University of Pittsburgh, Pittsburgh, PA.

is the global head of Science for Minds at Johnson & Johnson.

is a health policy researcher at the Global Brain Health Institute.

is a social gerontologist at the Global Brain Health Institute.

is a research professor and Director of Chambers-Grundy Center for Transformative Neuroscience at the University of Nevada, Las Vegas.

is a venture partner at Alsop Louie Partners.

is professor and vice chair of Psychiatry & Behavioral Services at Baylor College of Medicine.

is special advisor to the OECD secretary general and head of the OECD New Approaches to Economic Challenges Unit.

is the Wallace & Lucille Renard Professor of Psychiatry and the Director of the Healthy Mind Lab at Washington University School of Medicine in St. Louis, Missouri.

is head of strategic projects and alliances at Delix Therapeutics.

is a professor in the department of Integrative Structural and Computational Biology at Scripps Research Institute.

is Head Stakeholder Liaison Alzheimer disease at Biogen.

is a professor of Law and Health Sciences at the University of Surrey School of Law and adjunct assistant professor of Medicine at the David Geffen School of Medicine at UCLA.

is the founding director of the Center for Brain Health at UT Dallas.

is a T. Boone Pickens Distinguished Scientist at the Center for BrainHealth, a co- director at Global Brain Health Institute, professor emeritus at Trinity College Dublin, and founding director of its Institute of Neuroscience.

is the Leo Pasvolsky Senior Fellow at the Brookings Institution, a College Park Professor at the University of Maryland, and a Senior Scientist at Gallup.

is a postdoctoral researcher, Center for Precision Health School of Biomedical Informatics at the University of Texas Health Science Center at Houston.

is Researcher at the Department of Aquatic Sciences and Assessment; Section for Ecology and Biodiversity at the Sveriges lantbruksuniversitet.

is Assistant Clinical Professor of Psychiatry and Biobehavioral Sciences at David Geffen School of Medicine at UCLA and UCLA Olive View Medical Center. 

is a neuroscientist at the Global Brain Health Institute.

MB is supported by a NHMRC Senior Principal Research Fellowship (1156072). MB has received Grant/Research Support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, Medical Benefits Fund, National Health and Medical Research Council, Medical Research Futures Fund, Beyond Blue, Rotary Health, A2 milk company, Meat and Livestock Board, Woolworths, Avant and the Harry Windsor Foundation, has been a speaker for Abbot, Astra Zeneca, Janssen and Janssen, Lundbeck and Merck and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Janssen and Janssen, Lundbeck Merck, Pfizer and Servier – all unrelated to this work. HAE is an employee of PRODEO LLC. ES is an employee of PRODEO LLC. ASC is an official employee of Biogen Int and the VP of Euresearch. Her contribution to this work is based on her personal opinion and might not reflect the one of the organizations with whom she is affiliated. AI has received Grant/Research Support from ANID/FONDECYT Regular (1210195); FONCYT-PICT 2017-1820; ANID/FONDAP/15150012; Alzheimer’s Association GBHI ALZ UK-20-639295; Sistema General de Regalías [BPIN2018000100059] Universidad del Valle [CI 5316], and the Multi-Partner Consortium to Expand Dementia Research in Latin America [ReDLat, supported by National Institutes of Health, National Institutes of Aging (R01 AG057234), Alzheimer’s Association (SG-20-725707), Rainwater Charitable Foundation (Tau Consortium), and Global Brain Health Institute)]. EJL has received support from the NIH, Patient-Centered Outcomes Research Institute, Taylor Family Institute for Innovative Psychiatric Disorders, and Center for Brain Research in Mood Disorders at Washington University.

1. Eyre HA, Berk M, Lavretsky H, Reynolds III C, eds. 

Convergence Mental Health: A Transdisciplinary Approach to Innovation.

2. World Health Organization. The world health report 2001 - mental health: new understanding, new hope. 2001.

3. Organization for Economic Cooperation and Development. Health at a glance: Europe. Accessed May 6, 2021. 

https://www.oecd-ilibrary.org/social-issues-migration-health/health-at-a-glance-europe-2020_82129230-en

4. Holmes EA, O’Connor RC, Perry VH, et al. Multidisciplinary research priorities for the COVID-19 pandemic: a call for action for mental health science. 

5. Blazer D. Social isolation and loneliness in older adults-A mental health/public health challenge. 

6. Vahia IV. COVID-19, aging, and mental health: Lessons from the first six months. 

7. Orben A, Tomova L, Blakemore SJ. The effects of social deprivation on adolescent development and mental health. 

8. Steenblock C, Todorov V, Kanczkowski W, et al. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the neuroendocrine stress axis. 

9. Milner A, King TL, LaMontagne AD, et al. Underemployment and its impacts on mental health among those with disabilities: evidence from the HILDA cohort. 

10. Koralnik IJ, Tyler KL. COVID-19: a global threat to the nervous system. 

11. Varatharaj A, Thomas N, Ellul MA, et al. Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study

12. Mak IW, Chu CM, Pan PC, et al. Long-term psychiatric morbidities among SARS survivors. 

13. Taquet M, Geddes JR, Husain M, et al. 6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records

14. Stony Brook University. What’s a wicked problem

https://www.stonybrook.edu/commcms/wicked-problem/about/What-is-a-wicked-problem

Articles

How can we face the current pandemic while addressing the brain health crisis?  

Boosting Brain Health After COVID-19: A Convergence Solution 

Serendipity has played a significant role in many scientific advancements in mental health throughout history, like the discovery of lithium as a treatment for bipolar disorder. Now more than ever, we are in desperate need of similarly impactful discoveries in mental health. Adopting a serendipity mindset—the ability to use uncertainty as a pathway to a more successful and purposeful life—to reverse engineer the systems needed for more breakthroughs, and to span and fuse disciplines, might be the way to achieve this.

The Leading Cause of Ill-Health and Disability

The world is in the throes of a global mental health crisis with severe physical, social, and economic ramifications. According to a recent World Health Organization (WHO) 

, around 450 million individuals currently suffer from mental health conditions, marking mental health disorders among the leading causes of ill-health and disability worldwide.

 Mental disorders account for 5 out of the top 10 causes of global disability. Although treatments are available, 

 of individuals with a known mental health disorder will never seek help from a health professional.

 Surveys in India and China, which represent a third of the global population, have suggested this number is even higher, with more than 80% of people with any mental health or substance use disorder not seeking treatment. In part, this is due to the pervasive stigma of mental illness that permeates societies and healthcare systems, resulting in systemic underinvestment in mental health.

When individuals do seek help, they may not be able to receive the care they need. According to a recent report from a team of 28 global experts assembled by Lancet, the world’s failure to respond to the mental health crisis has resulted in a “

monumental loss of human capabilities and avoidable suffering.

 The commission estimates more than 13 million lives could be saved every year if mental illness was treated properly—or at all. Alongside the profound costs of human lives and avoidable suffering, there are colossal financial ramifications. Indeed, epidemiological modelling suggests the rising cost of mental illness will hit $16 trillion USD by 2030.

 COVID-19 has amplified many of these issues, triggering social and physical distancing, economic hardship, and challenges in accessing care. 

The 21st century will be largely defined by our collective response to the global mental health crisis—and beacons of hope are beginning to emerge. Stigma is reducing, awareness is increasing, allowing people to slowly overcome back the barriers to seeking care. Meanwhile, venture capital funding for mental health start-ups has been growing rapidly and accelerated even more during COVID. 

 showed 146 deals ranked in nearly $1.6 billion in venture capital investments as of December 10th, 2020.

 A decade ago, there were only 3 deals, worth $6.6 million, whereas last year the total was $893 million from 111 deals. However, these advances on their own will not be able to solve the above stated global challenges. A paradigm shift is needed to solve the unprecedented complexities and challenges associated with the current global mental health crisis. This shift will require the education of governments and healthcare systems of the world, empowerment of consumers to take charge of their own mental health, and the use of technology both for prevention and treatment of mental disorders.

Convergence Mental Health as a Mechanism for Serendipity

Mental health is a prototypical wicked problem in that it embodies large numbers of diverse factors from biology, sociology, genetics, and psychology to economics and beyond.

 can counteract those influences and ease the anxiety that comes with the inherent unpredictability of the world. This outlook centers on being the agent of one’s own good luck. An individual can shift from a passive victim of circumstance to an active creator of opportunities by embracing the uncertainty that happens each day.

 Training the serendipity muscle in turn trains one’s ability to solve problems by identifying positive outcomes from situations and making accidents more meaningful. 

Interdisciplinary collaboration is the driver of serendipity. Those who operate with a serendipity mindset are not luckier than others, but rather cultivate luck and solutions by consistently seeking out new experiences and reaching across multiple industries. Convergence science is “an approach to problem solving that cuts across disciplinary boundaries. It integrates knowledge, tools, and thought strategies from various fields for tackling challenges that exist at the interfaces of multiple fields.”

 It can be a mechanism for serendipity through integration of knowledge, tools, and thought-strategies from various fields for tackling challenges that exist at the interface of multiple disciplines.

In the context of mental health, convergence science involves the integration of scientists, clinicians, bioinformaticists, global health experts, social scientists, health economists, engineers, technology entrepreneurs, medical educators, caregivers, and patients—we call this Convergence Mental Health.

 Synergy between government, academia, and industry is also vital. Convergence science is the Ariadne thread necessary to navigate the intricate labyrinth of global mental health problems, bringing about urgently needed progress in science and society. Examples of Convergence Mental Health-associated advances are outlined in the 

Table. Convergence Mental Health-Associated Advances

Innovations at all different levels are urgently needed. Solutions will need sociologists, psychologists, philosophers, ethicists, scientists, media practitioners, crisis management experts, policy makers, senior civil servants, and more. 

 provides direction for these shifts in how teams work. As COVID-19 has demonstrated, distance does not stop the wheel of innovation, and in fact can propel it by lowering the perceived barriers to novel ways of working and collaborating. As we embark on building the new normal, Convergence Mental Health will play a key role in this rapidly unfolding change.

 provides a historic opportunity to lead to a new era of innovation and progress, leading to improved outcomes for all people and preparing psychiatry to meet the unprecedented mental health challenges of the 21st century. By adopting a serendipity mindset, we can learn to harness uncertainty to create unique solutions across industries.

is Director of Innovation at a major mental health association and expert in residence at Georgetown University, and the author of

 is a masters candidate in Global Affairs from New York University. 

is Senior Advisor to the OECD Secretary General and Head of the New Approaches to Economic Challenges Unit at the OECD.

professor of psychiatry at the Institute for Mental and Physical Health and Clinical Translation (IMPACT) at Deakin University.

cofounder of the PRODEO Institute, adjunct associate professor with IMPACT at Deakin University, and co-lead of the OECD Neuroscience-inspired Policy Initiative.

The World Health Report 2001: Mental health: new understanding, new hope

2. Bosely S. World in mental health crisis of ‘monumental suffering’, say experts

https://www.theguardian.com/society/2018/oct/09/world-mental-health-crisis-monumental-suffering-say-experts

3. Patel V, Saxena S, Lund C, et al. The Lancet Commission on global mental health and sustainable development.

4. Lee JL. Mental health tech startups fetch record investments with COVID-19. 

https://www.reuters.com/article/health-coronavirus-mental-health/mental-health-tech-startups-fetch-record-investments-with-covid-19-idUKKBN28P1SA

Convergence: Facilitating Transdisciplinary Integration of Life Sciences, Physical Sciences, Engineering, and Beyond

7. Eyre HA, Berk M, Lavretsky H, Reynolds C. 

8. Eyre HA, Lavretsky H, Forbes M, et al. Convergence science arrives: how does it relate to psychiatry? 

10. Richardson S, Sinha A, Vahia I, et al. Brain health living labs. 

Why mental health matters to global health.

12. Shah RN, Berry OO. The rise of venture capital investing in mental health. 

13. Chang DD, Storch EA, Black L, et al. Promoting tech transfer between space and global mental health. 

14. Ternes K, Iyengar V, Lavretsky H, et al. Brain health INnovation Diplomacy: a model binding diverse disciplines to manage the promise and perils of technological innovation. 

15. Smith E, Ali D, Wilkerson B, et al. A Brain Capital Grand Strategy: toward economic reimagination. Mol Psychiatry. 2021;26(1):3-22.

16. New Approaches to Economic Challenges, PRODEO Institute. Neuroscience-inspired Policy Initiative. Organisation for Economic Co-operation and Development. Accessed March 23, 2021. 

This mindset might be the key to mental health breakthroughs. 

Feeling Lucky? Convergence Mental Health as a Mechanism for Serendipitous Innovation

Decades of research have investigated inflammation and mental illness, suggesting that there is a robust and complex link. However, the link lacks diagnostic specificity and varies considerably among individuals, and with each stage of illness. Chronic, low-grade 

appears to precede the initial illness episode, at least in some individuals.

 Drugs that modulate the immune system may also affect an individual’s mood and have possible psychiatric adverse effects (AEs). Perhaps the best example is that interferon-α treatment of hepatitis C precipitates depressive episodes.

 is associated with reduction in inflammatory markers.

Statins are best known as competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Statin treatment results in lower low-density lipoprotein cholesterol levels and in benefits to cardiovascular health. Statins also have anti-inflammatory mechanisms of action, including T-cell downregulation, suppression of cytokines, production of chemokines and C-reactive protein, and downregulation of transcription factors.3 In a post hoc, pooled analysis (N = 969) of data collected at baseline and at a 1-year follow-up from a study of patients with acute coronary syndrome, statin treatment was shown to reduce levels of interleukin (IL)-6 and IL-18. Raised levels of these cytokines appeared to predict depression after acute coronary syndrome.

Many epidemiological studies have shown that 

 is associated with a lower risk for depression (

 A population cohort study (N = 4,607,990) using Swedish national registry data investigated the relationship between statin use and the development of depression. The use of any statin was associated with an 8% decrease in risk for depression (odds ratio [OR], 0.92) compared with individuals who did not use statins.

 Elsewhere, in a cohort of individuals 55 years and older (N = 2804), statin use was associated with decreased depression (OR, 0.71).

 However, no association between statin use and depression was determined in an analysis of data from 19,114 individuals, most of whom were 70 years and older, of whom 5987 used statins.

Evidence from clinical trials suggests that, adjuvant to treatment with antidepressants, some statins are associated with better treatment outcomes. A 

 showed that treatment with lovastatin, atorvastatin, and simvastatin, adjunctive to antidepressant treatment, was superior to treatment with a placebo adjunctive to antidepressant treatment for improving depression (indexed by the Hamilton Depression Rating Scale).

 More recently, the results of a trial of rosuvastatin for young individuals with depression indicated that rosuvastatin failed to beat the placebo on the primary outcome, but it was positive on a number of secondary outcome measures, leaving the benefit uncertain.

A trial comparing simvastatin (n = 33) with placebo (n = 33) in participants with schizophrenia treated with risperidone found significantly higher reduction in the first group in negative symptom scores (P = .003) and total score (P = .001). These results measured the time period from baseline to week 8, using the Positive and Negative Syndrome Scale (PANSS).

 Simvastatin did not significantly differ from placebo for treating schizophrenia in an underpowered study (N = 36).

Two meta-analyses of statin add-on therapy in the antipsychotic treatment of schizophrenia have been conducted. 

 identified 5 randomized controlled trials (N = 236) showing improvement of PANSS total score, but not of PANSS subscale scores.

 The meta-analysis included studies of atorvastatin, lovastatin, pravastatin, and simvastatin. Risperidone was used in 3 studies; antipsychotic use was varied or not reported for 2 studies. 

 identified 6 randomized controlled trials (N = 339) showing benefit for improvement of PANSS positive and negative subscales.

 The meta-analysis by Shen et al included all 5 trials from the Nomura et al meta-analysis plus an additional trial of simvastatin versus placebo.

 have been associated with an increased risk for cardiovascular disease (CVD), independent of psychotropic medication use. This comorbidity is bidirectional, since depression is a common outcome after myocardial infarction and is also associated with higher comorbidity and mortality.

 In this context, treatment with statins may have an important dual purpose, with benefits to both mental and cardiovascular health. Evidence from a nested case-control study has shown that exposure to statins and aspirin is associated with a reduced risk of de novo major depression.

Atorvastatin, lovastatin, and simvastatin are lipophilic, while pravastatin, rosuvastatin, pitavastatin, and fluvastatin are hydrophilic. The lipophilic statins readily cross the blood-brain barrier. Hydrophilic statins or their active metabolites may also be detected in the brain, although less readily. Laboratory studies have suggested that statins may be neuroprotective against a range of neurotoxic insults, but statins themselves may be neurotoxic at higher concentrations than those obtained at therapeutic doses.

The best evidence that statins reduce markers of inflammation is derived from the JUPITER study of rosuvastatin.

 It is unclear whether brain penetrance or reduction in peripheral markers of inflammation is the more important mechanism in terms of potential therapeutic efficacy.

There is a potential for drug-drug interactions between statins and psychotropic agents (

). Psychotropic agents with lower cytochrome P450 (CYP450)activity should be considered ahead of those with known strong CYP450 activity to reduce the risk of pharmacokinetic drug-drug interactions.

 Andrade suggests that risks of pharmacokinetic drug-drug interactions between selective serotonin reuptake inhibitors (SSRIs) and statins are negligible at standard therapeutic doses for escitalopram, citalopram, and paroxetine with rosuvastatin, pitavastatin, and pravastatin; there is possible but low risk of interactions for combinations of fluvoxamine with atorvastatin, simvastatin, or lovastatin.

 A study of blood specimens collected from elderly patients (N = 194) investigated the interactions between statins and antiepileptic drugs, including the mood stabilizers lamotrigine and carbamazepine. Carbamazepine, but not lamotrigine, significantly interfered with 

, with lipids reduced for patients taking either drug but significantly greater reduction in lipids for those taking 

 Risks of adverse events may be greater in elderly cohorts compared to nonelderly individuals.

Antipsychotics may upregulate gene expression of lipid metabolism pathways, resulting in metabolic side effects, weight gain, and dyslipidemia. Individuals receiving antipsychotics may have reduced response to treatment with statins for dyslipidemia, with a common gene variant (SREBF1) for a transcription factor in the lipid metabolism pathway.

Preliminary studies suggest that adjuvant treatment with a statin may be beneficial for patients who are also prescribed psychotropic drugs for depression and schizophrenia.

Michael Berk, MD, PhD

Articles

Boosting Brain Health After COVID-19: A Convergence Solution

Feeling Lucky? Convergence Mental Health as a Mechanism for Serendipitous Innovation

The Psychiatric Potential of Statins

Exploring N-Acetylcysteine in Psychiatry

Convergence Mental Health: A New Pathway for Transdisciplinary Innovation and Entrepreneurship