| Source: Stanford Medicine, Department of Psychiatry and Behavioral Medicine

The theme of the 2019 World Economic Forum (WEF) in Davos, Switzerland, was "Globalization, 4:0: Shaping a New Architecture in the Age of the 'Fourth Industrial Revolution.'" The term, handily shortened to 4IR, was coined to describe the confluence of the physical, digital and biological, and how technologies in these realms are combining to alter the human experience. Think AI and Machine Learning. It's already happening with autonomous vehicles, predictive content curation, and facial recognition. In health, it's enhancing medical imaging, personal health tools, and the capability to record and process massive amounts of data to advance research and treatment. However, there is much more to come; a "world-to-be" to craft and prepare for.

Into this international meeting of the minds in snowy Switzerland stepped the team from Stanford, themselves a perfect example of 4IR expertise in operation. In their case, to treat and solve mental illness. From the Department of Psychiatry and Behavioral Sciences, Dr. Leanne Williams and Dr. Carolyn Rodriguez partnered with Dr. Ada Poon of Electrical Engineering. They made up the fifth group of Stanford scientists sent to Davos in as many years by the Wu Tsai Neurosciences Institute to highlight the interdisciplinary research in neurosciences underway at the university. The fit could not have been better.

For the first time, the WEF featured a "dedicated mental health track," as Dr. Rodriguez described it, "raising the visibility of mental health as a global challenge, and laying the foundation for supporting ongoing global mental health initiatives."

A prime time "Mental Health Matters" panel featuring Britain's Prince William, Duke of Cambridge, and New Zealand Prime Minister Jacinda Ardern set the tone. At the premier world gathering revolving around economics, this panel drew at-capacity attendance. And no wonder. The two most common mental health issues – depression and anxiety – combine as the number one disability in the world and account for an annual loss in the global economy equivalent to one trillion U.S. dollars. The cost in human suffering is even higher. Between eight hundred thousand and one million people die by suicide every year- the world's biggest silent killer, especially of the young.

CEOs and leaders of nations squeezed in alongside funding analysts and health professionals to hear the discussion. Looking around the audience, Dr. Poon knew mental illness had finally been universally recognized as a critical public health concern when she realized she was sitting next to the Queen of Belgium, rapt as the rest.

The Stanford team unveiled its groundbreaking work at the Wu Tsai-sponsored IdeasLab.

"We presented around the theme of the Dawn of Precision Psychiatry," said Dr. Williams, founding Director of the PanLab for Precision Psychiatry and Translational Neuroscience, and architect of the Stanford Center for Precision Health and Mental Wellness. "We presented complementary perspectives on how to use precise neuroscience-based measures to develop a new system for subtyping and tailoring treatments for depression, how to use neuroscience to develop rapid-acting novel interventions for anxiety, and how to harness novel bioengineering approaches to achieve precise "readouts" of important human capacities such as memory, in order to optimize them."

 

Dr. Williams explained how she uses advanced neuroimaging technology to detect the measurable biology of depression, then subtypes the disease for precise treatment. Her breakthrough in identifying specific "short circuits" underlying the disorder means the trial and error method of therapy can be replaced by targeted remedies tailored for a half dozen distinct "biotypes." Dr. Williams' research shows her approach can double the rate of patients who go into remission with the first form of treatment administered.

As big a leap forward as this is, her message in Davos was to keep the proverbial foot on the accelerator to develop a new, integrated system for mental health.

"Just think of the technologies we can harness – genomics to refine the biotypes, machine learning for innovative classifications, a fusion of biotypes with wearable sensors for scale and expansion to new interventions as they are developed. These solutions are imperative for public health and humanity. They are also an imperative for development – knowing that each new dollar invested in mental health will generate at least a four dollar return."

Dr. Carolyn Rodriguez, Director of the Translational Therapeutics Lab and Associate Chair of Stanford Medicine's Department of Psychiatry and Behavioral Sciences, shared her advances in developing a fast-acting treatment for anxiety sufferers for whom standard therapies have been ineffective. The World Health Organization reports anxiety disorders as the most common mental health conditions on the planet. However, Dr. Rodriguez says the development of medications for psychiatric illnesses falls far behind those of other diseases; for eleven new compounds being tested to treat cancer only one will be studied to address a psychiatric disorder.

Her lab has been tackling one particularly disabling condition, Obsessive Compulsive Disorder (OCD), which research shows is linked to a hyperactive brain circuit.

"Unfortunately, it can take a long lag time of two to three months to bring about major symptom relief, and complete symptom relief is not common." Hence Dr. Rodriguez's focus on a rapid-acting treatment with longer-lasting effects. Research suggesting glutamate - the main chemical messenger involved in circuit activity - may play a role in OCD led to her work with the drug ketamine, found to block glutamate docking ports. "We found that a single low dose of ketamine caused an immediate decrease - within hours - in OCD symptoms in all participants. In half, this rapid benefit lasted up to one week."

As her lab continues testing the underlying mechanisms of ketamine's fast-acting effects, it's also got next-generation drugs with fewer side effects and longer-lasting benefits under study.

Hardware plays a vital role in both research and clinical application. In partnership with Stanford experts in transcranial brain stimulation and neurosurgery, Dr. Rodriguez is examining the use of non-invasive as well as surgically implanted devices for treatment delivery, and Dr. Williams is integrating imaging technology with other sensors to individualize early detection and treatment prediction.

Here is where the work of Dr. Ada Poon, Associate Professor of Electrical Engineering and Chan-Zuckerberg Biohub Investigator, completes the 4IR triad in precision psychiatry. In her research of bioelectronic medicines – the use of electronic devices to treat illnesses - Dr. Poon discovers ways to miniaturize implantable devices so they can be seamlessly integrated with the human body. She felt a charge go through the IdeasLab when she displayed her implantable pacemaker and brain stimulator, smaller than a grain of rice.

"The audience was excited by the size of the device, and by research showing how it is remotely-controlled in mice, and in pigs because of their closeness to human scale in terms of size. Compared to pharmaceutical drugs which act globally throughout the body causing side effects, bioelectronic devices can directly communicate with the specific area of the body, acting on it immediately. Bioelectronics provides exquisite spatial and temporal resolution, and they can be easily programmed and personalized."
The marriage of electrical engineering and medicine makes perfect sense to Dr. Poon, "Our nervous system is coordinated through neural impulses which are electrical in nature; bioelectronics is speaking the language of our nervous system. We can use it to communicate with our bodies as a therapeutic treatment."

Dr. Poon is broadening her research to use micro-implants for treating other diseases currently incurable through drugs. She is developing a memory recovery micro-implant that would progressively reverse short term memory loss in Alzheimer's disease, an "electronic" pancreas to address the global shortage and skyrocketing cost of insulin, and an EEG sticker to monitor overall mental health as a preventative tool.

"What is the equivalent of diet and exercise for the body, for the brain and mind?"
It is no small feat to coordinate a team of this caliber, sending scientists six thousand miles from their labs, but the consensus of Stanford's 'Precision Psychiatry' doctors, with gratitude to Wu Tsai Neuro, is that it was well worth the trip. The message they carried to Davos was that mental illness is real, there are solutions, and the time is now to utilize innovation to scale up the response in a big way. By all accounts, it was well received. Each scientist reported new opportunities for collaboration, investment, and implementation they say would not have been possible in any other setting. With the world view the WEF provided them, they see Stanford as well-positioned to lead the future of neuroscience-based mental health solutions.

 

"I was struck by the profound and notable attention to mental health at WEF. It is a sea change for our field, and there are new opportunities for collaboration and team science opening up across nations." -- Dr. Carolyn Rodriguez

"It was rewarding, as an engineer, to share the message that there are different ways to think about solutions to big global problems like mental illness. It was inspiring to see so many concerned about mental health, and reinforced the belief in the work we are doing." -- Dr. Ada Poon

"This was a moment I had hoped I would witness in my research lifetime ... It was a rare opportunity to experience alignment of our neuroscience message with alignment of development priorities." Dr. Leanne Williams concluded, "The WEF does receive criticism that it reflects privilege without action for all. My experience on this occasion was that there is an openness and hunger for mental health solutions based in hardcore science – in our case neuroscience – and that if privilege can be used to drive real change, then that will ultimately be of benefit to our global community."