The disability-adjusted life year (DALY) is a measure of the overall burden of disease, expressed as the number of years lost due to ill-health, disability, or early death. In Japan, disorders such as depression, dementia, and schizophrenia are the most common mental illnesses. Furthermore, the WHO predicts that depression will become the number one health burden globally in 2030, ahead of heart disease and traffic accidents.

“The DALY index shows that mental illness has a very damaging effect on the daily lives of sufferers. Mental illness and mental health disorders are now extremely important issues for people all over the world, not only in Japan. We live in an age where the question is no longer how to live a long life, but how to live a long life in robust health.”

In recent years, the world's perspective of mental illness and mental health has changed.
“Not so long ago, mental illness and mental health treatment were viewed with great prejudice, but recently, concern for mental health and psychological wellbeing has become much more prevalent. Here at the Department of Neuropsychiatry, we are committed to unraveling the mysteries of the mind and brain and contributing to solutions for a variety of issues.”

Professor Mimura says that psychiatry is undergoing a major change. But what is changing, and how? Professor Mimura explains this transformation from his perspective as an expert in cognitive neuropsychology.

“Psychiatry encompasses various fields such as psychopharmacology, psychopathology, and cognitive neuropsychology, all of which are concerned with hypothesizing and testing the relationship between the brain and the mind, or the brain and behavior. Cognitive neuropsychology was originally concerned with researching functional localization of the brain to determine how damage to certain areas affects psychology and behavior. For example, damage to the hippocampus will impair memory, and damage to the frontal lobe will impair judgment and problem-solving abilities. ”

Traditionally, this field has developed through basic research using animals as well as clinical observation of patients.
“A well-known example is Phineas Gage, a nineteenth-century American patient who suffered a blasting accident in which a thick iron bar pierced his frontal lobe, causing him to develop behavioral abnormalities years later. In this way, knowledge in the field of cognitive neuropsychology was acquired by studying and analyzing people whose behavior had been altered after head trauma or who had suffered from diseases such as stroke. ”

Later, researchers developed methods for objectively assessing clinical symptoms. However, the pathological mechanisms were not fully elucidated, and these methods were sometimes criticized as having no scientific basis. Beginning in the 1990s, however, the methodology of the field developed by leaps and bounds.

“With the development of imaging techniques such as MRI, SPECT cerebral blood flow imaging, and PET scanning, it is now possible to look at the functions and structures of the brain and their relationships to psychological phenomena in living patients rather than at autopsy. These technologies have greatly expanded the scope of neuropsychological research to include not only localized brain damage but also all manner of psychiatric disorders including dementia, as well as the brain function of healthy people. ”

We are moving toward an age in which we can visualize the structure and function of the living brain. Thanks to innovations in research methods, the Department of Neuropsychiatry at Keio University School of Medicine has already achieved results that have led to the elucidation of the underlying pathologies of various disorders.

In 2016, in collaboration with Japan’s National Institutes for Quantum Science and Technology, researchers from the department discovered abnormalities in neurotransmission functions related to depression.
“It had previously been suggested that noradrenaline played a role in causing depression, but it was not exactly clear what changes took place in the patient's brain. As a result of PET scan measurements using drugs that bind to noradrenaline transporters (NATs) in the brain, we found that NAT density in the thalamus was greater in depressed patients, which correlated with greater attention and arousal functions. We expect that this discovery will lead to more effective selection of antidepressants and the development of new drugs to treat depression in the future. ”

In 2020, through joint research with Yokohama City University and other institutions, the department succeeded in visualizing AMPA receptors in living brains. AMPA receptors support the functioning of the brain.
“AMPA, which plays a crucial role in neurotransmission in the brain, had previously not been visualized in a living brain. In the future, we will be able to dramatically improve the development of diagnostic and therapeutic methods by understanding the characteristics of AMPA changes in the brain using PET imaging of AMPA receptors in patients suffering from disorders such as schizophrenia, depression, bipolar disorder, dementia, epilepsy, and addiction.”

That same year, in collaboration with the National Institutes for Quantum Science and Technology, the department succeeded in visualizing an abnormal protein that may cause geriatric depression.
"Depression and delusional disorder in old age have generally been regarded as intrinsic, or of unknown cause, so to speak. In this study, we found an accumulation of tau protein in the brains of some patients with geriatric depression, indicating that it may be a factor in such mental disorders. Going forward, we expect to develop objective diagnoses and therapeutic agents using tau accumulation as an indicator.”

The department has also produced many other promising research findings, such as studies that measure amyloid accumulation in the brains of Alzheimer's patients using blood and MRI scans and identifying areas of the brain that cause motivation disorders.
“The decade since 2010 has been called ‘A decade for psychiatric disorders,’ and great expectations have been placed on us to fully elucidate these disorders. As of 2021, however, we unfortunately do not yet have the full picture, but I am certain that we are making great progress. ”

While diagnostic imaging and analysis are evolving, some things remain unchanged in clinical practice.

“If there are ten patients with depression, each of their conditions will be different. It is critical to observe the patient in front of you, listen to their complaints, and think about how to treat them. This ‘symptom-based psychiatric care’ is the foundation of all psychiatry, and we will continue to honor this approach going forward.”

One of the strengths of Keio's Department of Neuropsychiatry is that it preserves these traditional methods while also utilizing cutting-edge techniques.
“We are already preparing to implement a number of new technologies in clinical practice, including an image analysis system that enables the early diagnosis of depression and bipolar disorder, which are usually difficult to diagnose, and a verbal AI medical device that assists in the diagnosis of dementia from a 10-minute conversation.”

The Department of Neuropsychiatry has developed through a fusion of tradition and innovation as well as collaborations between basic and clinical science.
“In our department, many laboratories utilize different methods, but we all have the same goal in mind. This goal is to elucidate phenomena of the brain and mind and provide diagnosis, treatment, and preventive techniques based on scientific evidence. For this reason, members of the department often participate in intra-departmental research groups that bring different laboratories together to discuss ideas with one another. It's as if each laboratory is taking a different route to reach the top of the same mountain.”

Keio University Hospital is currently working on a project that will see the full-scale implementation of AI (artificial intelligence) in all its departments, including the Department of Neuropsychiatry. The project was selected by Japan’s Cabinet Office for its Innovative AI Hospital System (AI Hospital) Project as part of the Cross-ministerial Strategic Innovation Promotion Program (SIP). This selection has led to the development of a variety of projects, including medical imaging and analysis and the utilization of big data in medicine.

One aspect of the project is an automated electric wheelchair driving system developed mainly by Professor Mimura and his team. This project has already been in full-scale operation since last year.
“I have always tried to alleviate the challenges that driving poses for the elderly and people with dementia. I consider it part of my life work. Elderly patients and patients with mobility difficulties have a hard time moving about the hospital. So we imagined what it would be like to have a personal mobility system that could automatically transport them, for example, from the blood sampling room to their examination room. This kind of system not only leads to the safety and security of patients but also reduces the burden on hospital staff. We have plans to further expand this system in the future.”

Another project is underway to install bed sensors that can estimate sleep depth.

“The system uses sensors attached to the legs of the bed to measure fluctuations in the patient’s heart rate and respiration to estimate sleep depth, which tells us how well a patient is sleeping. This system will be useful for understanding the condition of patients with insomnia and dementia, and for measuring the effects of medications. It may also help predict and diagnose delirium that occurs after surgery and other procedures.”

Efforts are also being made to improve the efficiency of the hospital. These include the introduction of robots that transport drugs to predetermined locations in the hospital and AI-equipped cameras that quantify crowding caused by bottlenecks and collect information to reduce congestion in the hospital.

“I hope that these proof-of-concept trials at Keio University Hospital will help hospitals and clinics all over the country and the world provide better medical services in the future.”

Professor Mimura is very busy as a researcher and clinician and puts his expertise to use in a variety of roles. These include the Japanese Society of Safe Driving and Medical Conditions, which studies issues such as the impact of cognitive and physical functioning on automobile driving, and the Research Center for Financial Gerontology, which explores economic issues arising from longevity and aging.

Based on his own experience, he advises early-career doctors and researchers to deepen their liberal arts education, regardless of their background.

“Financial gerontology, for example, is an area that is deeply connected to economics and law, and we are working with researchers from the Faculty of Science and Technology and the Faculty of Environment and Information Studies on ‘AI hospital’ projects such as automated driving systems and bed sensors. Knowledge and interest in a diverse range of fields are essential for this kind of collaboration. Also, especially in neuropsychiatry, doctors need to possess a wide range of knowledge on topics such as social events, types of thought, and philosophy to be able to deeply understand their patients as they interact with them. ”

When he was young, Professor Mimura was admitted to the University of Tokyo’s Faculty of Letters Field 3 (Language and Culture), but he instead took Keio’s entrance exam and went on to study at the Keio University School of Medicine. “As I was studying a wide range of subjects such as international relations and the philosophy of science, my interest gradually shifted to psychology, and I eventually decided to become a psychiatrist.” There are now many researchers in the Department of Neuropsychiatry who have shifted their career paths from the humanities.

The Department of Neuropsychiatry at Keio University School of Medicine celebrated its 100th anniversary in 2021. In June 2021, the department held commemorative symposiums online to discuss the last 100 and the next 100 years of Keio Medicine.

“As I look back over the past 100 years, I realize that psychiatry has been advancing at an accelerated pace over the past 20 years—and over the past 10 years in particular. In 1921, when the psychiatry department was established, it would have been impossible to even imagine the situation we’re in today, with MRI brain scans and AI processing of brain data with machine learning. Thinking ahead, I’m certain neuropsychiatry 100 years from now will be far beyond what we can imagine today. There may not even be a field of psychiatry at all, or it’s possible that every department may come to have a psychiatry-like component.”

Professor Mimura also shared what kind of developments he expects will happen over the next 100 years.

“I hope that the next generation will pursue bold research that challenges conventional wisdom. At Keio, we champion a spirit that seeks to understand people and the world through exploration without distinction between the humanities and sciences. We also have a culture that encourages professionals from a variety of backgrounds to pursue interdisciplinary collaboration with each other freely. I hope that this next generation of researchers will cherish their encounters with many different people and continue to learn a wide range of things. And as for myself, with the Keio spirit of hangaku hankyo (mutual teaching and learning between teachers and students) in mind, I would like to continue to pursue psychiatric research to help people around the world live long and happy lives.”

Masaru Mimura
Professor Mimura graduated from Keio University School of Medicine in 1984. He has worked in the Department of Neuropsychiatry at Keio University School of Medicine, the Boston University School of Medicine’s Behavioral Neurology Service, Tokyo Dental College’s Ichikawa General Hospital, and at Showa University School of Medicine. He has been a professor in the Department of Neuropsychiatry at Keio University School of Medicine since 2011. He is currently the vice director of Keio University Hospital and the director of the Keio Center for Stress Research. He serves as chairman of the Japan Society for Higher Brain Dysfunction, chairman of the Japanese Society for Mood Disorders, vice president of the Japanese Psychogeriatric Society, and this year's chairman of the Neuropsychology Association of Japan.