For 25 years, Akira Sawa, M.D. has worked at Johns Hopkins University at the intersection of psychiatry and neuroscience, and focuses his research on severe mental illnesses and their neurological sources. He is Professor of Psychiatry and Behavioral Sciences, Director, Johns Hopkins Schizophrenia Center, Professor of Genetic Medicine, Professor of Pharmacology and Molecular Sciences, Professor of Biomedical Engineering and Professor of Neuroscience.
What brought you to Johns Hopkins University?
I began my career as a clinical psychiatrist in the 1990s, before coming to Johns Hopkins. As a clinician, I quickly realized the critical importance of having a scientific understanding of mental illnesses. Without the solid “medical” research for mental illnesses, people who lived with the diseases were always suffering from major social stigma. To overcome this dilemma, I looked for a place where I would be able start my “real” professional career. In the late 1990s, only small number of psychiatrists were running the top neuroscience laboratories. However, Professor Solomon H. Snyder, M.D. at Johns Hopkins was not only one of them, but the best of them. Thus, I am very lucky that I was accepted by Professor Snyder as a fellow to start learning research.
How and why did you choose your research subject matter?
I was always interested in what might be innovative. When I was a medical student, I was interested in organ transplantation, but I was also on the ski racing team, and was more of an athlete than a scientist. I admired what the transplant surgeons were doing and saw it as very decisive, and very efficient. I once decided to go into surgery, with the hope of doing something very innovative. In 1989, I was a summer student in Cambridge, England, and was able to watch liver transplant surgeries by a Lasker Award winner.
I visited more than one leading institute with expertise in organ transplantation at that time, and was a bit shocked by how all organ transplants seemed to be successful. I soon learned that it was because of the development of a method to avoid tissue rejection. I originally thought that if I spent the summer watching organ transplantation, I could watch a miracle happen. Instead, what I discovered was the importance of the research into immunosuppressants, which are the key to the success of these transplant surgeries.
Consequently, I lost interest in trying to become a surgeon because I thought I could develop a miracle hand in surgery. But it was not to be. What appealed to me most was the research stemming from clinical medicine. This was in the 1990’s, and I began to think about what areas of medicine needed the most innovation. Which discipline was the most underdeveloped? Unfortunately, it seemed to be psychiatry, which led me to follow this path. I thought that if I went into psychiatry, I could contribute to its daily practice through medical research and scientific innovation.
When I started caring for patients, treatment in psychiatry was very limited, and there was a crippling stigma associated with mental illness. Working as a doctor, I saw patients suffering from losing their job, or the ability to interact in society because of psychiatric problems. This further emphasized the potential science could have to help them. I could see that research would be the driving force to develop new treatments, as well as minimizing the stigma.
What are the biggest challenges for you, then and now?
The biggest challenge was a process related to transferring my medical license to this country. However, in addition to the extraordinary kindness of Snyder, who really helped me come to Hopkins from my very first contact with him, I had tremendous support from two more of my senior colleagues and mentors here at Johns Hopkins:Paul Rothman, M.D. and Raymond DePaulo, M.D.. They opened doors for me and paved the way for me to pursue my career, and they minimized the challenges for a foreign doctor to become accredited in the U.S. Even if one does not follow the path to become a master clinician, clinical credentials are very important — for any physician-scientist. Currently I am a committee member of the American Psychiatric Association (APA), connecting patient care with research.
As director of the Johns Hopkins Schizophrenia Center, the focus of my research is adult-onset severe mental illness, including schizophrenia, bipolar disorder and major depressive disorders, and their interconnectivity. Meanwhile, the etiology and pathology of individual patients within each disease are substantially heterogeneous. The traditional categorical approach, in which each disease is studied as its own separate disorder, is insufficient. These disorders are more biologically defined along a spectrum, so that those suffering can benefit from a cross-disease or transdiagnostic approach.
For example, a recent paper from us in Nature Mental Health focuses on postpartum depression. This research topic stemmed originally from our research, published in Science in 2013, on psychotic depression and schizophrenia. These studies revealed that the same mechanism can be applied to a specific subset of patients with postpartum depression. This is an example of how the cross-disease, trans-diagnostic approach for severe mental illness — precision medicine in psychiatry — is a powerful driver of effective research.
Most adult-onset disorders are the result of an aberrant/abnormal tuning of neural network formation in adolescence. Recent research in neuroscience has proven that dynamic neural changes happen in adolescence. When young people encounter adverse and challenging life events, possibly combined with genetic factors, this can trigger adult-onset mental disorders after puberty. Thus, the years between 10 and 18 are crucial for adult-onset severe mental illnesses.
One scientific question still outstanding is why an insult or upsetting event at birth, or experiences in childhood, does not emerge as a mental illness immediately, but can often surface later, after puberty. We still do not know the exact reasons, but adolescent brain maturation is very important in explaining the knowledge gap. We look for specific molecular mediators that are elicited by the aberrant brain maturation and have an impact on adult-onset severe mental illnesses. These mediators are likely targets of drug discovery that could interfere with the process of disease onset, even prior to the onset. This is the first focus of our research.
The second focus is the devastating consequences of symptomatic re-exacerbation after onset, which we call relapse. Relapse (usually more than once) happens in many patients after onset, with multiple causes, but commonly leads to the worsening of a person’s ability to function. In summary, we study two critical features of severe mental illnesses: a neurodevelopmental element in which aberrant adolescent maturation plays a key role, and a neuro-progressive element that underlies a relapse. Both are important targets for intervention.
What do you hope to achieve in the next 10 years?
I have two dreams that may be interconnected. First, as a psychiatrist, I wish to identify several truly useful biomarkers in early-stage patients and at-risk subjects, driven from a mechanistic understanding of adult-onset severe mental illnesses. We are also collaborating with multiple entities on new biomarker measurement and novel drug discovery/development. Second, as a neuroscientist, I’m very interested in how our senses, particularly our sense of smell, may shape and influence our emotions and cognition. This topic has recently turned out to be very important because of COVID. Patients with long COVID who have long-term olfactory pathology also seem to experience emotional conditions and cognitive impairments. This topic is more neuroscience oriented, but also includes significant clinical implications.
More information on Sawa and his research: