Renowned Child Psychiatrist and Molecular Geneticist to Join UCSF

Matthew State, MD, PhD, a leading child psychiatrist and internationally recognized expert on the genetics and genomics of autism, Tourette syndrome and other neurodevelopmental syndromes, was recently named to lead UCSF’s psychiatric programs.

As the new chair of the Department of Psychiatry and director of the Langley Porter Psychiatric Institute, State will play a key role in integrating psychiatry into the University’s preeminent neuroscience program. His appointment begins on March 18.

For State – a New York native – it’s a return to California, where he earned his undergraduate and medical degree from Stanford University. He completed his residency and a fellowship at UCLA, before moving to Yale in 2001 for a PhD degree in genetics and to pursue his academic career.

State is currently the Donald J. Cohen Professor of Child Psychiatry in the Department of Psychiatry and Genetics at Yale’s School of Medicine. He also is deputy chairman for research in the Department of Psychiatry and co-director of the Program on Neurogenetics at Yale.

State, whose appointment was first announced in November, took some time to answer these questions for UCSF.

Why did you decide to become a child psychiatrist?

I was interested in psychiatry as I entered medical school based both on experiences with family members and several good friends in college who suffered from serious mental illness. I did not enter residency training knowing that I was going to specialize in child psychiatry.

During my residency, I did a rotation on a child and adolescent inpatient service and left convinced that this was what I wanted to do. It was a combination of being inspired by my attending, loving the work with kids and families, the tremendous need for child psychiatrists, and my feeling that understanding development was going to be a key to better understanding the biology of serious psychiatric disorders.

How has gene discovery or genetics of Tourette syndromes and autism informed researchers in their quest for a cure?

It has been thrilling to be involved in studying the genetics of serious neurodevelopmental and neuropsychiatric disorders over the last several years. I have been working in this area since the late 1990s, and for the majority of that time, I felt that we were largely wandering in the dark. However, the field is now in the midst of a profound transition, where we finally have the tools in hand to identify risk genes and bring into focus the genetic architecture of disorders such as autism and Tourette syndrome.

As we identify multiple risk genes, this opens the door to deepening our understanding of the molecular and cellular mechanisms of disease, something that has been lacking in child psychiatry. This, in turn, is a critical first step to developing new and better therapeutics. In fact, this is the organizing theme of my lab: using gene discovery to illuminate the biology of mental illness and as a means to identify cures. 

Recent progress in the genetics and neurobiology of autism serve as a prime illustration of how this process can work. Over the last several years, progress in studying the biology of conditions that are accompanied by high rates of autism, such as fragile X syndrome, have transformed thinking about neurodevelopmental disorders. A series of recent studies have shown that it is at least theoretically possible to reverse symptoms even into adulthood, challenging long held notions that autism or intellectual disability are largely immutable after birth.

Similarly, recent results emerging from a collaboration between my lab and Joseph Gleeson’s [MD, professor of neurosciences and a Howard Hughes Medical Institute investigator] lab at UC San Diego have found a new, rare and potentially treatable form of autism and epilepsy caused by mutations in a gene regulating certain amino-acids. We are testing whether normalizing these amino acids will be helpful. If they are, this will apply to a small number of families carrying this very rare mutation, but it is an important illustration that understanding the causes of neuropsychiatric and neurodevelopmental disorders can open surprising new avenues to treatment.

What is the most important thing you would tell a parent whose child was recently diagnosed with TS or autism?

I would say that each family comes to this with its own experience, knowledge and questions. So the most important thing is to listen carefully and to try to respond to their particular concerns and fears. One of the wonderful things about child psychiatry is that we tend to have a bit more time to have these types of important conversations than other physicians in other medical specialties.

What has been the highlight of your academic career so far?

I feel extremely fortunate that there have been many. The lab has made good progress both in autism and Tourette syndrome after a long period of struggle, and this has been tremendously rewarding. For both disorders, some of our recent discoveries have pointed to novel approaches to treatment. This was a very distant goal 15 years ago when I started my lab. Seeing this come to fruition over the last several years has been truly wonderful.

Finally, I have a group of post-doctoral fellows and junior faculty in my lab that is doing absolutely stellar research. Our field is in desperate need of physician scientists and it is tremendously rewarding to see some of the next generation of leaders emerging from my group.

You've received numerous teaching awards. What teacher most influenced you?

I have been extremely fortunate to have a long list of outstanding teachers and mentors. I would say however, that two stand out in my professional life: Mark De Antonio, [MD, a professor of psychiatry who specializes in child and adolescent psychiatry at UCLA], was the attending physician on my first child and adolescent inpatient rotation. I have still never met a more gifted clinician or a more outstanding teacher. The experience inspired me to pursue child psychiatry as a career.  

At Yale, Richard Lifton, [MD, PhD, Sterling Professor of Genetics and professor of medicine; chair of the Department of Genetics at Yale and a Howard Hughes Medical Institute investigator], has been a pioneer in studying rare examples of common illnesses. I was fortunate to spend the vast majority of my PhD in his lab. From this time forward he has had a profound impact on my thinking how to approach the genetics of child psychiatric illnesses. I am certain that we would not have had the success we have had in the lab if it were not for his ongoing influence.

Why did you choose to join the faculty at UCSF?

I was attracted by the combination of exceptional science, exceptional patient care and exceptional training. I don’t believe there is any place that is doing a better job of integrating these missions at present than UCSF, and I care deeply about all three. In my case, this was particularly enticing with regard to the neurosciences, where I knew I would have the opportunity to work alongside great departments of neurology and neurosurgery and a phenomenal group of basic neuroscientists.

I also have to say that I could not be more excited about joining the Department of Psychiatry in a leadership role. The basic science of psychiatry is moving at light speed and yet there are very few places that are currently positioned to both lead in this area of research and, at the same time, to translate this knowledge into new and improved treatments. UCSF is poised to help transform science, clinical care and training in psychiatry in the next decade, and I thought it would be tremendously rewarding to participate in this effort.

UCSF values its work in the community and its long-standing public mission. What experience at the community mental health center in Connecticut will shape your work here?

I am a molecular geneticist. I love the elegance of great sets of experiments and the thrill of discovering a risk gene. I am convinced that basic science is an important path to transforming psychiatric care in the coming decade.

At the same time, I am a clinician and my work with patients at a community mental health center is tremendously rewarding and the source of my conviction that clarifying the molecular underpinnings of serious illness will never be sufficient in isolation. 

Psychiatrists cannot ignore psychological, developmental and social issues that all have a profound impact on our patients and their families. These issues are not going to be resolved at the wet bench. One of the things that make psychiatry so interesting is that our field needs to understand pathophysiology at many levels and, at the same, must address broad policy issues that impact the risks for developing psychiatric illness and influence access to care for our patients.  

Lastly, what excites you the most about the future as the nation looks toward precision medicine to create individual treatment plans for any patient, anywhere?

There are many things that excite me about this prospect. Of course, effective precision medicine in psychiatry would have to be predicated on a deeper understanding of molecular and cellular mechanisms of disease than we have at present. As I mentioned above, this type of knowledge is critical to developing improved treatments. It has ushered in far more effective therapies for everything from cancer to immunological disorders, and I believe that psychiatry is on the cusp of benefiting from these advances just as these other fields have.  

I also expect that as precision medicine becomes a reality in psychiatry it will be accompanied by decreased stigmatization. Our field’s lack of understanding about what is causing serious mental illness has left open the door to our patients and their families being blamed and ostracized. This was the situation with cancer many years ago, and just as knowledge transformed that field, I am confident that research and improved understanding will transform the public perception of serious psychiatric illness as well.