The National Institute of Mental Health (NIMH) has awarded a $15.7 million grant to the UC Davis Silvio O. Conte Center, one of only 15 Conte Centers nationwide.
Psychiatric illnesses and neurodevelopmental disorders, including schizophrenia, affect 15-20 percent of the population worldwide, yet current treatments are at best only partially effective. The UC Davis Conte Center was first established in 2016 through the Center for Neuroscience to determine how maternal infection increases risk for these disorders and to identify new targets for novel treatments.
“UC Davis is in the upper echelon of translational mental health research,” said Cameron Carter, co-principal investigator of the Conte Center, the C. Bryan Cameron Presidential Chair in the Center for Neuroscience and a Distinguished Professor of psychiatry and psychology in the School of Medicine. “The establishment of a UC Davis Conte Center in 2016 was an incredible accomplishment, and to renew it in 2021 is an even bigger accomplishment.”
Building on promising findings from the initial grant, the renewal of the UC Davis Conte Center funding will allow investigators to discover biomarkers to identify at-risk pregnancies and new treatments to prevent the detrimental effects of maternal infection on brain development in offspring.
“The rates of schizophrenia and autism have dramatically increased following pandemics in the past, and we are deeply concerned about a similar impending wave of psychiatric illness following the current COVID-19 pandemic. Newly funded projects in our center will reveal approaches to mitigate disease in offspring and even to prevent it in future pregnancies,” said Kimberley McAllister, co-PI of the Conte Center, the director of the Center for Neuroscience and a professor of Neurology in the School of Medicine and the Department of Neurobiology, Physiology and Behavior in the College of Biological Sciences.
The origin of mental illness
When an expectant mother is exposed to a pathogen, such as a virus or bacterial infection, her body’s immune response can trigger neurodevelopmental changes in her offspring. The initial Conte Center grant enabled an interdisciplinary team of researchers to discover that this immune response can result in offspring with changes in brain development and behavior that show up surprisingly early after birth, and that are similar in species as disparate as mice and monkeys. In fact, the non-human primate maternal immune activation model, established by Associate Professor Melissa Bauman at the California National Primate Research Center, and the only such model in the world, provides an invaluable link between the mouse model and humans.
In humans, the corollaries of the changes in brain development and behavior seen in both mice and monkeys are typical of neurodevelopmental and psychiatric disorders like schizophrenia and autism, among others.
While the link between the maternal immune response and the occurrence of brain disorders in offspring is clear, not every pregnancy is at risk. In fact, most are resilient. The question is how to determine which pregnancies are at risk, and why.
“Because many of these diseases start very early in development, often prenatally, we are especially interested in understanding how the immune response of the mother during pregnancy alters brain health in her offspring,” McAllister said.
The addition of Professor Judy Van De Water, an immunologist, and Professor Alice Tarantal, an expert on primate development, to the renewed Conte Center will be critical to help understand and address these issues.
The future of mental health
The goal of the center’s renewal is to identify the factors and biomarkers that can help predict which pregnancies are most at risk, and which are resilient, as well as the specific brain circuits that lead to the wide range of diseases linked to maternal infection, from autism to schizophrenia. Once these mechanisms are understood, scientists may be able to create novel therapies, treatments and interventions optimized for the developmental age and sex of at-risk offspring following maternal infection, as well as approaches to prevent the effects during at-risk pregnancies.
The purpose of the NIMH’s Conte Centers program is to support interdisciplinary teams of researchers addressing high-risk, high-impact questions that will advance our understanding of mental disorders and their treatments. "The center exemplifies the best of UC Davis – interdisciplinary team science addressing significant problems in innovative ways to improve human health," said Leonard Abbeduto, the director of the UC Davis MIND Institute, and the Tsakopoulos-Vismara Endowed Chair of Psychiatry and Behavioral Sciences.
The Conte Center award recognizes the strength of interdisciplinary research at UC Davis, and its researchers together represent a diverse coalition of experts from multiple departments and centers across UC Davis, including the Center for Neuroscience, the MIND Institute, the Center for Mind and Brain, the Primate Center, the College of Biological Sciences, the School of Medicine, the College of Letters and Science, and the College of Engineering.
“The team at the UC Davis Conte Center is helping us understand the origins of significant diseases in mental health,” said Mark Winey, dean of the College of Biological Sciences. “And their research will have far-reaching impacts and provide foundational understandings for how we approach mental health.”
The Conte Center grant will provide $3 million each year for five years to fund five distinct but highly synergistic projects. Carter and McAllister will work together with a large team of elite neuroscience investigators, including the following Project and Core leaders:
- Melissa Bauman, associate director of the Conte Center, associate director of the UC Davis MIND Institute IDDRC, and professor of psychiatry and behavioral sciences, UC Davis MIND Institute
- Judy Van de Water, associate director of the UC Davis MIND Institute, deputy director of the NICHD UC Davis MIND Institute IDDRC, director of the UC Davis NIEHS Center for Children's Environmental Health, and professor of rheumatology, allergy and clinical immunology
- Daniel Geschwind, professor of neurology, and psychiatry and behavioral sciences, the Gordon and Virginia MacDonald Distinguished Professor in Human Genetics, UCLA, senior associate dean and associate vice chancellor of precision health, and director of the Center for Autism Research and Treatment
- Ana-Maria Iosif, professor of biostatistics in the department of public health sciences.
“The Conte Center’s NIMH grant renewal is a testament to the groundbreaking, interdisciplinary research that UC Davis School of Medicine and our main campus partners are conducting,” said Allison Brashear, dean of the School of Medicine. “It is truly impressive to see how UC Davis is bringing together its world-class leaders in neurology, psychiatry, behavioral health, and biological sciences, among others, to improve the health of current and future generations.”