Our research has linked mental illness to vascular defects in the developing prenatal brain. Recent studies from our lab have identified a specialized endothelial cell population in the embryonic forebrain that can contribute to mental disorders. These cells directly impact surrounding brain cell development, including angiogenesis (the body's natural creation of new blood vessels). In our research, we combine genetic tools with developmental biology, cellular, molecular and behavioral approaches to characterize the fundamental mechanisms underlying the origins of mental illness. Our scientists have hopes of using blood tests to identify biomarkers that will distinguish between psychiatric categories, like depression, schizophrenia and autism. And while it's unsettling to think that our brains could literally be pre-wired to make us more susceptible to mental disorders, it's amazing knowing that our neurovascular scientists are working toward therapies that can correct the blood vessels at the point of defect, perhaps preventing the origin of mental illness.

• One in four people worldwide is affected by some type of mental illness.
• The average delay between mental health symptoms and treatment is 11 years.
• Since 1999, the suicide rate has risen 35%. It is the second leading cause of death for people aged 15-34, and 90% of these have an underlying mental illness.
• Depression is a global challenge, affecting more than 300 million people. Schizophrenia affects 23 million, and bipolar affective disorders affect 60 million.

Our team is testing innovative approaches to harness the natural potential of CNS (central nervous system) angiogenesis to find cures for mental disorders. Endothelial cells are known as the building blocks of blood vessels. Their signals organize the growth and development of surrounding brain cells. Exciting studies are in the early stages, but already our discoveries are cause for hope: we've had success using NAD+, a pro-angiogenic compound, to rescue angiogenesis and neurovascular interactions during a critical prenatal developmental window. This enabled us to permanently improve blood flow in the adult brain, which eliminated behavioral dysfunction.

Mental illness is a complex problem that touches us all. It's long been stigmatized and misunderstood. Our work is to dispel this, and to provide hope. We envision a future where the 'healing touch' of angiogenesis therapy will bring relief to patients suffering from mental disorders.

—Dr. Anju Vasudevan

Our scientists are beginning to model different psychiatric diseases using human pluripotent stem cell technology. As our research progresses, we expect to identify abnormal cellular phenotypes and altered gene expression that will unlock new complexities of underlying mental illness. This information will enable us to tailor our approaches to correct the cellular and molecular defects. So far, we've found the human forebrain endothelial cells generated in our lab to have considerable potential for intervening in the adult brain to repair and regenerate brain cells. Transplanting these embryonic forebrain endothelial cells has shown promise for neuronal migration, dispersion, and rescue of neural circuits—with significant benefits for behavioral outcome within just one month of transplantation.

In patients with mental illnesses like schizophrenia, multiple pathways in different cell types likely coexist, creating a 'perfect storm' for this disease to develop. Human pluripotent stem cell technology allows us to model the troubled brain in a dish, isolate its cell type-specific defects, and create targeted treatments.

—Dr. Anju Vasudevan

There are deep connections between mental illness and coronary heart diseases (CHD)—and evidence that one may actually lead to the other. Scientific studies have shown a higher prevalence of mental illness in CHD patients; conversely, people suffering from a mental illness seem to have an increased risk of CHD. In collaboration with HMRI's cardiovascular researchers, we are beginning a study to understand the mechanisms of the brain-heart connection that leads to mental illness—with the goal of someday developing treatments.

Up to 40% of patients with heart disease meet criteria for major depressive disorder