UCLA Receives $22.5 Million to Explore the Fundamental Biology of Mental Disorders

The National Institutes of Health has awarded $22.5 million to a team of scientists centered at the Semel Institute for Neuroscience and Human Behavior at UCLA to fund the Consortium for Neuropsychiatric Phenomics (CNP), an interdisciplinary, campuswide effort to understand the biology underlying a variety of mental disorders.

Phenomics is the study of an organism's full complement of phenotypes - those manifest characteristics, ranging from single proteins to anatomical traits and complex behaviors, that result from the organism's genetic makeup and environment, said Robert Bilder, UCLA professor of psychiatry and director of the new consortium. Understanding an organism's phenotype is the next logical step following the recent decoding the human genome. That decoding effort, which discerned the DNA sequences that form the basic instructions for biological processes, was designed to enable the identification of genetic variations responsible for the major diseases that plague humankind.Phenomics takes a more holistic viewpoint, Bilder said. To understand how these genetic variations are associated with disease now requires the decoding of the human phenome, the sum of the physical and behavioral manifestations of those genetic variations and how they interact with the environment.Understanding the fundamental biological bases of neuropsychiatric disease - from the molecule to the mind - is an enormous challenge and will offer a grand challenge to biomedical research for the rest of the century, he said.

Currently, psychiatrists do not possess the types of laboratory tests or biological models that can be useful in studying these disorders, Bilder said. The diagnostic systems we have in place are widely acknowledged to be flawed, because the phenotypes we have are not based on research but are descriptive, he said. That is, they are based on symptoms we usually learned about, ironically, from asking patients who have disorders that make communication difficult.We so far lack markers to identify more fundamental deficits, he said. We need to drill down and get closer to the specific level where a gene might be responsible for the process. That is the goal of the consortium, which will target the behavioral and cognitive functions thought to underlie such neuropsychiatric syndromes as schizophrenia, bipolar disorder and attention deficit hyperactivity disorder. In a departure from science-as-usual, the consortium will aim to discover the underpinnings of basic, healthy functioning systems - such as memory and impulse control - rather than concentrating on the genetic anomalies that may be associated with the neuropsychiatric disorders themselves. By focusing on these healthy brain systems, the researchers hope to accelerate the discovery of genes that are relevant to mental disorders and to find new treatments.

Employing a broad approach to attacking this problem, the consortium team comprises 52 investigators, many affiliated with the Semel Institute but cutting widely across campus disciplines as well, with members from the fields of psychiatry, neurology, neurobiology, human genetics, psychology and computer science collaborating and sharing data. Subawards will support research in Finland (at the universities of Helsinki and Oulu), at the University of California, Santa Barbara, and at the Medical University of South Carolina. This interdisciplinary approach is a major goal of the consortium, which is one of nine nationwide being funded by the NIH's Roadmap for Medical Research program. The Roadmap program is designed not only to address health challenges that have been resistant to traditional research approaches but to fundamentally change how research is conducted, by integrating a wide range of disciplines to attack a problem. As opposed to multidisciplinary research, which involves teams of scientists approaching a problem from within their own disciplines, interdisciplinary research integrates elements from a wide range of disciplines, often including basic and clinical research, behavioral biology, and social sciences, so that all of the scientists may approach the problem in a new way.

The interdisciplinary research programs within the Roadmap embody a central goal of this program - to help transform the way research is conducted, said Dr. Elias A. Zerhouni, NIH director. These programs are designed to encourage and enable change in academic research culture to make interdisciplinary research easier to conduct for scientists who wish to collaborate in unconventional ways.Our team is thrilled to have this opportunity to forge a unique path in neuropsychiatry research, Bilder said. Many scientists and clinicians already acknowledge major limitations in the current system for diagnosing and treating patients. We believe the CNP strategy strongly complements existing approaches and offers new hope for discovery.For more information about the consortium, visit www.phenomics.ucla.edu.