UB Husband-And-Wife Team Embarks On Search For Genes Linked to Schizophrenia

BUFFALO, N.Y. -- A husband-and-wife team of psychiatrists at the University at Buffalo has received a $2.6 million grant from the National Institute of Mental Health to conduct one of the first major population-based studies aimed at finding the gene or genes that may be linked to schizophrenia.

Carlos N. Pato, M.D., and Michele T. Pato, M.D., UB associate professors of psychiatry, are principal and co-principal investigators, respectively, on the project. They have been building the project for seven years in the Azores, a group of nine islands located off the coast of Portugal that comprise a Portuguese state and where most inhabitants are descended from a few families.

Both researchers hold adjunct appointments with the Center for Neuroscience at the University of Coimbra in Portugal, which is collaborating on the project. Also involved are James L. Kennedy, M.D., head of the neurogenetics section at Clark Institute of Psychiatry, University of Toronto, who is a co-principal investigator, and Eric Lander, Ph.D., of the Whitehead/MIT Center for Genome Research, which will perform a genome-wide scan and collaborate on all data analysis.

"Psychosis is a complex syndrome, the most common form of which is schizophrenia," Carlos Pato said. "In at least 20 percent of cases of schizophrenia, other family members are also affected with the illness, but genetics may play a role in an even greater percentage. Our study will try to determine how often the illness and a particular gene, or genes, are seen together. If we can find the gene that causes the illness and then find the product of that gene, we can begin to design more effective treatment."

About 1 percent of the world's population is afflicted with schizophrenia, a mental illness characterized by symptoms such as deterioration of personality, disordered thinking, delusions, hallucinations, paranoia or catonia. The main form of treatment is antipsychotic drugs, which must be taken regularly and continually to control symptoms.

The five-year study will be carried out in the Azores and in a population group on the Portuguese mainland. "The Azores are ideal for a genetic analysis," Pato said, "because the country is small and its population has been relatively genetically isolated, with most inhabitants descended from a few families. The Azores have a centralized health system, and all 10 psychiatrists on the islands are collaborating on the project."

The researchers will look for genetic links using a variety of approaches. "We will select genetic markers and look at how the markers behave in well families compared to a family where the illness shows up several times," Pato said. "We'll look to see if illness and genetic markers exist together, and we'll analyze genetic patterns from ill person to ill person. We'll develop a description of each suspect gene and determine how often it occurs with illness."

An important aspect of the study will be a Halpotype Relative Risk analysis. Using this approach, researchers will analyze the set of genes from a patient's parents that were not passed on to that patient, Pato said. The non-inherited set then acts as a control.

A field team is already in place in the Azores. The UB researchers travel there frequently to maintain close ties with the project. Meanwhile, they are setting up a genetics research program and laboratory at UB that ultimately will be capable of performing genetic analysis of any potentially inheritable disease, the researchers said.

M. Helena Azevedo, M.D., professor of psychiatry at the University of Coimbra, is the principal investigator for the Portuguese team, and Carlos Paz Ferreira, M.D., director of psychiatry at Psychiatric Hospital S. Miguel, Azores, is directing the field work.