UB Psychiatric Geneticists Receive $4.2 Million To Search For Genetic Markers For Manic Depression

BUFFALO, N.Y. -- A husband-and-wife team of psychiatrists at the University at Buffalo has received a $4.2 million grant from the National Institutes of Health to search for a gene or genes that may be linked to bipolar disorder, commonly referred to as manic depression.

Identifying the molecular basis of such a linkage could lead to advances in diagnosis and treatment of the disorder, which affects millions of people worldwide.

The grant to Carlos N. Pato, M.D., and Michele T. Pato, M.D., associate professors of psychiatry and co-directors of the UB Laboratory of Psychiatric and Molecular Genetics, was announced today at a press conference by UB President William R. Greiner.

The Patos are conducting their research with the relatively homogeneous population of the Azores, Portuguese islands located in the North Atlantic about 1,000 miles off the coast of the Iberian Peninsula.

This same population forms the study base for their search for genetic markers for schizophrenia, a $2.6 million project also funded by the NIH, now entering its third year.

"We are delighted that professors Carlos and Michele Pato have received this grant for their ground-breaking research on the possible genetic components of bipolar disorder, a condition that affects so many people worldwide," Greiner said. "This award from such a prestigious funding source as NIH recognizes the important work being done by UB medical researchers such as the Patos.

"We wish them well in their research, which could lead to improved treatments and cures for this illness."

John Wright, M.D., dean of the UB School of Medicine and Biomedical Sciences, said this research exists on the cutting edge of the application of molecular biology to human disease.

"Although a genetic linkage has been presumed to underlie bipolar disease in many individuals, this research promises to reveal the molecular basis of that linkage, and may well lead to important diagnostic and therapeutic advances.

"In addition to these successful research endeavors, Carlos and Michelle Pato have made major contributions to undergraduate and postgraduate education during their relatively short tenure at the UB medical school," Wright noted. "We are all very proud of their accomplishments."

Carlos Pato, principal investigator on this research project and associate dean for clinical affairs in the UB medical school, said bipolar disorder affects about .7 percent of the worldwide population, with a large percentage having a possible genetic component.

"The most consistent and significant risk for developing bipolar disorder or schizophrenia is being related to a person suffering from the same illness," Pato said. "Though it is likely that nongenetic factors play an important role in the expression of these illnesses, a significant portion or risk must be genetic."

Bipolar disorder is characterized by dramatic mood swings between mania and depression. The mood swings develop and subside spontaneously and may be cyclic, with sufferers remaining manic or depressive for months.

Persons in the manic phase of the disorder can be psychotic, are easily distracted, experience exaggerated feelings of well being, exhibit inflated self-esteem and may indulge extravagantly in irrational activities. In the depressive phase, persons experience inertia, loss of self-esteem, withdrawal, sadness and may be suicidal.

Present treatments for bipolar disorder focus on managing these symptoms. The Patos said they hope that uncovering the genetic etiology of these disorders will be an important step in developing improved treatments and, possibly, specific cures.

Through a pilot study, the researchers already have identified 25 families with 84 affected members. That population will be expanded in the full-blown, five-year investigation to include 225 persons with bipolar disorder and their parents. A third study group will be composed of all other Azoreans with the disorder.

"The Azores are ideal for a genetic analysis because the islands are geographically isolated and the population has remained relatively homogeneous, with most inhabitants descended from a few families," Pato said. "In addition, the Azores have a centralized health system, and all 10 psychiatrists on the islands are collaborating on the project."

The researchers will look for hereditary pathways of the disease 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 haplotype relative risk analysis, Pato said. Using this approach, researchers will analyze the set of genes from a patient's parents that were not passed on to that patient. The non-inherited set then acts as a control.

Both researchers hold adjunct appointments with the Center for Neuroscience at the University of Coimbra in Portugal, which is collaborating on the project. The Whitehead/MIT Center for Genome Research, recognized internationally for its cutting-edge genetic technology, will perform a genome-wide scan and collaborate on all data analysis.

Carlos Pato holds an adjunct appointment in the UB Department of Pharmacology and Toxicology. In addition to their UB positions, Carlos Pato heads Kaleida Health's Division of Psychiatry, and Michelle Pato directs Kaleida's psychiatry residency program.