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Manic depression linked to absent DNA.

To their surprise, researchers have found that a severe form of manic depression, usually beginning by late childhood, afflicts many people suffering from a genetic disorder known as velo-cardio-facial syndrome (VCFS). Further investigations of this formerly unsuspected connection may yield insight into genetic influences on manic depression, according to the investigators.

"This is the first reported link between these two conditions," says Demitri F. Papolos, a psychiatrist at the Albert Einstein College of Medicine of Yeshiva University in New York, who directed the new study. "The deletion of one or more genes in velo-cardio-facial syndrome may help to create a vulnerability to [manic depression]."

Primary features of VCFS consist of cleft palate, heart defects, learning disabilities, and a characteristic facial appearance that includes a long face, a large nose with a prominent tip, small ears, narrow eyes, and an emotionless expression. Robert J. Shprintzen, director of the Center for Craniofacial Disorders at Montefiore Medical Center in New York and a coauthor of the new study, defined this set of characteristics as VCFS in 1976. He estimates that it affects between 1 in 3,000 and 1 in 5,000 individuals.

Prior molecular investigations indicated that VCFS stems from the deletion of a specific segment of chromosome 22, Papolos notes. Between 25 and 30 genes, several of which have been identified, lie in that stretch of DNA.

The new study, described in the December American Journal of Psychiatry, included psychiatric evaluations and reviews of medical records for 25 people diagnosed with VCFS. Their ages ranged from 5 to 34 years.

Nearly two-thirds of the sample suffered from manic depression, also known as bipolar disorder, the researchers found. This condition typically features alternating bouts of euphoric agitation and severe depression that last several weeks or months. Some people with VCFS had appeared to be schizophrenic because of the severity of their untreated mania.

In the general U.S. population, manic depression affects about 1 in 100 people at some time in their lives and usually first emerges in young adulthood. In the VCFS sample, however, this psychiatric disorder was far more common and typically began at age 12. In many cases, it included rapid shifts between mania and depression, each state lasting only a day or two, Papolos holds.

In addition, nine participants received a diagnosis of attention deficit disorder (ADD), some with hyperactivity. Five people displayed both ADD and manic depression.

A gene known to be located in the deleted chromosome 22 region produces an enzyme that activates two chemical messengers, dopamine and norepinephrine. These substances have been implicated in manic depression, according to Papolos. He and his colleagues plan to examine deletions of this gene more extensively, both in people with VCFS and the population at large.

"For now, I consider this new report an interesting speculation," comments psychiatrist Elliot S. Gershon, chief of the clinical neurogenetics branch at the National Institute of Mental Health (NIMH) in Bethesda, Md. "We'll have to see if the results hold up in future studies."

He adds that four studies indicate that a gene located elsewhere, on chromosome 18, helps to produce manic depression in some people (SN: 7/2/94, p. 13).

The missing chromosome 22 region cited by Papolos' group may contain one or more genes that influence different mental disorders, depending on the presence of other DNA variations, Gershon suggests.
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Title Annotation:bipolar disorder
Author:Bower, Bruce
Publication:Science News
Date:Jan 4, 1997
Words:559
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