Gene Research on Mental Disorders



A gene, or possibly two, that could  contribute to as many as one in four cases of manic depression may be on a  region of chromosome 18, according to a study of 395 members of
22 families by Wade H. Berrettini and colleagues at Thomas Jefferson University in Philadelphia.

Manic depression or recurrent depression afflicted 167 participants in the study; in eight of the families, similar genetic variations on chromosome 18 were identified. Although this means almost two-thirds of the families had no evidence of involvement by chromosome 18, that alone would not rule out the locations: Most scientists seeking the genetic basis of manic-depressive illness agree that more than one genetic miscue probably can set the state for, or cause, the disorder.

The study, reported in the Proceedings of the National Academy of Sciences (June 21), noted two genes worthy of suspicion out of the approximately 100 genes on chromosome 18. One codes for a protein that plays a specific part in chemical signal reception; the other is involved in stress hormone production, a physiological function that has been shown to go into overdrive in both depression and manic depression.

–Reprinted from Brain Work: The Neuroscience Newsletter


According to a recent study at the Duke University Medical Center, some cases of autism may be associated with a family history of depressive illness. Autism, a disorder marked by social withdrawal and an inability to interact with the environment, seems to appear more frequently in families with a strong history of bipolar illness, the study found.

In connection with his study of 40 autistic children, Duke researcher Dr.Robert DeLong reported in the journal Developmental Medicine and Child Neurology that in 14 of the cases reviewed there was a strong family history of depression or manic depressive illness.

The study hypothesized that when manic depression strikes in early infancy, it may blunt the child’s cognitive, social, and emotional development irreversibly, so that the child’s brain never develops the framework in which to build communications skills. In extreme cases, this may lead to clinical autism.
(Reprinted from the National DMDA Newsletter, vol. 7, no. 1)


The Office of Technology Assessment  (OTA) recently published a background paper, Mental Disorders and Genetics: Bridging the Gap Between Research and Society, that reflects discussion at a 1993 workshop cosponsored by OTA and NIMH. The paper updates research on the genetics of selected mental disorders and considers the implications of these studies for future research, clinical practice, and society at large.

Research makes clear that genetic factors contribute to many of the severe mental disorders discussed in the report. “Indeed, researchers have already located, and in some cases identified, specific genes involved in Alzheimer’s disease. The consistent evidence for a genetic contribution to schizophrenia and major mood disorders, together with the rapid advances in molecular genetics, makes continued research in this area a  promising endeavor.

But progress is likely to be slow, given the complexity of theses conditions,” write the authors. Workshop testimony also made clear that genetic research carries with it clinical, ethics, and social  implications. People with mental disorders and their families worry about the genetic risk for a serious  mental disorder that their family members may face.

They welcome the de-stigmatizing influence of this research. Yet they fear its potential abuse. Unfortunately, a gap separates scientifically based information from the people who need it: people with mental disorders, their family members, care providers, and society in general. Copies of the 64-page paper are available for $4.25 through the Government Printing Office bookstores (202/512-1800). The stock number is 052-003-01392-4


Wolfram syndrome is a rare inherited disorder that leads to an array of symptoms, including diabetes mellitus and blindness. More important, the syndrome’s victims usually suffer from
severe nervous system abnormalities that can be accompanied by behavior problems, psychiatric hospitalizations and–in 25 percent of cases–suicide attempts.

Now scientists at the National Center for Human Genome Research’s Laboratory of Genetic Disease Research and the New York Medical College have used a kind of genetic assessment called linkage analysis to home in on the likely location of the Wolfram gene: the short arm of chromosome 4.

Wolfram syndrome is an autosomal recessive disorder, which means that to be affected, an individual must inherit two mutated genes, one from each parent. Between one in 50,000 to 100,000 people in this country inherit Wolfram syndrome.

Although the syndrome itself is rare, experts estimate that about 1 in 100–or as many as 2.5 million Americans–possess a single copy of the mutated gene. Because these individuals, as well as close relatives of people with Wolfram syndrome, experience higher-than-normal rates of psychiatric illness, eventual isolation of the gene may shed light on the contribution of genes to psychiatric disorders.

Armed with that information, investigators hope to identify the function of a gene that, they note, “may be responsible for a significant proportion of psychiatric illness in the general population.” Senior author of the Wolfram gene study was Mihael H. Polymeropoulos of the Laboratory of Genetic Research at the Division of Intramural Research. It was published in the September 1994 issue of Nature Genetics.


Studies by scientists at The Johns Hopkins Medical Institutions suggest that the brain uses a common chemical to adjust the speed and intensity of the messages carried through its circuits. Researchers showed that adding a phosphate molecule to brain cells can make it easier for messages to go through. The demonstration provides  important insight into the tools the brain uses to create learning and memory.  The same tools may also play a role in brain damage from strokes and other disorders.

Richard Huganir, Ph.D., associate professor of neuroscience and an associate investigator at Howard Hughes Molecular Genetics Institute, studied phosphate molecules’ effects on certain receptors, sites on nerve cells that open in response to chemical messengers from other nerve cells.

While the receptors are open, calcium and sodium from around the nerve cell flow into it, triggering a series of electrical and chemical chain-reactions that transmit the message up the nerve cell. “A single receptor that we studied probably has 10 to 20 different sites where this phosphate molecule can be added, and each of these sites has different effects on the receptor,”  explains Huganir. “

At one site, phosphorylation increases the amount of time the receptor is open,” says Huganir. “Another affects the concentration of receptors, causing more to gather in a particular area.” When a receptor is open longer or more receptors are gathered together, more of the calcium surrounding the cell flows into it, making the message come through more easily and more strongly. Huganir presented his findings at the annual meeting of the Society for Neuroscience in November in Miami Beach.


In the largest study to date using linkage analysis for bipolar, researchers at New York State Psychiatric Institute, part of columbia-Presbyterian Medical Center in New York, andthe Hadassah-Hebrew University Medical Center in Jerusalem have found evidence that a region on chromosome 21 contains a gene for the disorder.

The study involved more than 900 people from 47 families in the U.S. and  Israel with a high concentration of bipolar disorder. One U.S. family consisting of 67 individuals included 18 members who had diagnoses ranging from bipolar disorder to recurrent major depression to cyclothymia. The researchers found that DNA markers from region q22.3 of chromosome 21 gave evidence of linkage to the disorder in this family and, possibly, in other families as well.

The study comes on the heels of other recent findings showing a possible site on chromosome 18, which may also be partly responsible for manic-depressive symptoms. Still earlier studies have shown a possible relation between chromosome 11 and bipolar illness.
(Reprinted from the National DMDA Newsletter, vol. 7, no. 1)


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