New Light Continues to be Thrown on Inherited Schizophrenia

By Wendy Wilson
The Medical Post, April 2, 1996

HAMILTON - Schizophrenia has long presented a puzzle to geneticists looking for a biologic marker for the disease but recent studies show progress is being made.

Dr. Anne Bassett, head of the genetic section of the schizophrenia research program at the Queen Street Mental Health Centre in Toronto has conducted genetic linkage studies for years.

Her work and that of others, clearly show schizophrenia to be an inherited disease that does not follow a classic Mendelian pattern, according to Dr. Bassett who presented a summary of her work recently at McMaster University here.

Anticipation is a genetic phenomenon defined by increasing severity or earlier age of onset of a disease across successive generations. Several disorders have been shown to clinically demonstrate anticipation, such as myotonic dystrophy, Huntington disease, and fragile X syndrome.

Other investigators had found evidence for anticipation in schizophrenia, but the studies had looked at parent-child pairs and may have been confounded by infertility.

Molecular biologists have found unstable DNA sequences, called trinucleotide repeats, which may provide a biological explanation for anticipation. In myotonic dystrophy longer trinucleotide expansions are seen in successive generations as the severity of the disease increases.

Research has shown that these sequences are transcribed and it is hypothesized that accumulating gene products are responsible for the deficits of the illness.

Dr. Bassett said she set out to look for anticipation in eight large families participating in a linkage study of familial schizophrenia. Each family displayed autosomal dominant-like inheritance patterns for schizophrenia in their pedigrees.

Two to three generations of adults could be traced in each family, and many members had remained in the same geographic area and were available to interview. All had access to the same psychiatric hospital and the hospital records had been maintained since 1866.

Data were collected from 186 family members through interviews and review of psychiatric records. An increase in the rate of schizophrenia across three successive generations was found. In the grandparent generation, no family member met the diagnostic criteria for schizophrenia or schizoaffective disorders, in the parental generation eight family members were affected, and in the index generation, 30 family members were affected.

There was no evidence to suggest that a higher hospitalization rate for mental illness across the successive generations could account for these results.

All members were evaluated on a four-point scale for mental illness. The mean severity of illness was seen to increase across the three generations. Additionally, the mean age of first hospitalization for a psychiatric disorder was much younger in the index generation when compared to the grandparent generation.

Dr. Bassett was asked whether these findings have any impact for physicians counselling families with a schizophrenic member.

"First of all, we can't at all predict who's going to develop schizophrenia, all we have is recurrent risk statistics," she said.

"For somebody who's a brother or sister of someone with schizophrenia, their risk of getting the illness is in the neighborhood of 10%-15%, and the risk to their offspring is only 2%-3%. We still don't understand the inheritance well enough to be able to be more specific in the way of genetic counselling."

Dr. Basset said, "finding anticipation, the clinical phenomenon, (in schizophrenia) gives us impetus to go out and look now for this new kind of unstable mutation which would include trinucleotide repeats. We haven't found it yet, but our group and many other groups around the world are now hot on the trail in trying to find unstable mutations."

Copyright 1996 Maclean Hunter Publishing Limited
Reprinted with permission.

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