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The hypothesis that expanded trinucleotide repeats (TNRs) contribute to the pathogenesis
of bipolar disorder has received strong support from recent studies showing that,
on average, bipolar patients carry larger repeat sequences of the TNR motif CAG/CTG
than do controls. It has been postulated that intergenerational expansion of a TNR
may be responsible for the tendency for age of onset to become earlier in younger
generations (anticipation) observed in some bipolar pedigrees, and that length polymorphism
may account for variability in clinical phenotype. We have used the method of repeat
expansion detection to examine these predictions in a sample of 133 Caucasian DSM-III-R
bipolar I probands from the British Isles. We found no evidence to support the notion
that CAG/CTG TNR genes are major determinants of phenotypic severity or age at onset
in the population examined, and conclude that for most cases of bipolar disorder TNR
genes may operate as susceptibility genes rather than as single genes of major effect.
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References
- Diagnostic and Statistical Manual of Mental Disorders.3rd ed, rev. American Psychiatric Press, New York1987
- Evidence for anticipation in schizophrenia.Am J Hum Genet. 1994; 54: 864-870
- Statistical Power Analysis for the Behavioral Sciences.2nd ed. Lawrence Erlbaum Associates, Washington, DC1988
- Mathematical limits of multilocus models: The genetic transmission of bipolar disorder.Am J Hum Genet. 1995; 57: 690-702
- Concurrent validity of the OPCRIT diagnostic system: Comparison of OPCRIT diagnoses with consensus best-estimate lifetime diagnoses.Br J Psychiatry. 1996; 169: 58-63
- A diagnostic interview.Arch Gen Psychiatry. 1978; 35: 837-844
- Detection of expanded CAG repeats in bipolar affective disorder using the repeat expansion detection (RED) method.Neurobiol Dis. 1995; 2: 55-62
- A polydiagnostic application of operational criteria in studies of psychotic illness.Arch Gen Psychiatry. 1991; 48: 764-770
- Anticipation in bipolar affective disorder.Am J Hum Genet. 1993; 53: 385-390
- CAG repeat expansions and schizophrenia: Association with disease in females and with early age-at-onset.Hum Mol Genet. 1995; 4: 1957-1961
- Hereditary aspects of nervous and mental diseases.Br Med J. 1910; ii: 1013-1020
- Anticipation in Swedish families with bipolar affective disorder.J Med Genet. 1994; 31: 686-689
- Dynamic mutations and psychiatric genetics.Psychol Med. 1996; 26: 1-6
- Expanded CAG repeats in schizophrenia and bipolar disorder.Nat Genet. 1995; 10: 380-381
- Confirmation of association between expanded CAG/CTG repeats and both schizophrenia and bipolar disorder.Psychol Med. 1996; 26: 1145-1153
- Direct detection of novel expanded trinucleotide repeats in human genome.Nat Genet. 1993; 4: 135-139
- Repeat expansion detection using Ampligase thermostable DNA ligase.Epicenter Forum. 1995; 2: 1-3
- Further evidence for anticipation in schizophrenia.Psychiatry Res. 1995; 59: 25-33
- Schedules for Clinical Assessment in Neuropsychiatry.Arch Gen Psychiatry. 1990; 47: 589-593
Article Info
Publication History
Received in revised form:
November 13,
1996
Received:
April 15,
1996
Identification
Copyright
© 1997 Society of Biological Psychiatry. Published by Elsevier Inc.
