Advertisement

Expanded CAG/CTG repeats in bipolar disorder: No correlation with phenotypic measures of illness severity

      This paper is only available as a PDF. To read, Please Download here.
      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.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • American Psychiatric Association
        Diagnostic and Statistical Manual of Mental Disorders.
        3rd ed, rev. American Psychiatric Press, New York1987
        • Bassett AS
        • Honer WG
        Evidence for anticipation in schizophrenia.
        Am J Hum Genet. 1994; 54: 864-870
        • Cohen J
        Statistical Power Analysis for the Behavioral Sciences.
        2nd ed. Lawrence Erlbaum Associates, Washington, DC1988
        • Craddock N
        • Khodel V
        • Van Eerdewegh P
        • Reich T
        Mathematical limits of multilocus models: The genetic transmission of bipolar disorder.
        Am J Hum Genet. 1995; 57: 690-702
        • Craddock N
        • Asherson P
        • Owen MJ
        • Williams J
        • McGuffin P
        • Farmer AE
        Concurrent validity of the OPCRIT diagnostic system: Comparison of OPCRIT diagnoses with consensus best-estimate lifetime diagnoses.
        Br J Psychiatry. 1996; 169: 58-63
        • Endicott J
        • Spitzer RL
        A diagnostic interview.
        Arch Gen Psychiatry. 1978; 35: 837-844
        • Lindblad K
        • Nylander P-O
        • De bruyn A
        • et al.
        Detection of expanded CAG repeats in bipolar affective disorder using the repeat expansion detection (RED) method.
        Neurobiol Dis. 1995; 2: 55-62
        • McGuffin P
        • Farmer A
        • Harvey I
        A polydiagnostic application of operational criteria in studies of psychotic illness.
        Arch Gen Psychiatry. 1991; 48: 764-770
        • McInnis MG
        • McMahon FJ
        • Chase GA
        • Simpson SG
        • Ross CA
        • Depaulo JR
        Anticipation in bipolar affective disorder.
        Am J Hum Genet. 1993; 53: 385-390
        • Morris AG
        • Gaitonde E
        • McKenna PJ
        • Mollon JD
        • Hunt DM
        CAG repeat expansions and schizophrenia: Association with disease in females and with early age-at-onset.
        Hum Mol Genet. 1995; 4: 1957-1961
        • Mott FW
        Hereditary aspects of nervous and mental diseases.
        Br Med J. 1910; ii: 1013-1020
        • Nylander PO
        • Engstrom C
        • Chotai J
        • Wahlstrom J
        • Adolfsson R
        Anticipation in Swedish families with bipolar affective disorder.
        J Med Genet. 1994; 31: 686-689
        • O'Donovan MC
        • Owen MJ
        Dynamic mutations and psychiatric genetics.
        Psychol Med. 1996; 26: 1-6
        • O'Donovan MC
        • Guy C
        • Craddock N
        • et al.
        Expanded CAG repeats in schizophrenia and bipolar disorder.
        Nat Genet. 1995; 10: 380-381
        • O'Donovan MC
        • Guy C
        • Craddock N
        • et al.
        Confirmation of association between expanded CAG/CTG repeats and both schizophrenia and bipolar disorder.
        Psychol Med. 1996; 26: 1145-1153
        • Schalling M
        • Hudson TJ
        • Buetow KH
        • Housman DE
        Direct detection of novel expanded trinucleotide repeats in human genome.
        Nat Genet. 1993; 4: 135-139
        • Sirugo G
        • Kidd KK
        Repeat expansion detection using Ampligase thermostable DNA ligase.
        Epicenter Forum. 1995; 2: 1-3
        • Thibaut F
        • Martinez M
        • Petit M
        • Jay M
        • Campion D
        Further evidence for anticipation in schizophrenia.
        Psychiatry Res. 1995; 59: 25-33
        • Wing JK
        • Babor T
        • Brugha T
        • et al.
        Schedules for Clinical Assessment in Neuropsychiatry.
        Arch Gen Psychiatry. 1990; 47: 589-593