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Anticipation in bipolar affective disorder
M G McInnis1, F J McMahon, G A Chase
1Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287-7463.
American Journal of Human Genetics
|August 1, 1993
Summary
Genetic anticipation, a worsening of bipolar disorder (BPAD) across generations, was confirmed in families. The second generation experienced significantly earlier onset and increased severity, suggesting trinucleotide repeat expansions may play a role.
Area of Science:
- Genetics
- Psychiatry
- Medical Research
Background:
- Anticipation, characterized by earlier onset and increased severity in successive generations, has been observed in various genetic disorders.
- Trinucleotide repeat sequences (TNRs) expansion is a known mechanism underlying anticipation in some inherited conditions.
- The presence of anticipation in bipolar affective disorder (BPAD) could offer crucial insights into its complex genetic underpinnings.
Purpose of the Study:
- To investigate the phenomenon of genetic anticipation in bipolar affective disorder (BPAD).
- To compare the age at onset and disease severity between two generations within unilineal BPAD families.
- To explore potential genetic mechanisms, such as TNR expansions, contributing to BPAD etiology.
Main Methods:
- A comparative study of 34 unilineal families ascertained for a genetic linkage study of BPAD.
- Life-table analyses were employed to assess survival to first manic or depressive episode across generations.
- Intergenerational pairwise comparisons evaluated differences in age at onset and disease severity, with robust statistical sampling schemes.
Main Results:
- A statistically significant decrease in survival to first episode (mania or depression) was observed from the first to the second generation (P < .001).
- The second generation exhibited a significantly earlier age at onset (P < .001) and markedly increased disease severity (P < .001) compared to the first generation.
- Onset occurred 8.9-13.5 years earlier, and illness was 1.8-3.4 times more severe in the second generation, with findings unaffected by confounding factors.
Conclusions:
- The study provides strong evidence for genetic anticipation occurring in this sample of unilineal BPAD families.
- These findings suggest that genes involving expanding trinucleotide repeat sequences may be implicated in the genetic etiology of bipolar affective disorder.
- Further research into TNR dynamics in BPAD is warranted to elucidate the precise genetic mechanisms.