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Anticipation in multiplex schizophrenia pedigrees

J Yaw1, M Myles-Worsley, M Hoff

  • 1Department of Psychiatry, University of Utah School of Medicine, Salt Lake City 84132, USA.

Psychiatric Genetics
|January 1, 1996
PubMed
Summary

Anticipation, characterized by earlier onset and increased severity of inherited diseases across generations, was investigated in schizophrenia. While some evidence suggests anticipation in schizophrenia families, ascertainment bias remains a likely explanation for observed generational changes.

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Area of Science:

  • Genetics
  • Psychiatry
  • Neuroscience

Background:

  • Anticipation, the worsening of inherited disease symptoms and earlier age of onset across generations, is a significant concern in schizophrenia.
  • This phenomenon is linked to the expansion of unstable trinucleotide repeat sequences, suggesting a genetic mutation's role in schizophrenia predisposition.
  • Previous studies on anticipation in schizophrenia families have yielded conflicting results, indicating potential occurrence in specific subsets.

Purpose of the Study:

  • To investigate the phenomenon of anticipation in families with schizophrenia.
  • To explore potential genetic mechanisms, such as trinucleotide repeat expansions, underlying anticipation in schizophrenia.
  • To differentiate between true anticipation and ascertainment bias in schizophrenia inheritance patterns.

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Main Methods:

  • Analysis of age of onset and symptom severity across generations in schizophrenia families.
  • Examination of early-onset parents to assess for ascertainment bias.
  • Comparison of anticipation effects in mother-child versus father-child pairs to explore potential imprinting effects.

Main Results:

  • The study sample demonstrated a significant decrease in age of onset and an increase in symptom severity across generations.
  • No consistent anticipation effects were observed in the subgroup of early-onset parents, suggesting potential ascertainment bias.
  • A slight increase in anticipation was noted for mother-child pairs compared to father-child pairs, hinting at a possible imprinting effect, though not statistically robust in this small sample.

Conclusions:

  • The observed generational changes in schizophrenia, including decreased age of onset and increased severity, are likely attributable to ascertainment bias.
  • While a potential imprinting effect was suggested by mother-child pair data, the evidence for true anticipation in schizophrenia remains inconclusive.
  • Further research with larger sample sizes is warranted to definitively determine the role of anticipation and imprinting in the genetic transmission of schizophrenia.