Am J Psychiatry 1996; 153:1173-1177
Copyright © 1996 by American Psychiatric Association
Anticipation in schizophrenia: new light on a controversial problem [published erratum appears in Am J Psychiatry 1997 Apr;154(4):590]
P Gorwood, M Leboyer, B Falissard, M Jay, F Rouillon and J Feingold
Laboratoire d'Epidemiologie Genetique, Institut National de la Sante et de la Recherche Medicale, Paris, France.
OBJECTIVE: Anticipation, recently found in several neuropsychiatric
disorders, is an inheritance pattern within a pedigree in which disease
severity increases or age at onset decreases in successive generations.
Demonstration of genetic anticipation in schizophrenia could be of
heuristic value, since unstable trinucleotide repeat DNA is known to be the
biological basis of anticipation. However, to overcome one of the major
ascertainment biases that might mimic anticipation--namely, the fact that
patients in different generations are not interviewed at the same age,
resulting in a greater chance of finding a later age at onset in the older
generation--a new method of investigating anticipation was used. METHOD:
The study subjects were 97 systematically ascertained schizophrenic
patients belonging to 24 families with at least two generations affected
who were identified during a 1-year prevalence study in a limited
geographical area of Reunion Island (Indian Ocean). A method of calculating
expected age at onset according to age at interview was used in the
analyses. RESULTS: In the younger generation of patients, the observed age
at onset (21.80 years) was earlier than the expected age at onset (24.95
years), demonstrating anticipation, even when five additional biases that
can mimic this genetic effect-- the proband effect, the presence of an
affected father or mother, the bilineality of the illness, the fertility
effect, and the cohort effect- -were taken into account. CONCLUSIONS:
Evidence for anticipation was demonstrated in this group of schizophrenic
patients. This may help the search for pathological genes implicated in the
genesis of schizophrenia.
