ANTICIPATION IN SCHIZOPHRENIA - BIOLOGY OR BIAS

Anticipation is a genetic phenomenon wherein age of disease onset decr eases and/ or severity increases in successive generations, Anticipati on has been demonstrated for several neuropsychiatric disorders with e xpanding trinucleotide repeats recently identified as the underlying m olecular mechanism, We report here the results of an analysis of antic ipation performed with multiplex families segregating schizophrenia. T hirty-three families were identified through the NIMH Genetics Initiat ive that met the following criteria: had at least two affected members in successive generations and were not bilineal, Affectation diagnose s included schizophrenia, schizoaffective disorder-depressed, and psyc hosis NOS, Additional analyses included the Cluster A personality diso rders. Three indices of age of onset were used, Disease severity was m easured by several different indices. Four sampling schemes as suggest ed by McInnis et al, were tested, as well as additional analysis using pairs ascertained through the parental generation, Anticipation was d emonstrated for age of onset, regardless of the index or sampling sche me used (P < 0.05). Anticipation was not supported for disease severit y, Analyses that took into account drug use and diminished fecundity d id not affect the results, While the data strongly support intergenera tional differences in disease onset consistent with anticipation, they must be viewed cautiously given unavoidable biases attending these an alyses, Am, J. Med, Genet. 74:275-280, 1997. (C) 1997 Wiley-Liss, Inc.