title: Anticipation in schizophrenia: biology or bias?
abstract: Anticipation is a genetic phenomenon wherein age of disease onset decreases and/ or severity increases in successive generations. Anticipation has been demonstrated for several neuropsychiatric disorders with expanding trinucleotide repeats recently identified as the underlying molecular mechanism. We report here the results of an analysis of anticipation performed with multiplex families segregating schizophrenia. Thirty-three families were identified through the NIMH Genetics Initiative that met the following criteria: had at least two affected members in successive generations and were not bilineal. Affectation diagnoses included schizophrenia, schizoaffective disorder-depressed, and psychosis NOS. Additional analyses included the Cluster A personality disorders. Three indices of age of onset were used. Disease severity was measured by several different indices. Four sampling schemes as suggested by McInnis et al. were tested, as well as additional analysis using pairs ascertained through the parental generation. Anticipation was demonstrated for age of onset, regardless of the index or sampling scheme used (P<0.05). Anticipation was not supported for disease severity. Analyses that took into account drug use and diminished fecundity did not affect the results. While the data strongly support intergenerational differences in disease onset consistent with anticipation, they must be viewed cautiously given unavoidable biases attending these analyses.
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Johnson
authors.forename: J
authors.initials: J
authors.lastname: Cleary
authors.forename: H
authors.initials: H
authors.lastname: Ahsan
authors.forename: J
authors.initials: J
authors.lastname: Harkavy Friedman
authors.forename: D
authors.initials: D
authors.lastname: Malaspina
authors.forename: C R
authors.initials: CR
authors.lastname: Cloninger
authors.forename: S V
authors.initials: SV
authors.lastname: Faraone
authors.forename: M T
authors.initials: MT
authors.lastname: Tsuang
authors.forename: C A
authors.initials: CA
authors.lastname: Kaufmann
mesh_terms: D017668:Age of Onset; D015982:Bias; D005190:Family / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D009315:National Institute of Mental Health (U.S.); D012559:Schizophrenia / Q000235:genetics*; D012720:Severity of Illness Index; D013223:Statistics as Topic; D014481:United States