title: Sex-specific rates of transmission of psychosis in the New England high-risk family study.
abstract: Recent molecular genetic studies have demonstrated X-chromosome abnormalities in the transmission of psychosis, a finding that may contribute to understanding sex differences in the disorder. Using our family high risk paradigm, we tested the hypothesis that there are sex-specific patterns of transmission of psychosis and whether there is specificity comparing nonaffective- with affective-type psychoses. We identified 159 parents with psychoses (schizophrenia psychosis spectrum disorders (SPS, n=59) and affective (AP, n=100)) and 114 comparable, healthy control parents. 203 high risk (HR) and 147 control offspring were diagnostically assessed (185 females; 165 males). We compared the proportion of male:female offspring with psychoses by affected parent sex and the consistency for SPS compared to AP parents, and tested (using exact logistic regression) whether the male:female ratio for affected offspring differed significantly between affected mothers and affected fathers. Risk of psychosis in offspring was a function of the sex of the parent and offspring. Among ill mothers, 18.8% of their male offspring developed psychosis compared with 9.5% of their daughters. In contrast, among ill fathers, 3.1% of their male offspring developed psychosis compared with 15.2% of their daughters. The male:female ratio for affected offspring differed significantly (p < 0.05) between affected mothers and fathers. Similar patterns held for SPS and AP. Results demonstrated sex-specific transmission of psychosis regardless of psychosis-type and suggest X-linked inheritance. This has important implications for molecular genetic studies of psychoses underscoring the impact of one's gender on gene-brain-behavior phenotypes of SCZ.
authors.affiliation: Brigham and Women's Hospital Departments of Psychiatry and Medicine, Division of Women's Health, Connors Center for Women's Health and Gender Biology, Boston, MA 02120, USA. jill_goldstein@hms.harvard.edu
authors.forename: Jill M
authors.initials: JM
authors.lastname: Goldstein
authors.forename: Sara
authors.initials: S
authors.lastname: Cherkerzian
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Seidman
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Petryshen
authors.forename: Garrett
authors.initials: G
authors.lastname: Fitzmaurice
authors.forename: Ming T
authors.initials: MT
authors.lastname: Tsuang
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Buka
mesh_terms: D000328:Adult; D005192:Family Health; D005220:Fathers / Q000523:psychology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008297:Male; D009035:Mothers / Q000523:psychology; D009511:New England / Q000453:epidemiology; D011618:Psychotic Disorders / Q000453:epidemiology* / Q000235:genetics*; D012307:Risk Factors; D012727:Sex Characteristics; D055815:Young Adult