Paternal age and risk of schizophrenia in adult offspring.

OBJECTIVE The study examined the relation between paternal age at the time of birth and risk of schizophrenia in the adult offspring. METHOD Data from the birth cohort of the Prenatal Determinants of Schizophrenia study were used in this study. Virtually all members of this birth cohort had prospective information about paternal age at the time of the offspring's birth. Subjects with schizophrenia and other schizophrenia spectrum disorders (N=71) among members of this birth cohort were previously ascertained. In separate analyses, paternal age was modeled as a continuous variable and as a categorical variable, and its relation with the risk of adult schizophrenia and other schizophrenia spectrum disorders and with the risk of schizophrenia separately were examined. RESULTS There was a marginally significant, monotonic association between advancing paternal age and risk of adult schizophrenia and schizophrenia spectrum disorders. The association held after the analysis controlled for the effects of maternal age and other potential confounders. Similar results were observed when only subjects with schizophrenia were included in the analysis. CONCLUSIONS Advanced paternal age at the time of birth of the offspring may be a risk factor for adult schizophrenia.

[1]  D. Collet.  Modelling Survival Data in Medical Research , 2004 .

[2]  Laurence L. George,et al.  The Statistical Analysis of Failure Time Data , 2003, Technometrics.

[3]  E. Susser,et al.  Advancing paternal age and the risk of schizophrenia. , 2001, Archives of general psychiatry.

[4]  L. Cupples,et al.  Parental age at child's birth and son's risk of prostate cancer. The Framingham Study. , 1999, American journal of epidemiology.

[5]  K. Plant,et al.  The fertility and fecundity of patients with psychoses , 1999, Acta psychiatrica Scandinavica.

[6]  J. Goldblatt,et al.  Craniosynostosis in Western Australia, 1980-1994: a population-based study. , 1999, American journal of medical genetics.

[7]  A. Munnich,et al.  Mutations in fibroblast growth-factor receptor 3 in sporadic cases of achondroplasia occur exclusively on the paternally derived chromosome. , 1998, American journal of human genetics.

[8]  A. Kurz,et al.  Paternal age is a risk factor for Alzheimer disease in the absence of a major gene , 1998, Neurogenetics.

[9]  J. A. Harris,et al.  Birth prevalence, mutation rate, sex ratio, parents' age, and ethnicity in Apert syndrome. , 1997, American journal of medical genetics.

[10]  J. Crow.  The high spontaneous mutation rate: is it a health risk? , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Steven A. Wall,et al.  Exclusive paternal origin of new mutations in Apert syndrome , 1996, Nature Genetics.

[12]  K. Kendler,et al.  Evaluating the spectrum concept of schizophrenia in the Roscommon Family Study. , 1995, The American journal of psychiatry.

[13]  A. Olshan,et al.  PATERNAL AGE AND THE RISK OF BIRTH DEFECTS IN OFFSPRING , 1995, Epidemiology.

[14]  J. Brar,et al.  Reduced fertility in schizophrenia: Here to stay? , 1995, Schizophrenia Research.

[15]  L. Fañanás,et al.  Parental age in schizophrenia in a case-controlled study , 1993, British Journal of Psychiatry.

[16]  D. Savitz,et al.  Influence of paternal age, smoking, and alcohol consumption on congenital anomalies. , 1991, Teratology.

[17]  M. Zack,et al.  Paternal age and the occurrence of birth defects. , 1986, American journal of human genetics.

[18]  M. Baron,et al.  A family study of schizophrenic and normal control probands: implications for the spectrum concept of schizophrenia. , 1985, The American journal of psychiatry.

[19]  M. Tsuang,et al.  The association between early parental loss and diagnosis in the Iowa 500. , 1983, Archives of general psychiatry.

[20]  H. Vogel.  Fertility and sibship size in a psychiatric patient population| A COMPARISON WITH NATIONAL CENSUS DATA , 1979, Acta psychiatrica Scandinavica.

[21]  P. Moran,et al.  Raised Parental Age in Psychiatric Patients: Evidence for the Constitutional Hypothesis , 1979, British Journal of Psychiatry.

[22]  A. Polednak.  Paternal age in relation to selected birth defects. , 1976, Human biology.

[23]  P. Wender.  Genetics and schizophrenia. , 1973, JAMA.

[24]  F. Fraser,et al.  Paternal age and congenital cleft lip and cleft palate. , 1972, Teratology.

[25]  J. Price,et al.  Marriage and fertility of psychiatric patients compared with national data. , 1971, Social biology.

[26]  J. Price,et al.  Marital status of first admissions to psychiatric beds in England and Wales in 1965 and 1966. , 1971, Social Biology.

[27]  K. Granville-Grossman,et al.  Parental Age and Schizophrenia , 1966, British Journal of Psychiatry.

[28]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[29]  L. Penrose.  Parental age and mutation. , 1955, Lancet.

[30]  Ø. Ødegård.  New data on marriage and mental disease: the incidence of psychoses in the widowed and the divorces. , 1953, The Journal of mental science.

[31]  E. Susser,et al.  The design of the prenatal determinants of schizophrenia study. , 2000, Schizophrenia bulletin.

[32]  K. Kendler,et al.  Schizotypal personality disorder in parents and the risk for schizophrenia in siblings. , 1995, Schizophrenia bulletin.

[33]  J. Friedman.  Genetic disease in the offspring of older fathers. , 1981, Obstetrics and gynecology.

[34]  I. Gregory.  An analysis of family data on 1000 patients admitted to a Canadian mental hospital. , 1959, Acta genetica et statistica medica.

[35]  E. Johanson.  A study of schizophrenia in the male: a psychiatric and social study based on 138 cases with follow up. , 1958, Acta psychiatrica et neurologica Scandinavica. Supplementum.

[36]  J. A. Book.  Schizophrenia as a gene mutation. , 1953, Acta genetica et statistica medica.