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Parental age and risk of schizophrenia: a case-control study.
Arch Gen Psychiatry 2003; 60(7):673-8AG

Abstract

BACKGROUND

Advanced paternal age has been suggested as a possible risk factor for schizophrenia. It is not known whether this is explained by known risk factors for schizophrenia, including sibship characteristics, death of a parent before first hospital admission, season and place of birth, and family history of psychiatric illness, or by socioeconomic factors. We investigated the risk of schizophrenia associated with parental age, adjusting for known risk factors for schizophrenia, including family psychiatric history, and controlling for socioeconomic and demographic factors.

METHODS

We performed a national population, nested, case-control study based on Danish longitudinal register data. The sample included 7704 patients with an ICD-8 or ICD-10 diagnosis of schizophrenia admitted to a psychiatric facility between 1981 and 1998 in Denmark, and 192 590 individually time-, age-, and sex-matched population controls, their parents, and siblings. The risk of schizophrenia associated with increasing parental age was investigated using conditional logistic regression and controlling for family socioeconomic and demographic factors and family psychiatric history.

RESULTS

Advanced paternal and maternal age was associated with increased risk of schizophrenia in univariate analyses. Controlling for socioeconomic factors and family psychiatric history, increased risk of schizophrenia was identified in those with a paternal age of 50 years or older. Sex-specific analyses revealed that the risk of schizophrenia was increased for males with fathers 55 years or older (incidence rate ratio [IRR], 2.10; 95% confidence interval [CI], 1.35-3.28); for females, the risk associated with paternal age was substantial for fathers aged 50 to 54 years (IRR, 2.22; 95% CI, 1.44-3.44) and 55 years or older (IRR, 3.53; 95% CI, 1.82-6.83).

CONCLUSION

Increased risk of schizophrenia was associated with advanced paternal age, particularly in females, lending support to the theory that de novo mutations, possibly X-linked, associated with increased parental age might be responsible for some cases of schizophrenia.

Authors+Show Affiliations

National Centre for Register-based Research, Aarhus University, Aarhus, Denmark. mb@ncrr.dkNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12860771

Citation

Byrne, Majella, et al. "Parental Age and Risk of Schizophrenia: a Case-control Study." Archives of General Psychiatry, vol. 60, no. 7, 2003, pp. 673-8.
Byrne M, Agerbo E, Ewald H, et al. Parental age and risk of schizophrenia: a case-control study. Arch Gen Psychiatry. 2003;60(7):673-8.
Byrne, M., Agerbo, E., Ewald, H., Eaton, W. W., & Mortensen, P. B. (2003). Parental age and risk of schizophrenia: a case-control study. Archives of General Psychiatry, 60(7), pp. 673-8.
Byrne M, et al. Parental Age and Risk of Schizophrenia: a Case-control Study. Arch Gen Psychiatry. 2003;60(7):673-8. PubMed PMID: 12860771.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Parental age and risk of schizophrenia: a case-control study. AU - Byrne,Majella, AU - Agerbo,Esben, AU - Ewald,Henrik, AU - Eaton,William W, AU - Mortensen,Preben Bo, PY - 2003/7/16/pubmed PY - 2003/9/17/medline PY - 2003/7/16/entrez SP - 673 EP - 8 JF - Archives of general psychiatry JO - Arch. Gen. Psychiatry VL - 60 IS - 7 N2 - BACKGROUND: Advanced paternal age has been suggested as a possible risk factor for schizophrenia. It is not known whether this is explained by known risk factors for schizophrenia, including sibship characteristics, death of a parent before first hospital admission, season and place of birth, and family history of psychiatric illness, or by socioeconomic factors. We investigated the risk of schizophrenia associated with parental age, adjusting for known risk factors for schizophrenia, including family psychiatric history, and controlling for socioeconomic and demographic factors. METHODS: We performed a national population, nested, case-control study based on Danish longitudinal register data. The sample included 7704 patients with an ICD-8 or ICD-10 diagnosis of schizophrenia admitted to a psychiatric facility between 1981 and 1998 in Denmark, and 192 590 individually time-, age-, and sex-matched population controls, their parents, and siblings. The risk of schizophrenia associated with increasing parental age was investigated using conditional logistic regression and controlling for family socioeconomic and demographic factors and family psychiatric history. RESULTS: Advanced paternal and maternal age was associated with increased risk of schizophrenia in univariate analyses. Controlling for socioeconomic factors and family psychiatric history, increased risk of schizophrenia was identified in those with a paternal age of 50 years or older. Sex-specific analyses revealed that the risk of schizophrenia was increased for males with fathers 55 years or older (incidence rate ratio [IRR], 2.10; 95% confidence interval [CI], 1.35-3.28); for females, the risk associated with paternal age was substantial for fathers aged 50 to 54 years (IRR, 2.22; 95% CI, 1.44-3.44) and 55 years or older (IRR, 3.53; 95% CI, 1.82-6.83). CONCLUSION: Increased risk of schizophrenia was associated with advanced paternal age, particularly in females, lending support to the theory that de novo mutations, possibly X-linked, associated with increased parental age might be responsible for some cases of schizophrenia. SN - 0003-990X UR - http://www.unboundmedicine.com/medline/citation/12860771/full_citation L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=12860771.ui DB - PRIME DP - Unbound Medicine ER -