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Paternal age and psychiatric disorders: findings from a Dutch population registry.

ABSTRACT: We measured the association between paternal age and schizophrenia (SCZ), autism spectrum disorders (ASD), major depressive disorder (MDD), and bipolar disorder (BPD) in the Dutch population.In total, 14231 patients and 56924 matched controls were collected and analyzed for an association with paternal age by logistic regression.ASD is significantly associated with increased paternal age: Older fathers >40 years of age have a 3.3 times increased odds of having a child with ASD compared to young fathers <20 years of age. SCZ has significant associations for fathers aged >35 years (OR=1.27, 95% Confidence Interval: 1.05 and 1.53). For MDD, both younger and older fathers have increased odds. No association was found for BPD.The effects of paternal age as a risk factor are different for ASD and SCZ on one hand, and the affective disorders on the other hand. Different types of association might indicate different biological or psychosocial mechanisms. Late paternity (associated with predispositions to psychiatric disorders) seems the most probable explanation for the association with paternal age.

SUBMITTER: Buizer-Voskamp JE

PROVIDER: S-EPMC3110532 | biostudies-other | 2011 Jul

REPOSITORIES: biostudies-other

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Paternal age and psychiatric disorders: findings from a Dutch population registry.

Buizer-Voskamp Jacobine E JE Laan Wijnand W Staal Wouter G WG Hennekam Eric A M EA Aukes Maartje F MF Termorshuizen Fabian F Kahn René S RS Boks Marco P M MP Ophoff Roel A RA

Schizophrenia research 20110412 2-3

<h4>Background</h4>We measured the association between paternal age and schizophrenia (SCZ), autism spectrum disorders (ASD), major depressive disorder (MDD), and bipolar disorder (BPD) in the Dutch population.<h4>Methods</h4>In total, 14231 patients and 56924 matched controls were collected and analyzed for an association with paternal age by logistic regression.<h4>Results</h4>ASD is significantly associated with increased paternal age: Older fathers >40 years of age have a 3.3 times increased ...[more]

PMID: 21489755

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Project description:ImportanceAdvancing paternal age is associated with increased genetic mutations during spermatogenesis, which research suggests may cause psychiatric morbidity in the offspring. The effects of advancing paternal age at childbearing on offspring morbidity remain unclear, however, because of inconsistent epidemiologic findings and the inability of previous studies to rigorously rule out confounding factors.ObjectiveTo examine the associations between advancing paternal age at childbearing and numerous indexes of offspring morbidity.Design, setting, and participantsWe performed a population-based cohort study of all individuals born in Sweden in 1973-2001 (N = 2,615,081), with subsets of the data used to predict childhood or adolescent morbidity. We estimated the risk of psychiatric and academic morbidity associated with advancing paternal age using several quasi-experimental designs, including the comparison of differentially exposed siblings, cousins, and first-born cousins.ExposurePaternal age at childbearing.Main outcomes and measuresPsychiatric (autism, attention-deficit/hyperactivity disorder, psychosis, bipolar disorder, suicide attempt, and substance use problem) and academic (failing grades and low educational attainment) morbidity.ResultsIn the study population, advancing paternal age was associated with increased risk of some psychiatric disorders (eg, autism, psychosis, and bipolar disorders) but decreased risk of the other indexes of morbidity. In contrast, the sibling-comparison analyses indicated that advancing paternal age had a dose-response relationship with every index of morbidity, with the magnitude of the associations being as large or larger than the estimates in the entire population. Compared with offspring born to fathers 20 to 24 years old, offspring of fathers 45 years and older were at heightened risk of autism (hazard ratio [HR] = 3.45; 95% CI, 1.62-7.33), attention-deficit/hyperactivity disorder (HR = 13.13; 95% CI, 6.85-25.16), psychosis (HR = 2.07; 95% CI, 1.35-3.20), bipolar disorder (HR = 24.70; 95% CI, 12.12-50.31), suicide attempts (HR = 2.72; 95% CI, 2.08-3.56), substance use problems (HR = 2.44; 95% CI, 1.98-2.99), failing a grade (odds ratio [OR] = 1.59; 95% CI, 1.37-1.85), and low educational attainment (OR = 1.70; 95% CI, 1.50-1.93) in within-sibling comparisons. Additional analyses using several quasi-experimental designs obtained commensurate results, further strengthening the internal and external validity of the findings.Conclusions and relevanceAdvancing paternal age is associated with increased risk of psychiatric and academic morbidity, with the magnitude of the risks being as large or larger than previous estimates. These findings are consistent with the hypothesis that new genetic mutations that occur during spermatogenesis are causally related to offspring morbidity.

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Paternal age and psychiatric disorders: findings from a Dutch population registry.

Publications

Paternal age and psychiatric disorders: findings from a Dutch population registry.

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