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Understanding the association between advanced paternal age and schizophrenia and bipolar disorder

Published online by Cambridge University Press:  04 March 2019

Mark Weiser ,
Daphna Fenchel ,
Or Frenkel Open the ORCID record for Or Frenkel [Opens in a new window] ,
Eyal Fruchter ,
Shimon Burshtein ,
Ariel Ben Yehuda ,
Rinat Yoffe ,
Tal Bergman-Levi ,
Abraham Reichenberg  and
Michael Davidson
...Show all authors
Mark Weiser*
Affiliation:
Department of Psychiatry, Chaim Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Daphna Fenchel
Affiliation:
Department of Psychiatry, Chaim Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel
Or Frenkel
Affiliation:
Department of Psychiatry, Chaim Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel
Eyal Fruchter
Affiliation:
IDF Medical Corps, Israel Department of Psychiatry, Rambam Medical Center, Haifa, Israel Rappaport School of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
Shimon Burshtein
Affiliation:
Department of Psychiatry, Chaim Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel
Ariel Ben Yehuda
Affiliation:
IDF Medical Corps, Israel
Rinat Yoffe
Affiliation:
Department of Mental Health, Ministry of Health, Israel
Tal Bergman-Levi
Affiliation:
Department of Mental Health, Ministry of Health, Israel
Abraham Reichenberg
Affiliation:
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA Seaver Autism Center for Research and Treatment at Mount Sinai, New York, NY, USA
Michael Davidson
Affiliation:
Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Sven Sandin
Affiliation:
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA Seaver Autism Center for Research and Treatment at Mount Sinai, New York, NY, USA Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
*
Author for correspondence: Mark Weiser, E-mail: [email protected]
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Abstract

Background

Previous studies reported an association between advanced paternal age at birth and increased risk for schizophrenia and bipolar disorder. While some hypothesize that this association is caused by de-novo mutations in paternal spermatozoa, others cite factors associated with psycho-social characteristics of fathers who have children at a late age. This study aims to test these hypotheses.

Methods

A historical-prospective, population-based cohort study, performed by linking the Israeli Draft Board Registry and the Israeli National Psychiatric Hospitalization Registry (N = 916 439; 4488 with schizophrenia, 883 with bipolar disorder). Odds ratios (OR) and two-sided 95% confidence intervals (CI) were calculated by logistic regression models, using paternal age as predictor and risk for later hospitalizations for schizophrenia or bipolar disorder as outcome measure. Models were first fitted unadjusted, then adjusted for paternal age at birth of the first child.

Results

In the unadjusted model, offspring of fathers aged 45 and above at birth had increased risk of schizophrenia (OR = 1.71, 95% CI 1.49–1.99) and bipolar disorder (OR = 1.63, 95% CI 1.16–2.24). However, taking into account paternal age at birth of first child, advanced paternal age was no longer associated with increased risk of schizophrenia (OR = 0.60, 95% CI 0.48–0.79) or bipolar disorder (OR = 1.03, 95% CI 0.56–1.90).

Conclusions

Controlling for paternal age at birth of the first offspring, advanced paternal age does not predict increased risk for schizophrenia or bipolar disorder. These data indicate that the association between advanced paternal age and having an offspring with schizophrenia and bipolar disorder is likely due to psychos-social factors, or common genetic variation associated with delayed initial fatherhood.

Keywords

Advanced paternal agebipolar disorderde-novo mutationspsychiatric epidemiologyschizophrenia
Type
Original Articles
Information
Psychological Medicine , Volume 50 , Issue 3 , February 2020 , pp. 431 - 437
Copyright
Copyright © Cambridge University Press 2019

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