BACKGROUND: A link between older age of fatherhood and an increased risk of schizophrenia was detected in 1958

If you want to avoid having non-familial autistic or schizophrenic or other types of damaged children be sure to father them in your 20s to very early 30s. By the age of 34 the risks are much higher than if you were 24. Aberrant Epigenetic Regulation Could Explain the Relationship of Paternal Age to Schizophrenia
Mary C. Perrin2, Alan S. Brown3,4 and Dolores Malaspina1,2
2 Department of Psychiatry, School of Medicine, New York University, New York, NY
3 New York State Psychiatric Institute, New York, NY
4 Department of Psychiatry, Columbia University, New York, NY

1 To whom correspondence should be addressed; tel: 212-263-6214, fax: 212-263-5717, e-mail: Dolores.Malaspina@NYUMC.ORG.

The causal mechanism underlying the well-established relation between advancing paternal age and schizophrenia is hypothesized to involve mutational errors during spermatogenesis that occur with increasing frequency as males age. Point mutations are well known to increase with advancing paternal age while other errors such as altered copy number in repeat DNA and chromosome breakage have in some cases also been associated with advancing paternal age. Dysregulation of epigenetic processes may also be an important mechanism underlying the association between paternal age and schizophrenia. Evidence suggests that advancing age as well as environmental exposures alter epigenetic regulation. Errors in epigenetic processes, such as parental imprinting can have serious effects on the offspring both pre- and postnatally and into adulthood. This article will discuss parental imprinting on the autosomal and X chromosomes and the alterations in epigenetic regulation that may lead to such errors.


Keywords: methylation / imprinting / X-chromosome inactivation / schizophrenia



Eur Psychiatry. 2007 Jan;22(1):22-6. Epub 2006 Dec 4. Links
Paternal ages below or above 35 years old are associated with a different risk of schizophrenia in the offspring.Wohl M, Gorwood P.
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BACKGROUND: A link between older age of fatherhood and an increased risk of schizophrenia was detected in 1958. Since then, 10 studies attempted to replicate this result with different methods, on samples with different origins, using different age classes. Defining a cut-off at which the risk is significantly increased in the offspring could have an important impact on public health. METHODS: A meta-analysis (Meta Win) was performed, assessing the mean effect size for each age class, taking into account the difference in age class references, and the study design. RESULTS: An increased risk is detected when paternal age is below 20 (compared to 20-24), over 35 (compared to below 35), 39 (compared to less than 30), and 54 years old (compared to less than 25). Interestingly, 35 years appears nevertheless to be the lowest cut-off where the OR is always above 1, whatever the age class reference, and the smallest value where offspring of fathers below or above this age have a significantly different risk of schizophrenia. CONCLUSION: No threshold can be precisely defined, but convergent elements indicate ages below or above 35 years. Using homogeneous age ranges in future studies could help to clarify a precise threshold.

PMID: 17142012 [PubMed - indexed for MEDLINE]