Paternal ages below or above 35 years old are associated with a different risk of schizophrenia in the offspring

Abstract 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.