Advanced paternal age increases risk of bipolar disorder in offspring.

ED FROM Frans EM, Sandin S, Reichenberg A, et al. Advancing paternal age and bipolar disorder. Arch Gen Psychiatry 2008;65:1034–40. Correspondence to: Emma M Frans, MMedSc, Department of Medical Epidemiology and Biostatistics, Karolinksa Institute, PO Box 281, SE-171 77 Stockholm, Sweden; [email protected] Source of funding: None reported. c A table is published online only at http://ebmh.bmj.com/content/vol12/issue2 C O M M EN TA R Y A dvanced paternal age has historically been examined in association with psychiatric disease in the offspring. However, most studies have suffered from methodological shortcomings and the ‘‘new wave’’ started in 2001 when Malaspina and colleagues, based on a large cohort, described an almost three times increased risk for the offspring to develop schizophrenia if the father was aged 50 years or older at the time of birth of the child. Since then at least six more studies have been published on the subject, all showing a dose– response relationship. Recently, an association with another neurodevelopmental disorder, autism spectrum disorder (ASD), was described. 3 Now Frans and colleagues present evidence of an association between paternal age and risk of bipolar disorder (BPD). There was a stepwise increased risk and offspring of fathers aged 55 years and older had an increased risk of 1.38. This is a somewhat lower risk estimate than those described in previous studies of schizophrenia. However, in subanalysis of BPD cases with ‘‘early onset’’, defined as hospitalised at an early age (,20 years), the effect was stronger (OR 2.63). In summary, there is now evidence of an association between advancing paternal age and risk of BPD, ASD and schizophrenia. This is intriguing and the question is, what do these psychiatric disorders have in common? One thing is a substantial genetic component. Two hypotheses about the underlying mechanisms of the paternal age effect are currently discussed: de novo mutations is one such hypothesis. In the production of sperms, the germ cells replicate regularly resulting in an increasing number of divisions by advancing age and thus the risk for DNA copy errors increases. Another hypothesis is that aberrant epigenetic regulation explains the association. Both of these mechanisms may lead to heritable changes and can explain how the illnesses are maintained in the population given the reduced fertility of those with some of the disorders. Christina Dalman, MD, PhD Department of Public Health Sciences, Karolinska Institutet., Stockholm, Sweden Competing interests: None. 1. Malaspina D, Harlap S, Fennig S, et al. Advancing paternal age and the risk of schizophrenia. Arch Gen Psychiatry 2001;58:361–7. 2. Reichenberg A, Gross R, Weiser M, et al. Advancing paternal age and autism. Arch Gen Psychiatry 2006;63: 1026–32. 3. Croen LA, Najjar DV, Fireman B, et al. Maternal and paternal age and risk of autism spectrum disorders. Arch Pediatr Adolesc Med 2007;161:334–40. Aetiology EBMH May 2009 Vol 12 No 2 59 group.bmj.com on June 20, 2017 Published by http://ebmh.bmj.com/ Downloaded from