Advanced paternal age

Advanced paternal age
In recent years, several high-quality studies have confirmed an association between advanced paternal age and increased risk of schizophrenia.22-24 The association between paternal age and schizophrenia has been repeatedly shown to be present in those with no family history of the disorder, but not in those with a positive family history. This finding raises the possibility that accumulation of de-novo mutations in paternal sperm with ageing contributes to the risk of schizophrenia. The strengthened evidence linking advanced paternal age and schizophrenia has influenced a range of aetiological theories of schizophrenia. For example, the persistence of schizophrenia in the population in spite of reduced fertility could be explained by the transgenerational accumulation of paternally-derived mutations. Paternal exposure to micronutritional deficiencies such as folate could further amplify copy-error mutations in the male germ cell lines. Finally, it is also feasible that epigenetic processes (eg, chromatin folding, methylation of CpG bases) could be compromised in the sperm of older fathers, and that these mechanisms may contribute to the increased risk of schizophrenia in the offspring of older
fathers.

Med J Aust. 2009 Feb 16;190(4):S7-S9.
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New directions in the epidemiology of schizophrenia.
McGrath JJ, Susser ES.
Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia. john_mcgrath@qcmhr.uq.edu.au.
New primary data and systematic reviews have prompted the review of some long-held views about the epidemiology of schizophrenia. The incidence and prevalence of schizophrenia show prominent variation between locations. Males are more likely to develop schizophrenia than females (1.4 : 1). Migrant status, urban birth or residence, and advanced paternal age are associated with an increased risk of developing schizophrenia. Prenatal infection and nutrition are associated with an increased risk of schizophrenia. Individuals with schizophrenia have a 2-3-fold increased mortality risk compared with the general population. This differential mortality gap may have worsened in recent decades. Epidemiology is good for generating candidate exposures but poor at proving them. Cross-disciplinary projects between epidemiology and neuroscience may help us understand the pathways leading to schizophrenia.
PMID: 19220176 [PubMed - as supplied by publisher]
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