Dolores Malaspina "It is well established that paternal age is the major source of de novo mutations in the human population"

Seminal findings
We initially examined the relationship between paternal age and the risk for schizophrenia because it is well established that paternal age is the major source of de novo mutations in the human population, and most schizophrenia cases have no family history of psychosis. In 2001, we demonstrated a monotonic increase in the risk of schizophrenia as paternal age advanced in the rich database of the Jerusalem Perinatal Cohort. Compared with the offspring of fathers aged 20-24 years, in well-controlled analyses, each decade of paternal age multiplied the risk for schizophrenia by 1.4 (95 percent confidence interval: 1.2-1.7), so that the relative risk (RR) for offspring of fathers aged 45+ was 3.0 (1.6-5.5), with 1/46 of these offspring developing schizophrenia. There were no comparable maternal age effects (Malaspina et al., 2001).

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Paternal age, size at birth, and size in young adulthood - risk factors for schizophrenia.Rasmussen F.
Child and Adolescent Public Health Epidemiology Group, Department of Public Health Sciences, Karolinska Institute, Norrbacka, SE-17176 Stockholm, Sweden.

It is appropriate to consider schizophrenia a neurodevelopmental disorder
In fully adjusted analyses, the risk of schizophrenia was 4.62 (95% confidence interval : 2.28; 9.36) times higher in subjects whose fathers were >/=50 years old and at time of conception than in subjects whose fathers were 21-24 years old. Growth and development in fetal life and childhood are influencing the risk of schizophrenia in adulthood, but the underlying causal pathways are still unknown. De novo mutations in the germ cells of older fathers may play a causal role in the etiology of some cases of schizophrenia.