PARS PATERNAL AGE RELATED SCHIZOPHRENIA

In a cohort of 658 individuals in Israel diagnosed with schizophrenia,[15] paternal age was found to be a very strong predictor of the development of schizophrenia. Confounding factors, including maternal age, were controlled. Compared with fathers younger than 25 years old, the risk of schizophrenia increased with each 5-year age interval. The risk of a child developing schizophrenia was 2.02 times more likely if the father was aged 45-49 years and 2.96 times more likely in fathers older than 50 years. In a Swedish study,[16] similar increased rates were found. The likelihood that fathers older than 45 years had offspring with schizophrenia was 2.8-fold more than younger fathers. Zammit and colleagues[17] also found that there was a "dose-dependent" risk of increase in schizophrenia with increased paternal age. Each 10-year increase in paternal age resulted in a 1.3 odds ratio of increased risk. Other genetic disorders such as Down's syndrome are also associated with increased paternal age.[18]
A woman's egg cell undergoes very few divisions. In contrast, spermatogenesis is a lifelong process, with another replication every 16 days. A mutation that occurs in one of the spermatogonia will be passed along to subsequent generations of sperm. Therefore, as the male ages, there is more of a probability of a mutation occurring.

Animal models lend support to the differential effect of paternal age on central nervous system function. In inbred mice strains, paternal age was a strong predictor of central nervous system function. Negative effects were noted on factors such as learning tasks, exploratory behavior, and startle response latencies. This effect was not passed onto future generations of mice, however. The mice offspring of disturbed mice reverted to normal. Thus, there appear to be other factors other than a specific mutation occurring. Paternal age may have an effect on the expression of genes as well as the genetic transmission of traits.

Dr. Malaspina reported on ongoing work delineating characteristics that might distinguish individuals with paternal age-related schizophrenia (PARS) from individuals with schizophrenia with an affected first-degree relative.[15]