What is the truth about autism and schizophrenia and other genetic disorders such as type 1 diabetes?

"Finally, we examined if paternal age was related to the risk for autism in our cohort. We found very strong effects of advancing paternal age on the risk for autism and related pervasive developmental disorders (Reichenberg et al., in press). Compared to the offspring of fathers aged 30 years or younger, the risk was tripled for offspring of fathers in their forties and was increased fivefold when paternal age was >50 years. Together, these studies provide strong and convergent support for the hypothesis that later paternal age can influence neural functioning. The translational animal model offers the opportunity to identify candidate genes and epigenetic mechanisms that may explain the association of cognitive functioning with advancing paternal age."




"Paternal age at conception is a robust risk factor for schizophrenia. Possible mechanisms include de novo point mutations or defective epigenetic regulation of paternal genes. The predisposing genetic events appear to occur probabilistically (stochastically) in proportion to advancing paternal age, but might also be induced by toxic exposures, nutritional deficiencies, suboptimal DNA repair enzymes, or other factors that influence the

fidelity of genetic information in the constantly replicating male germ line. We propose that de novo genetic alterations in the paternal germ line cause an independent and common variant of schizophrenia.

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.

The most irrefutable finding is our demonstration that a father’s age is a major risk factor for schizophrenia. We were the first group to show that schizophrenia is linearly related to paternal age and that the risk is tripled for the offspring of the oldest groups of fathers.7 This finding has been born out in every single cohort study that has looked at paternal age and the risk for schizophrenia. The only other finding that has been as consistently replicated in schizophrenia research is that there is an increased risk associated with a family history of schizophrenia. Since only 10% to 15% of schizophrenia cases have a family history, family history does not explain much of the population risk for schizophrenia. However, we think that approximately one third or one quarter of all schizophrenia cases may be attributable to paternal age. Paternal age is the major source of de novo genetic diseases in the human population, which was first described by Penrose8 in the 1950s. He hypothesized that this was due to copy errors that arose in the male germ line over the many cycles of sperm cell replications. These mutations accumulate as paternal age advances. After the Penrose report, medical researchers identified scores of sporadic diseases in the offspring of older fathers, suggesting that these could occur from gene mutations. Particular attention was paid to conditions in last-born children. In the 1960s, an excess of schizophrenia in last-born children was also reported."



Clinical Psychology and Psychiatry Blogspot

A good chunk of studies have accumulated over the past few years (e.g., 1, 2, 3, 4, 5) that show a strong link between increasing paternal (father’s) age and risk of schizophrenia in children.
One researcher has described the link as follows:



We found that paternal age explained over a quarter of the risk for schizophrenia in the population. At the time, people were skeptical. But the findings have been replicated many times now, and not a single study has failed to find this strong relationship between father's age and the risk for schizophrenia. And at this point, other explanations for the relationship have been ruled out, including social factors in the family, prenatal care, and parental psychiatric ailments. There simply seems to be a relationship between paternal age and schizophrenia risk.

Wow – one quarter of the risk for schizophrenia explained by paternal age? I’ll admit that these types of studies are not my area of expertise, but from my review of some of these studies, I’m willing to buy that paternal age is a significant risk. These findings have indeed been replicated on numerous occasions.


One of the main researchers in the area, Dolores Malaspina (quoted above), has said that findings such as this should not discourage parents from having children at whatever age they choose. I am not in agreement – older parents should be made aware of the risk and make an informed decision.


Why the effect? Here’s what seems to be a decent explanation…


"Every cell division makes a copy of DNA," [researcher] Gavrilova says. "And the same thing happens with the next division and this final copy is of less quality. This can introduce a slight risk of error in the genetic material of the new sperm. You can call it a kind of copy error.

The longer a man ages, the greater the chance of sperm mutations that could lead to schizophrenia or other problems in offspring.

There is also research linking autism to older fathers. It appears that such information is not widely known. I was certainly not familiar with it until recently. Consider the trends in Western societies – fathers having children at older ages is likely leading to a decent sized increase in rates of schizophrenia, autism, and perhaps other problems as well. While this is excellent news if one is in the antipsychotic business, is this really good news for everyone else?


Shouldn't this information be more widely discussed?........................