Thursday, April 03, 2008

Older Age of Father increases risk of Schizophrenia

Older Age of Father increases risk of Schizophrenia

Recent studies have indicated that children who are born to older fathers have a higher risk of schizophrenia. Researchers have suggested that the problem of damaged sperm could be the cause of approximately 15% to 25% of all cases of schizophrenia. This is believed to be due to the higher levels of DNA damage in the sperm of older men. Researchers estimate that compared to a male fathering a child in his early 20's - there is double the chance of the child getting schizophrenia when the father is age 40, and triple the risk of schizophrenia when the father is age 50. (though, for most people this means the risk goes from approximately 1 in 121 when a man is 29, to to 1 in 47 when a man is age 50 to 54).

Interestingly, Dr. Delores Malaspina noted in a recent Medscape interview that "The finding is that father's age is not connected to the risk of schizophrenia when it runs in families, but only for cases with no family history. That is called sporadic schizophrenia." She also noted "I would personally not discourage anyone from having a child at any age. People weigh their own risks. For the offspring of older fathers (over age 50), the risk of schizophrenia is about 3%. That means that 97% of the offspring do not have schizophrenia. Other cognitive diseases linked to paternal age include mental retardation of unknown etiology and Alzheimer's disease, and there is a strong relationship between paternal age and autism." Furthermore, stated Dr. Malaspina, "our hypothesis and model right now for how paternal age affects the risk for schizophrenia is that it has altered the expression of genes inherited from the father.

Even exposures that interact with genetic susceptibility may act by changing gene expression, such as traumatic brain injury, cannabis, and stress. Maybe we can integrate our understanding of the many exposures tied to schizophrenia and the many genes tied to schizophrenia with the understanding that certain exposures may act by changing gene expression."

Source: Paternal Age and Risk of Schizophrenia in Adult Offspring

Discover Magazine, in 2002 covered Columbia University researcher Dr. Delores Malaspina's work on this topic:

"Malaspina has found that about a quarter of all people that develop schizophrenia may owe their symptoms to spontaneous genetic mutations in paternal sperm. And the older the father, the more likely his sperm is to carry such mutations.

Malaspina consulted a national registry of mental illness maintained since 1950. At the time, isolated reports suggested that the youngest children in families have the highest risk of developing schizophrenia, but the reason for the trend was unclear. After poring over the medical records of more than 87,000 people born between 1964 and 1976 – 658 of whom had been diagnosed with schizophrenia or closely related psychoses – Malaspina reached a startling conclusion. Whereas one out of every 121 children born to men in their late twenties had developed schizophrenia by the age of 34, one of every 47 children born to men age 50 to 54 developed the disease. In other words, after age 50, a man’s risk of having schizophrenic offspring seems to be more than twice that of a man who reproduces in his late twenties.

Malaspina’s results were so surprising that some of her colleagues found them hard to digest. “Reproductive scientists in my department said ‘It can’t be,’” she recalls. Yet she had hit upon a phenomenon that geneticists had recognized for decades: Older fathers are far more likely than younger men to have children with genetic disorders. According to geneticist James Crow of the University of Wisconsin at Madison, paternal age is the source of genetic diseases caused by new dominant mutations. (Only one copy of a dominant mutant gene is necessary to induce disease.) Among the diseases more likely to occur in children with older fathers are achondroplasia (which causes dwarfism), progeria (premature aging), Marfan’s syndrome (a connective tissue disorder), a predisposition toward a certain type of skin cancer, and some congenital heart defects. All are triggered by simple deletions or substitutions of one DNA base – unlike Down’s syndrome, which is caused by the doubling of an entire chromosome and is usually inherited from the mother.

Why should mutations increase as fathers’ age? The answer lies in the life history of the sperm. By the time a man is 40, each of his sperm cell precursors, called spermatogonia, has divided approximately 660 times, or about 23 times a year after puberty, in order to give rise to sperm. By contrast, in a female, egg precursor cells divide only 24 times, all but one of these divisions occurring before she is born. The more replication, the greater the chance that a copying error – a mutation – will occur. To compound matters, DNA-repair enzymes become less efficient as a man ages and more frequently fail to fix a mutant sperm."



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