Older Age of Father increases risk of Schizophrenia

Overview of Research

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."

Helpful Actions: For reduced risk of children with schizophrenia, men should have children while they are younger, rather than older. If an older man is planning children he should (for several month prior to initiating the pregnancy) avoid hot saunas and whirlpools, bathtubs, etc. (because the heat can damage the sperm) and follow general male reproductive health recommendations. Related information and news follows:

Men wanting to become a father should avoid soaking in hot baths, according to a new study on male fertility. A three-year pilot project involving 11 men (age range: 31 to 44) found that there was some truth in the old wives' tale about hot baths being bad for a man's prospects of conceiving. The men were exposed to "wet heat" in the form of a hot tub, Jacuzzi or bath, at least once a week for 30 minutes or more for three months. Scientists studied sperm quantity and quality after the bathing stopped and found that five of the 11 men experienced a significant increase in fertility. After three to six months of staying out of the bath, the men's average active sperm count i"had a mean increase in total motile sperm counts of 491%." Of the 6 who didn't improve, 5 were chronic smokers. Conclusion: Take better care of your body.

Overweight couples are almost three times more likely to have trouble conceiving than couples of normal weight, according to new research. Being obese had more of an effect than being overweight but overweight couples struggled to get pregnant too, it found. It is the first study looking at the effects on fertility of fat couples, rather than just individuals. Researchers in Denmark studied 47,835 couples between 1996 and 2002 for the study, published online in the journal Human Reproduction. They found that if both partners were obese the likelihood of the couple having to wait more than a year before conceiving was almost three times higher than for a couple of normal weight. If both partners were overweight, the chance they would have to wait longer than a year was 1.4 times higher.

Taking anti-oxidant vitamins, eating healthy (low in saturated animal fat, low in simple carbohydrates) foods, and maintaining moderate weight (appropriate for height), and avoiding cigarette smoke and tobacco products, may help reduce DNA damage in sperm as a man grows older, but quantitative studies have not been done in this area. Well known antioxidants include Vitamin C, Vitamin E, Alpha Lipoic Acid. There have also been studies to suggest that 4 grams daily of Acetyl-L-Carnitine helps sperm motility (movement) - and may also be helpful. If Acetyl-L-Carnitine is taken, then the antioxidant Alpha Lipoic Acid should be taken with it (Dr. Bruce Ames of UC Berkeley suggests). Smoking and chewing tobacco can lower sperm count and increase the number of abnormal sperm a man produces, while heavy drinking can also damage sperm quality. Scientists at Buffalo University in the US found men who regularly smoke cannabis have a lower sperm count.

The average sperm count has dropped by half in the past 50 years, possibly because the nutritional value of the food we eat has declined," says Zita West, author of "Zita West's Guide To Getting Pregnant" . So try to get the nutrients you need. Zinc, which helps to form sperm, is particularly important for men and is found in meat, shellfish and dairy food.Men with a low sperm count often lack essential fatty acids in their diet, so eat more oily fish, seeds and nuts.

For men with low sperm counts, sexual abstinence -- but only for a day -- increases semen quality. More prolonged sexual abstinence may actually reduce sperm numbers, a new study indicates.

"After only two days of abstinence, sperm from patients with male factor infertility initiate a process of quality degradation," Dr. Eliahu Levitas of Soroka University Medical Center in Beer-Sheva, Israel, and colleagues report in the journal Fertility and Sterility. The findings are important for men trying to father children through in-vitro fertilization, or even through the natural method. The researchers conducted the current study to determine the effect of abstinence on sperm quality. Among the samples classified as being low sperm counts, peak sperm concentration and peak sperm motility occurred after one day of abstinence. The percentage of normal sperm also peaked at one to two days of abstinence for low-count men. Samples with normal sperm counts showed a slight decline in sperm concentration during two days of abstinence, followed by a gradual increase to a peak on days six and seven.

In June, 2005 an alert over foods containing soya was raised by scientists last night after it emerged they could affect fertility. A study found a chemical in soya can destroy the ability of human sperm to fertilise eggs. Experts believe couples trying for a baby should avoid eating soya products completely. Research from King's College, London, found women who ate the foods absorbed certain chemicals in their bloodstream. When they tried for a baby, these chemicals would attack their partner's sperm causing it to '"burn out" early. Soya is found in products for vegetarians and also in mainstream supermarket foods.

And - in a rather bizarre news item in 2005, it was reported that men may be capable of subconsciously increasing the quality of their semen when their sperm might have to compete.

Straight men produce better sperm when presented with pornography featuring men and women rather than pornography showing women alone. Although this is contrary to what most straight men would have believed, this is consistent with theories of sperm competition. Competition from other men stimulates production of higher quality semen, increasing the chances of procreation. Sarah Kilgallon and Leigh Simmons of the University of Western Australia, Perth, recruited 52 men. The men viewed explicit pictures that featured either two men and a woman or three women and collected a sperm sample. Although the number was the same, men who had viewed the images featuring both sexes had more motile sperm (Biology Letters , DOI: 10.1098/rsbl.2005.0324). Previous studies have shown that men tend to prefer the kind of "sperm competition" images used in the study. Men may have evolved to find them more erotic, Simmons speculates. The volunteers had previously abstained from sexual activity for two to six days. In samples from men who viewed the images containing the two men and a woman - the “sperm-competition” images - 52% of the sperm were motile. This compared with 49% sperm motility in the men who viewed the images of women only – a difference that was statistically significant after taking into account lifestyle factors such as cigarette smoking and alcohol consumption.

Supporting Research & News (a sample):





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