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Harvard Commentaries
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Harvard Commentaries
Reviewed by the Faculty of Harvard Medical School


Minding Your Mind Minding Your Mind
 

Autism and Older Fathers


November 16, 2013

By Michael Craig Miller M.D.

Harvard Medical School


Older men may have a reason to pause before plunging into biological parenthood. Multiple researchers have found a significant increase in the risk of autism and similar disorders as fathers get older.

What Is Autism?

Autism is a profoundly disabling disorder that starts in early childhood. The key features are:

  • Abnormal social development – little or no eye contact, prefers to be alone
  • Difficulty communicating – impaired language ability, uses gestures or pointing rather than words
  • Unusual behavior – spins objects, doesn't like being cuddled
  • Evidence of strong abilities sometimes in non-verbal areas, such as math or music
  • Older people with autism may have some ability to interact with people, but about two-thirds are mentally retarded and most cannot live on their own

Unfortunately, the incidence of this illness appears to be on the rise. Some experts think autism is diagnosed more often simply because more people are aware of it. But that's probably not the whole explanation.

Genetic factors almost certainly play a big role in understanding what causes autism. So researchers are eager to discover anything that might be responsible for increasing a person's genetic vulnerability for the illness, such as having parents who are 40 or older.

The risk is smallest for children of fathers younger than 20 and greatest for children of fathers older than 50. Men in their 50s, for example, are more than twice as likely to have an autistic child as a man in his 20s. Some research shows the multiple to be as much as 6 times the risk. This relationship holds even after researchers adjust the results for the year of the person's birth, their socioeconomic status, or the mother's age.

Health care professionals have long known that as parents age, the risk of giving birth to a child with certain illnesses goes up. Older mothers, for example, are more likely to have a child with Down syndrome. In recent years, studies have also revealed a link between aging fathers and schizophrenia.

Convincing Evidence

Two of the largest studies of this phenomenon have been conducted in Israel and Sweden.

The Israeli study, published in 2006, took advantage of the extraordinarily complete health records of over 300,000 Israeli men and women. They underwent a complete health assessment when they were 17-year olds, prior to entering military service. Using this database, researchers were able to determine the incidence of autism in the population. The researchers had access to intellectual, medical and psychiatric evaluations of almost all Israeli boys and three-quarters of girls. (Their identities were kept secret, however.) For most individuals, the father's age at birth was known.

Although boys were more likely to develop autism than girls, the risk for girls also increased as fathers got older. When fathers were young, about 1 in 6 children with autism were girls. After fathers passed the 40 year-old mark, the proportion of girls with autism rose to about 1 in 3. This suggests that the genetic factors in play for offspring of older fathers are different from those for offspring of younger fathers.

The Swedish study was published in 2011. These researchers found all the autism cases occurring in Sweden over a 10-year period. They accounted for other potential influences, such as the mother’s age and documented risk factors for autism. They found, similarly, that risk of autism increased as fathers got older.

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What Causes These Genetic Errors?

All children inherit genetic material in equal amounts from both parents. In the case of autism, scientists think that the genetic material in the sperm of these older fathers has somehow become altered in harmful ways. These flaws make the child more vulnerable to developing the disease.

According to one theory, mutations (changes) are more likely to develop as men get older. Germ cells give rise to sperm throughout a man's life. These cells make copies of themselves and after several decades, the germ cells are copies of copies of copies. In a 20-year old man, sperm have undergone about 150 divisions. By the time a man is 50, his sperm cells have divided more than 800 times.

A second theory suggests that the offending genes passed down by older men are not properly marked or "imprinted." Accurate marking — which establishes whether a gene is from the father or the mother — determines if it will be active or not. If there is an error, the gene may function abnormally.

A third idea is that some of the more common mutations in sperm cells may appear because those sperm cells divide more rapidly than normal cells. These cells become an over-represented group and so have been labeled "selfish."

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Should Older Men Stop Fathering Babies?

The increased risk of passing on any genetic vulnerability to a child is significant when you are older. When it comes to autism, however, the numbers are sobering. A man younger than 30 has no more than a 1 in 1,000 chance of fathering a child with autism. But the risk bumps up to approximately 3 in 1,000 for a man in his 40s and 5 in 1,000 above age 50. If a father in his fifties has a son, the risk of autism may approach 1 in 100.

This line of study has important implications for what causes autism, but it also has limitations: 

  • It's possible that autistic traits arise as fathers age, but are passed on because they are part of the fathers' genetic make-up all along.
     
  • Maybe people with autistic traits are more likely to become fathers later in life, slanting the data.
     
  • Older fathers could pass along genes for other psychiatric disorders that have traits that look like autism.
     
  • The researchers do not always have access to information about the child's birth environment or development.

Medical technology and general improvements in health have made life much more enjoyable for people in middle to late life. Maybe 50 is the new 30 when it comes to some aspects of aging. But a healthy and active lifestyle does not make 50-year-old sperm the new 30-year-old sperm.

Michael Craig Miller, M.D. is Editor in Chief of the Harvard Mental Health Letter. He is also associate physician at Beth Israel Deaconess Medical Center and assistant professor at Harvard Medical School. He has been practicing psychiatry for more than 25 years and teaches in the Harvard Longwood Psychiatry Residency Program.

 

 

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