Older Dads and Greater Risk For Autism, Schizophrenia
Older men are more likely to have children with autism or schizophrenia due to random mutations that increase with age, says a just-published study in the journal Nature. Could these results help to explain the drastically higher rates at which autism is now diagnosed?
In the US, the birthrate of fathers age 40 and over has increased more than 30 percent since 1980. The autism diagnosis rate has increased tenfold. Earlier this year, the Centers For Disease and Control reported that the prevalence rate for autism among American children is now 1 in 88, a 78 percent increase since 2007. Scientists and public health officials have also pointed to changes in the diagnostic criteria for autism spectrum disorders in the Diagnostic and Statistical Manual of Mental Disorders as a factor. With a better understanding of what autism is, doctors and parents have been better able to detect signs of autism in children.
Genetic Mutations and Brain Development
The new study is being hailed as it provides “some of the first solid scientific evidence for a true increase in the condition,” as Dr. Fred Volkmar, director of the Child Study Center at the Yale School of Medicine, says in the New York Times, in contrast to claims (often widely promulgated via the internet) that, for instance, vaccines have caused such a great increase in autism diagnoses that there is now an “autism epidemic.”
Scientists from the the Icelandic firm deCODE Genetics led the new study, in which whole-genome sequences of 78 trios of a mother, father and child, all from Iceland, were analyzed. Families without a history of mental disorders were the focus.
While women are born with a supply of egg cells for their whole lives, sperm cells divide every fifteen days or so and “continual copying inevitably leads to errors, in DNA as in life,” as the New York Times puts it. Fathers therefore pass on more mutations than mothers.
Scientists isolated de novo or spontaneous mutations that were present in a child but not in their father’s or mother’s DNA. The mutations must have occurred spontaneously in the egg, sperm or embryo. As Callaway explains,
Fathers passed on nearly four times as many new mutations as mothers: on average, 55 versus 14. The father’s age also accounted for nearly all of the variation in the number of new mutations in a child’s genome, with the number of new mutations being passed on rising exponentially with paternal age. A 36-year-old will pass on twice as many mutations to his child as a man of 20, and a 70-year-old eight times as many, Stefánsson’s team estimates.
The researchers estimate that an Icelandic child born in 2011 will harbour 70 new mutations, compared with 60 for a child born in 1980; the average age of fatherhood rose from 28 to 33 over that time.
While most of these mutations are harmless, Stefánsson’s team found that some are those associated with autism and schizophrenia.
As Stefánsson notes in the New York Times, it is indeed likely that de novo mutations might play a part in brain development because “at least 50 percent of active genes play a role in neural development, so that random glitches are more likely to affect the brain than other organs, which have less exposure.”
Older Men Pass On More Mutations
Earlier studies have also suggested that children born to older men are at a higher risk of being diagnosed with autism. Other studies have linked increasing maternal age to children born with developmental disorders; older women are at more risk of having a child with chromosomal abnormalities like Down’s Syndrome (and, in a previous generation, women were outright blamed for “causing” a child to become autistic by being emotionally frigid “refrigerator mothers” who failed to bond with their children).
The new study, though, has found that, in cases of developmental and psychiatric problems, most of the genetic risk comes from the sperm, not the egg.
So, Should Older Men Not Have Kids?
In an editorial accompanying the study, Alexey Kondrashov of the University of Michigan’s Department of Ecology and Evolutionary Biology and the Life Sciences Institute, writes that, in some cases, “collecting the sperm of young adult men and cold-storing it for later use could be a wise individual decision.”
Despite this, scientists underscore that the study is not meant to give older men reason to forego having children, as most genetic mutations have no consequences. Mark Daly, a geneticist at Massachusetts General Hospital in Boston, also notes that autism is highly heritable and that “most cases are not caused by a single new mutation — so there must be predisposing factors that are inherited from parents but are distinct from the new mutations occurring in sperm.”
As for my own teenage autistic son, Charlie: While there are no autism spectrum disorder diagnoses in our families, there is a history of mental disorders in both my husband’s and my families. (Indeed, a couple of my relatives seem likely candidates for a diagnosis of Asperger’s Syndrome.) With more individuals diagnosed with ASDs, my main hope that is that greater understanding and awareness can make more programs, accommodations and services available (with adequate funding), so those on the spectrum can lead good lives in communities that support them.
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Photo by Sellers Patton