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A mother's age is often considered a genetic risk factor for offspring, but research is now pointing the finger at fathers, too—particularly when it comes to the mental health of their progeny. Males may have the advantage of lifelong fertility, but as they grow older, the rate of genetic mutations passed on via their sperm cells increases significantly—putting their children at increased risk for psychiatric disorders, especially autism and schizophrenia. Two recent studies support this link at least associatively, but experts remain uncertain if age is the cause of these problems.
The Malaysian Mental Health Survey (MMHS) results, which were published online in March 2011, for instance, revealed that people with older parents as well as those whose fathers were at least 11 years older than their mothers, were at increased risk for certain mental health disorders, including anxiety, depression, obsessive-compulsive disorder and phobias. Offspring whose fathers were 19 or younger when the child was born had just a 9 percent prevalence of mental health disorders. Regardless of paternal age, however, if the father was 11 years or older than the mother, that rate jumped to 24 percent. The greatest risk of mental health disorders—42 percent—was seen in the children of fathers aged 50 and older, with wives at least 11 years younger than their husbands.
The link between paternal age and increased risk of mental illness has long been recognized by practitioners, but researchers are beginning to unravel more details: "We have known that the children of older men have higher susceptibility to sporadic disease since the 1970s, but there has been an explosion of research in this area," says Dolores Malaspina, a professor of psychiatry and environmental medicine at New York University and a leader in the field of paternal age-related schizophrenia (PARS).
Sperm gone bad?
Some researchers disagree about whether the connection between paternal age is purely based on internal genomic mechanisms related to the aging process, aka "sperm gone bad," or whether environmental and epigenetic factors also affect outcomes.
"The links between a father's age and mental outcomes is multifactorial. You have to take into consideration epigenetic, psychosocial and biological factors," says John McGrath, a professor of psychiatry of the Queensland Brain Institute at the University of Queensland in Australia.
The epigenetic approach is based on the theory that accumulated exposure to environmental toxins over time causes genetic expression alterations that are passed on to later generations and lead to disease in the children later in life. For example, children of Vietnam War veterans exposed to the herbicide agent orange have an increased risk for spina bifida due to epigenetic changes. And drinking and smoking can have epigenetic effects in offspring.
"We do know that there are operating mechanisms whereby paternal experience over a man's lifetime can shape the metabolic pathways of his children," Malaspina says. The question is whether these changes affect the long-term mental health of older men's children.
Likewise, a psychosocial approach focuses on external factors that might contribute to the expression of certain genes. "Delayed paternity does increase the risk of mental disorders, but genetic mutations may not be causative," MMSE researcher Kavitha Subramaniam said in a prepared statement. "They may behave more like susceptibility factors, so that children of older fathers may overreact and show phenotypic expression of certain diseases when they face environmental stimuli. Whereas those with no genetic liability may not develop mental health disorders."