Research News Update - Fatherhood Matters

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Dolores Malaspina, M.D., NARSAD Young Investigator Grantee, Jay Adam Gingrich, M.D., Ph.D.,  NARSAD Distinguished Investigator Grantee, Eric J. Nestler, M.D., Ph.D.
Drs. Malaspina, Gingrich, and Nestler

A recent New York Times article titled "Why Fathers Really Matter" cites the work of three NARSAD Grant-funded researchers.

The article reports that a recent comprehensive study advances earlier NARSAD Grant-funded research demonstrating a strong influence of paternal age with spontaneous human genetic mutations that can lead to the development of brain and behavior disorders such as autism and schizophrenia. The study quantifies the risk of paternal age for the first time by calculating how many times male reproductive cells divide with age, whereas a woman is born with all the eggs she will ever carry. Each time the male cells copy themselves, mistakes can appear in the mutations.

The new study lends credence to those who have proposed that one of the reasons for the great increase in the number of autism cases over the years is due to the increasing average age of fathers.

More than a decade ago, Dolores Malaspina, M.D., published results of her NARSAD Grant-funded research that showed children born to older men had a significantly higher likelihood of developing schizophrenia. At the time, the findings represented a paradigm shift, demonstrating scientifically for the first time that paternal influence can be linked to the development of brain and behavior disorders.

Two-time NARSAD Young Investigator Grantee, Jay Adam Gingrich, M.D., Ph.D., did further work on animal models started by Dr. Malaspina and found similar results. In his work, older male mice produced offspring showing signs similar to schizophrenia in adulthood. “There was about a six-fold increase in likelihood that one of the ‘abnormal outliers’ [outside the vast majority of normally-developed mice pups in the sample] with cognitive or behavioral handicaps would come from an older father,” he reported.

NARSAD Distinguished Investigator Grantee, Eric J. Nestler, M.D., Ph.D., has recently published work showing that male mice subjected to high levels of stress and having symptoms of depression, anxiety or post-traumatic stress disorder (PTSD) prior to breeding tended to pass along these mental illnesses to their offspring. Dr. Nestler is not sure exactly how the mouse fathers’ trauma communicates itself to their offspring. It may be via sperm, or it may be through some more complicated dance of nature and nurture that involves sperm but also other factors.

While the paradigm continues to shift away from maternal influence being the primary determinant of a child’s mental wellbeing, there remain many questions for further study.

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Please note that researchers cannot give specific recommendations or advice about treatment; diagnosis and treatment are complex and highly individualized processes that require comprehensive face-to- face assessment. Please visit our "Ask an Expert" section to see a list of Q & A with NARSAD Grantees.
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