In this issue of Pediatric Research, Vervoot, Delger, and Soubry review what is known about the impact of paternal age at conception and the development of mental disorders in offspring. They focus on six conditions for which paternal age may play a role: autism spectrum disorder, schizophrenia, attention-deficit/hyperactivity disorder, bipolar disorder, obsessive-compulsive disorder, and Tourette syndrome. They also comment on the paucity of epidemiological evidence for a role of paternal age in other psychiatric conditions such as suicidality and substance abuse.

In reviewing prior studies focused on the etiology of the conditions of interest, the authors note the interplay between contributing genetic, epigenetic, and environmental factors in the development of symptomatic disease. Not only do multiple influences contribute to the manifestation of phenotype, they note, but distinct etiological mechanisms likely interact to enhance or suppress disease development. For example, genetic factors contributing to a specific phenotype in the father might predispose him to behavior that results in fathering a child earlier or later in life. Earlier parenting results in childrearing by less mature parents in an often less socioeconomically secure household, resulting in a social environment that could potentially enhance specific phenotypes in the offspring. Thus, paternal genetics directly influences the environment that the child experiences. In contrast, later parenting allows for increased toxic environmental exposures that could impact epigenetic marks on gametes, enhancing or suppressing transmission of the father’s phenotype.

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