Nicotine Use May Heighten Risk of Substance Use and Anxiety-Like Behaviors in Offspring

The report suggests that smoking by fathers could lead to alterations in their offspring. Male offspring may be more susceptible than female offspring.

A new report that documents the intergenerational impacts of nicotine use could pave the way for new insights into how smoking can have long-term health consequences, even beyond those to the smoker himself.

The findings come from animal studies and are preliminary,

The study looked at whether and how nicotine use affects offspring. In findings reported in the journal Molecular Psychiatry, investigators from the University of Pennsylvania, Temple University, and Rutgers University explain that the answer to the first question appears to be “yes.”

Specifically, the study suggests that paternal use of nicotine increases the risk of nicotine use in the sire’s offspring, and that male offspring are also more likely to experience memory deficits and increased anxiety if their father used nicotine. The latter finding was only applicable in male offspring, not in female offspring. The study was based on a rat model.

“We do not know why some of the heritable effects of paternal nicotine-taking are sex-specific,” Heath D. Schmidt, Ph.D., the study’s lead author, told Managed Healthcare Executive. “However, the sex-specific effects that we see on anxiety are consistent with previous preclinical studies.”

Schmidt, a professor of neuroscience and pharmacology at the University of Pennsylvania, said other studies looking at the effects of parents using nicotine, opioids, or cocaine, have also shown that males, but not females, have increased anxiety-like behaviors.

He said a better understanding of these sex-specific effects is an important future research direction.

“Imprinted genes and parent-of-origin effects on gene transcription in the descendant brain could influence sex bias in the brain,” he said.

In the study, Schmidt and colleagues also used an unbiased, genome-wide microarray analysis to see whether they could pinpoint molecular changes associated with these effects on offspring. They found the impacts were linked with a reduction in the expression of Satb2, a transcription factor, in the hippocampi of male offspring. Female offspring had no such reduction in Satb2.

When investigators increased Satb2 expression in the male offspring, they found that the restoration of Satb2 prevented the escalation of nicotine-taking and also restored memory deficits.

Though his study used an animal model, Schmidt said the findings open up interesting questions about the long-term consequences of smoking on humans and their offspring. For one thing, he said the behaviors observed in the study have parallels with common disorders in humans.

“Some of these heritable behavioral responses are consistent with human neurodevelopmental disorders including ADHD [attention deficit hyperactivity disorder] and autism spectrum disorder,” he said.

He said the changes could extend to behavior and addiction.

“There is also some evidence supporting shared epigenetic changes between fathers that smoked cigarettes and their offspring in the expression of genes associated with substance use disorders and behavioral dysfunction,” he said.

“Our findings could be used to increase public awareness of the potential heritable effects of paternal nicotine exposure,” he said.

Another question is whether the remedy seen in the animal study—increasing Satb2—might be applicable to humans. Schmidt said he is unaware of any existing therapy that directly targets Satb2, and he said investigators would still need to find out for sure whether Satb2 is actually altered in the hippocampi of children of smokers.

“If so, it could be a potential target for novel interventions in the offspring of smokers who have cognitive deficits,” he said.