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HOT TOPICS: Alcoholism  Addiction  AA  Cocaine  Heroin

Alcoholism and Genetics: What You Need to Know

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By Jeanene Swanson

05/12/14

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INHERITING EXPERIENCE?

In the mid-1800s, the theory of natural selection replaced the idea initially proposed by biologist Jean-Baptiste Lamarck, who believed that acquired characteristics could be inherited. Now, study after study is showing that by some mechanism, acquired traits—like sensitivity to drug exposure—can, in fact, be passed from parent to offspring. While several well-cited studies have shown epigenetic inheritance of disease, studying transgenerational effects in drug addiction is in its infancy.

Yasmin Hurd, a professor at the Mount Sinai School of Medicine, published a study early this year showing that adolescent rats that were exposed to THC had first-generation (F1) offspring who were, among other telltale behaviors of addiction, more likely to use heroin compulsively. On a molecular level, parental THC exposure was associated with gene expression changes in the cannabinoid, dopamine, and glutamatergic receptors in the dorsal striatum of the F1 offspring—this area of the brain is important for compulsivity and reward-seeking behavior.

“I wasn’t really expecting this significant of an effect,” Hurd says. “We thought that most of the epigenetic things that happened to you are erased, and basically you don’t pass on those epigenetics marks to your children.” Sperm and egg cells are believed to lose most of their acquired epigenetic marks during a “reprogramming” process when the two meet. “Now, we realize that that’s not true, so what are the mechanisms?”   

Hurd’s lab is busy exploring this. Next, she plans to scour the epigenome of the pups, to see what their patterns of marks show. She also plans to see how this might play out in a second generation.

Other groups have found startling proof that past drug-taking behavior affects offspring. In January of 2013, Chris Pierce, a professor at the University of Pennsylvania Perelman School of Medicine, found that male offspring of rats who had been exposed to cocaine showed less addictive behavior toward cocaine. They then measured and found that levels of a certain protein, BDNF, were increased in the medial prefrontal cortex of the male pups.

Fair Vassoler, a co-author who was working in Pierce’s lab at the time, believes that this decreased susceptibility is not that surprising in that it is a protective effect. The study built on their earlier work that showed that in rats exposed to cocaine and then followed by a period of abstinence, levels of BDNF were increased in the prefrontal cortex, the decision-making center of the brain. BDNF, or brain-derived neurotrophic factor, is involved in the health of neurons, “a fertilizer of the brain,” Vassoler says. “This might be a compensatory mechanism,” in that in response to cocaine, the brain makes more BDNF “to prevent rats from taking more.” They hypothesize that the pups of cocaine-using rats have inherited the increased levels of BDNF to protect them from becoming addicts themselves. Females don’t share the protective effect, and Vassoler does not know why. Next steps are seeing how the next generation, F2, responds to cocaine, and if the protective effect is passed on to a third generation.

In a paper from late 2013, Vassoler, then working with Elizabeth Byrnes at Tufts University’s Cummings School of Veterinary Medicine, and her colleagues found that exposing adolescent female rats to cannabinoids enhanced their female pups’ response to morphine. In a most recent paper from April of this year, adolescent females exposed to morphine had male offspring who were more sensitive to morphine.

Considering rates of prescription opioid use and addiction—especially by younger people—Vassoler says the main take-home message of all this research is one of awareness. “Whether you’re male or female, [your behavior] can affect the next generation,” she says. “That’s pretty new, really important. And, it could really help to make people think before they act.”

IS THE DAMAGE REVERSIBLE?

The burning question on many recovering addicts' minds will be, Is there anything I can do to reverse the damage I’ve done before having children? Most interviewed were cautioned about considering epigenetic changes as necessarily bad. And, many of these changes are transient—that is, methyl groups can be tagged on, and they can be tagged off—in response to environmental stimuli. Most importantly, these studies involve rodents; humans are much more complex in their response to stress.

“Some of these changes are reversible,” Harvard’s Sadri-Vakili says, while others are more static. A theory based on environmental enrichment has emerged which says that a stimulating, nurturing environment in recovery can help reverse these changes. Vassoler is a proponent - the last thing she wants is for recovering addicts to believe that they should not have babies. “The work that we’re doing in lab rats is so very far removed from humans,” who are obviously going to live a much more enriched life.

Sadri-Vakili emphasizes getting more exercise, or playing mentally stimulating games like chess, to increase levels of BDNF in the brain. “All these things will help boost BDNF levels,” she says, which is important for synaptic plasticity in improved learning and memory. “It keeps minds plastic, and growing, and healthy.”

Jeanene Swanson is a regular contributor to The Fix. She last wrote about methods of erasing traumas.

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