Addiction to alcohol is associated with the brain’s reward system, which reinforces behaviors that feel good — like drinking — by releasing neurotransmitters such as dopamine and endorphins. With prolonged alcohol consumption, a person’s brain can gradually adapt to the point that excessive amounts of drinking are required in order to produce the same pleasure response, and alcoholism results.

That means genetic factors that influence the biochemistry of the reward pathway, as well as environmental factors that encourage alcohol consumption (such as peer pressure and stress) can increase a person’s alcoholism risk.

Researchers have long suspected that a combination of genetic and environmental causes can act together, increasing alcoholism risk more than either acting alone. But so far little evidence has been found for such an effect.

A new paper to be published in the December issue of Alcoholism: Clinical and Experimental Research has found evidence for a synergistic effect between a genetic variation and level of education in a study of 700 Mexican-Americans. The prevalence of alcoholism among Mexican-Americans is relatively high; Mexican-American men report past heavy drinking at three times the rate of men belonging to other ethnicities.

The researchers, Yanlei Du and Yu-Jui Yvonne Wan of the University of Kansas Medical Center, measured three genetic variants associated with the function of chemicals involved in the brain’s reward system. They also looked at marital status and education level in the study participants.

The study found that of the three genetic variants, two were associated with severe alcoholism (defined by consuming more than 35 drinks per day).

o Having two copies of the A version at the SNP rs1799971, which is located on the opioid receptor gene OPRM1, increased the odds of severe alcoholism 2.16 times.
o Having two copies of a variant in the DRD2 gene, which affects the structure of a receptor for the neurotransmitter dopamine, increased the risk of severe alcoholism 1.85 times.

(23andMe customers can see their data for rs1799971 and rs1799732, which is diagnostic of the DRD2 variant, using the Browse Raw Data feature. For rs1799732, a result of II indicates the riskier variant. SNP rs1799971 has previously been associated with the need for morphine as pain relief after surgery as well as sensitivity to social rejection.)

Of the two environmental factors, only education level had an effect. Those with less than 12 years of education had 1.97 times the odds of severe alcoholism. (Having less than 12 years of education also increased a person’s odds of less-severe alcoholism by about the same amount.)

But when the researchers considered combinations of the three associations, they found that having two A copies of the OPRM1 SNP rs1799971, combined with less than 12 years of education, increased a person’s odds of severe alcoholism 3.3 times.

The researchers suggest that a low education level may magnify the effects of the OPRM1 variant, or that higher education may mask its effects by improving brain function.

However, other factors might be responsible for the effect. For example, it is possible that those who attain an education past high school have other characteristics that make them less likely to become addicted to a substance.

There is no way yet to measure an individual’s vulnerability to alcohol addiction, and the complex interaction between genetics, education and other environmental factors must be further studied to clarify the causes of alcoholism in this and other ethnicities.

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It’s no accident that we often refer to rejection or insult as a slap in the face — research shows the same brain signaling pathways are involved in both physical and emotional pain.

And morphine, a drug well known for its ability to dull physical pain, also reduces separation-induced emotional distress in monkeys, dogs, guinea pigs, rats and chickens.  This is thought to depend on changes in signaling through a morphine receptor called MOR (mu-opioid receptor) that is also implicated in emotional pain in humans. Studies have shown that signaling through MOR is reduced when women recall upsetting events like the death of a loved one or the breakup of a romantic relationship.

Given that MOR seems to be at the center of the overlap between physical and emotional pain, researchers from the UCLA Department of Psychology wondered whether a genetic variation in the gene that encodes MOR that is already known to impact sensitivity to physical pain might also affect how thick-skinned a person is.

Baldwin M. Way and colleagues surveyed 122 healthy young adults about their sensitivity to social rejection.  The assessment measured the tendency of study subjects to be fearful that social interactions will result in hurt feelings, criticism and being a burden to others.  The results, published online this week in the Proceedings of the National Academy of Sciences, show that people with one or two Gs at SNP rs1799971 had significantly higher levels of self-reported sensitivity to social rejection than those with an A at both copies.

The G version of rs1799971 has previously been associated with needing more morphine for pain relief after surgery.

(23andMe customers can check their data for rs1799971 using the Browse Raw Data feature.)

A subset of the study participants also had their brains scanned in an fMRI machine while playing an online ball-tossing game.  The subjects thought they were playing with two people, but in reality they were interacting with a pre-set computer program.  The game simulated social rejection by having the subjects’ virtual playmates leave them out of the fun.

Just as in the survey, the G version of rs1799971 was associated with heightened responses to social rejection.  Higher brain activity was recorded in the anterior cingulate cortex and the anterior insula, brain regions associated with the processing of both physical and emotional pain, in people with one or two Gs.

As is usually the case, the results of this study should be considered preliminary until other researchers replicate them. But based on their results, along with previous research, the authors conclude that, “… at multiple biological levels, including the neurochemical, neuroanatomical, and now genetic, feeling hurt physically shares more than just linguistic commonality with feeling hurt socially.”

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