Alcoholism, addiction, anxiety and genes

Alcoholism, addiction, anxiety and genes

Posted: Wednesday, September 19, 2012 5:00 pm

The American Medical Association defines alcoholism as “a primary, chronic disease with genetic, psychosocial and environmental factors influencing its development and manifestations.”  
Studies of adoptive children reared apart from birth families with no knowledge of their biological relatives make a clear case for a genetic component to alcoholism. Growing up with alcoholic relatives also increases one’s risk, but here the challenge is to distinguish between genetic and environment factors. 
Chronic consumption of alcohol does eventually create real biochemical changes in the brain, especially for a genetically vulnerable individual. But far more people have a tendency toward addiction than there are alcoholics.  
Alcoholism is just one very deadly form of addiction that is responsible for 4 percent of deaths annually. 
Ten years ago I learned plenty about addiction when I joined a small group at my church in San Diego as a new Christian. Rather than being a “generic” women’s Bible study, as I had originally thought, the group turned out to be an Overcomers weekly meeting. (http://bit.ly/POwhX1). 
Over my several years in that group, I learned that I had many false ideas about substance abuse and addiction. Many of the attendees were highly successful people with very large incomes — not sloppy street drunks.     
Substance abusers deal with their addictive tendencies in obviously destructive ways, but others may use food or workaholism (the list goes on) to produce the sense of calm and false control that others may use alcohol to achieve. 
The transition to genuine alcohol addiction is thought to require a biochemical change in a part of the brain called the central nucleus of the amygdala. The pleasant feelings derived from having a single drink to relax morph to outright discomfort and agitation if alcohol is not present in one’s bloodstream.
There has never been a single gene found to cause alcohol dependency. But there have been studies that link certain DNA variations for certain population groups to alcoholism. The studies are often small and not always reproducible. 
However, there are several SNPs (single-point DNA variations) with very strong links to alcoholism. These SNPs do not capture all the variability, and hence do not even come close to predicting who will become an alcoholic, but they are indeed a validated part of the genetic puzzle.
Some of these SNPs fall in or near genes  that impact the reward pathway, others are in genes that impact how the body metabolizes alcohol, turning it from a toxin to a high calorie (and rather unhealthy) food. Other SNPs fall in genes that impact how neurotransmitters work in the brain. 
There is also an environmental factor. Some people just handle stress better; some people are better at self-soothing without drugs, tobacco, etc. Some families have a cultural heritage where alcohol consumption is not associated with getting drunk but rather special holiday dinners with age-appropriate dilutions and single servings of alcohol, even for the children.
23andme, my direct-to-consumer (DTC) genetic testing company, at present reports on four SNPs associated with alcohol dependence. Some of those studies only included men or Asians. And, honestly, these are not the SNPs with the strongest associations, in my scientific opinion.
One very important SNP, commonly found in Asians but rare for Europeans and Africans, makes the whole process of metabolizing alcohol slow and unpleasant. SNP rs1229984 is found in the gene, ADH1B, which is part of the alcohol dehydrogenase enzyme pathway (which detoxifies alcohol). 23andme does not test for this SNP. (http://1.usa.gov/UgJqsK)
People with even one of the (A) versions, for the ADH1B SNP rs1229984, are more protected from becoming alcoholics because they just feel lousy when they drink much. They are just too slow at detoxification. (http://bit.ly/Rn2ZRh)
A study published this month related the hunger hormone ghrelin to the brain cells involved in alcoholism. (http://bit.ly/Sn2CAA) The paper clarified the relationship between ghrelin and alcohol in the brain’s central nucleus of the amygdala. 
Alcoholics have higher levels of circulating ghrelin than do non-alcoholics; and higher ghrelin levels appear to increase cravings for alcohol. There is a hope that blocking ghrelin might destroy the addiction to alcohol. (http://1.usa.gov/PvRanN)
One of the few confirmed pairs of SNPs strongly associated with alcohol dependency is also associated with impulsivity and anxiety. These two SNPs are both found in the gene GABRA2. 
GABRA2 is a receptor for the most important calming neurotransmitter in the brain, GABA. Think of GABRA2 as a key that unlocks GABA calming effects in the brain. The effect is in both genders, but it is especially strong in women. (http://1.usa.gov/OWtt7d). 
“G” is the risk allele for both of the GABRA2 SNPs: rs279858 and rs279826. I am (GG) for rs279858 and (GG) for rs279826. Alcoholism was never my issue; rather, I specialized in anxiety. 
My problem with being a GG/GG haplotype for GABRA2 is that I did not know any other way to experience life. DTC genetic testing can help provide scientific evidence to face our genetic “demons.”
Editor’s note: Nancy@Nancy MillerLatimer.com has worked in scientific research and development for 27 years. She blogs at NeuronalBeauty.BlogSpot.com
Published in The Messenger 9.19.12

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