Epigenetics update: DNA of the dry drunk

“To Alcohol – the cause of and solution to all of life’s problems.”

This post is about epigenetics in alcoholics who are weird even after they’ve stopped drinking.

First, before everyone shoots out our tires, yes, we totally believe alcohol dependence is biological, and not some kind of  metaphysical “character” defect of “lack of willpower” or other such judgmental nonsense. We don’t judge the addictions of others, any more than we judge anything else biological. But that doesn’t stop us from complaining about it. Second, all the current and ex- alcoholics in our orbit think like aliens visiting earth on an empty stomach.  Turns out, not surprisingly, epigenetics seems to have something to do with it.

The abstract that initially caught our eye:  Zhang H, Herman AI, Kranzler HR, Anton RF, Zhao H, Zheng W, Gelernter J. Array-Based Profiling of DNA Methylation Changes Associated with Alcohol Dependence. Alcohol Clin Exp Res. 2012 Aug 24. doi: 10.1111/j.1530-0277.2012.01928.x. [Epub ahead of print] PubMed PMID: 22924764.

(Our previous post: Unhealthy Brains Have Potted Plant Defenses discussing a paper that points to genetic elements jumping around out of control in alcohol addiction; also see our addiction category, and a site-search for “epigenetics.”)

We’re thinking of a particular former alcoholic we knew — once a hard charging, Type A — high-functioning-until-he-flamed-out white guy with all the privileges. In his younger days, he was brilliant and charming — ivy-educated, a former elite trained military person, and all around swell guy in a position of power. Then came the hiding vodka bottles in the toilet tank, the firings, the divorces, the alienation of his children, colleagues, and just about everyone except his similarly dysfunctional siblings and some acquaintances who didn’t know and still found him amusing. The inevitable crash was a fiery and loud one. He’s dead now. We all predicted an early death. No one was surprised particularly, except that he apparently died in his sleep instead of some more dramatic way.

He 28-day rehabbed a 5-6 times. The 28 day detox stint,while long enough for detox-wash-rinse-repeat, wasn’t nearly long enough to make any lasting changes. It was more like reform school, a place to learn new tricks.  He knew he was smarter than everyone there, and so dug up dirt to get rehab professionals fired, had affairs, conspired with other 12-steppers, and all of it. The worst. The kind you see on Celebrity Rehab and think “even when this guy gets sober, he’ll still be an idiot.”  Ask him why he bothered with rehab (it was only court ordered once), and he frankly didn’t know. He spun tales of his self-sabotage with short spurts of Machiavellian glee, but mostly with a look on his face like, “I hear my own words and even I don’t know why I thought that was a good idea at the time.”

After a heart attack or two, and “going under the Black and Decker,”  he was a totally sober 12-stepper.  But he was damaged, you could tell from looking at him.

We don’t know why we never noticed it before, but from a particular angle he had that flat-mid-face of fetal alcohol.  Could have been our confirmation bias, but it would make sense considering he said his socialite mother was usually on the couch passed out by the time he got home from school. (He said, but who knows for sure – the inadequately rehabbed are pros at externalizing blame to bank some pity points.)

And, in sobriety, he walked around looking perpetually surprised. Why? Personal interaction required social trigonometry to figure out how to be “normal.” His natural impulses had skewed toward negative attributional bias and aggressive hostility. And paranoia. Neutral facial expressions were threats, people were out to get him, and his once reliable brain power was stuck in first.

And the hostile downward spiral began. He helped an artist friend move her gallery, and then sued her for a percent of her art work, legal theory unknown. He had a friend who worked for a luxury goods company with an employee discount — and so bought the purses and wallets at the discount and sold as “NWT” at a mark-up on E-bay — in total violation of the employee agreement. The luxury goods corporation promptly sued for selling fake goods. The goods were real, but one could argue that there was not only breach of the employee agreement not to do such thing, but also civil conspiracy for hatching the plan. He sued an acquaintance of your loyal bloggist for giving him some professional contract work, and then claiming that he was ripped off. (He actually was on that one, the acquaintance turned out to be a psychopath, too. That was interesting – like watching a fight in the reptile cages.) But basically he pissed off everyone who tried to help him out.  You can see the pattern – he played both the victim and the victimizer.

In the big scheme of things, all of his efforts to game the system, to be top dog, were pointless.

And now we have research on the DNA of the dry drunk (our characterization, not that of the authors). The study reports that  among the genes shut off are a dopamine receptor,DRD4, and a serotonin-related promoter, HTR3A, encoding a serotonin receptor.

Addiction can be associated with the dopamine receptor allelic variant, dopamine receptor 4, having 7+ tandem repeats, the one thought to encode the dopamine receptor that doesn’t hang on to dopamine all that tightly, and so you need more dopamine to get a rush (to oversimplify). This allele is also associated with disinhibition – acting crazy, including binge-alcohol use (sometimes). We guess that shutting down this dopamine receptor gives alcoholics even more of a need to seek out dopaminergic thrill rides, and act even crazier.  Dry drunks must just be dopamine-deprived. (Is this why they get the DTs? Is that like a Parkinsonian tremors associated with dopamine deficiency?)

As to serotonin, normally drinking should up your serotonin production and make you feel good in that serotoniny way. A recent report demonstrates when you squirt alcohol directly on human neurons in a Petri dish they not only ramp up serotonin receptor production, but also decrease histone inhibition of serotonin receptor DNA transcription (here).  Yet, for alcoholics, drinking apparently results in epigenetic changes that reduce serotonin receptor production.  We’re guessing that is the angry-dry-drunk stage.

We suppose the useful information is this: drink a little, but not a lot — that gets the serotonin going, but too much shuts it down.

And, if you are a dry drunk, it really is you, so just settle down and stop bugging people.