The disease model, in modern medicine, has served us pretty well. Saved a lot of lives, helped us find a bunch of cures, made us pay strangers to poke us… What’s not to like?! In terms of pathophysiology, the model goes like this:
Organ –> Defect –> Symptom. Find the defect, and you’ll have your cause. That’s basically all it takes for something to count as a disease/disorder in medical terms.
Example: The pancreas –> doesn’t produce insulin –> coma. Cause = whatever makes insulin is sleeping on the job, those little islets or whatever. Disease detected! We call it diabetes. Example: Leg –> broke –> femur sticking out through skin, blood and yelling. Disease detected!
But how is this supposed to work with psychiatric disorders, or with addiction? Brain –> ummmm… stupid? –> pouring endless drinks into facehole promptly at 5 pm every day until you’re divorced. Cause = criminally delicious $2 margaritas? Cause = really bad job? Cause = deep, unacknowledged hatred of spouse? Cause = fundamental incontinent failure to reconcile professed moral commitments with actual behavior?
No, this is not simple. No one really faults you if your femur is sticking out of your leg, but no one likes you when you’re puking in her backseat again and/or lying to him over and over again, or being arrested again. We tend to think this behavior is morally bad, and calling it a disease makes it seem like we’re being asked to excuse or overlook the bad behavior of addicts.
Understanding how addiction is a disease or disorder does not necessarily obligate us to condone bad behavior. We can, indeed, keep divorcing and jailing and rejecting those who behave badly, regardless of the causes. However, not understanding the physical mechanisms of addiction means that we will not treat, prevent, or diagnose addiction effectively, thereby creating the conditions for society to suffer the behavior of addicts more than is absolutely necessary. If we can treat addiction effectively by thinking of it as a disease, we should.
It is my contention, following Kevin Macauley, that addiction can be called a defect or disorder of the brain at 5 levels: genes, reward, memory/learning, stress, and then choice.
I’ll start with genetics. It’s probably been awhile since you studied genetics, right? Yeah, maybe we need some reminders. First, I’ll remind you about the difference between genotype and phenotype.
Your genotype is the gene-level set of instructions for building your body. Your phenotype is the actual manifestation of those instructions; the characteristics we can physically observe about you. The same genotype can give rise to all kinds of different phenotypes, and the same phenotype could arise from different genotypes.
Think of it like this: gene-level “instructions” in the building process are set up as an “either-or” instruction. A male-pattern baldness gene would instruct your body thus: Either have male-pattern baldness if you’re male, or don’t if you’re female. In this case, if you were male, the genotype would match the phenotype, and you’d behold your outer George Costanza. Not all conditions and diseases work in such a straightforward manner, however. Some won’t manifest unless several genes are present, some won’t manifest without a particular environmental trigger, and so on.
As far as we can tell, alcoholism is polygenic, meaning it is influenced by many genes (Schuckit 2009). Here is a confusing sentence which I will explain: Heritability of alcoholism, which means the proportion of risk for alcoholism that can be explained by genes, is about 50% (McGue, 1999).
Let’s say you’re told that you have a genetic profile that includes markers for a disease, and that the heritability of that disease is about 50%, what the hell does that mean? Does it mean you have a 50% higher chance of getting it than everyone else? No, not really. Does it mean people with my genes get it 50% more than everyone else? No, not really. It doesn’t really explain the “chances” that you, as an individual, will get the disease at all.
SO WHAT THE HELL USE IS IT, JEN?! TELL ME WHEN I’M GONNA DIEEEE
The two most important things to know: when we talk about the heritability of disease, we are talking on a population level, NOT an individual level. Also, it makes more sense if you know that the number we use for heritability is a proportion. If I say a disease has 0 heritability, this means genes don’t account for any differences among phenotypes. If I say its heritability is 1, this means genes are the only explanation for why some people get it and others don’t.
All right, then: when we say alcoholism has a heritability of 50%, that means… what? It does NOT mean that 50% of MY alcoholism can be explained by genes and the other half by environment. It does NOT mean that 50% of people with my genetic profile will become alcoholics. It’s about populations, so it means that genes explain about 50% of the differences among all people when it comes to whether or not they will become alcoholics.
It’s clear we haven’t found “The Gene,” right? Why don’t we just keep looking for that one culprit gene that will give us a 1-1 association for alcoholism? Well, it’s not that simple, you jerk. Shut up and learn.
Organs like kidneys and livers are all pretty much homogenous on a cellular level. All the little liver cells in one liver are mostly the same, doing the same stuff as one another, hanging out and having the same conversations all the time (“Awesome, bro”). There are only so many things they can do. Identifying a genetic component of a disease is simpler when there are only a few kinds of cellular activities to work with.
But when it comes to diseases affecting the brain, it gets more difficult. It’s not just that every brain is a little different from every other brain. It’s that lots of your brain cells are different from one another, not to mention all the unique ways they connect, react to novel environments, and so on. Psychiatric diseases, then, are quite difficult to talk about in terms of genetics, because there is rarely a one-to-one correlation between genotype and phenotype.
It doesn’t help genetic research into alcoholism, then, just to look at a set of behaviors and try to work backward to a definitive culprit gene. What does seem to help is to look at endophenotypes. This is a characteristic, something observable or measurable, that shows up in people with a particular disease more often than not. It’s something that may manifest in a lot of folks whether they have a disease or not, but it is associated with a disease, and seems to show up in family members of people with that disease at a higher rate than in the rest of the population. Skinny jeans are kind of like an endophenotype for hipsterism: we know hipsters wear them, so you’re probably a hipster if you wear them, but you don’t necessarily have to be a hipster to manifest the skinny jeans.
For instance, a deficit in identifying emotions in others’ facial expressions is an endophenotype associated with bipolar disorder (Rosen and Rich, 2010). Just because you have the deficit doesn’t mean you have bipolar disorder, but people with bipolar disorder usually have the deficit. So, we say the deficit predicts a high risk for bipolar disorder. Knowing about endophenotypes may help with early diagnosis, prevention, or treatment.
There are at least four endophenotypes associated with alcoholism; the latter two are associated with addiction in general:
1) The skin-flushing response to alcohol predicts a lower risk for alcohol abuse and dependence (Li, 2000). This may be because the redness clashes with your outfits and you don’t like how it looks, of course, but it’s also a marker for the way you process alcohol. You probably process it in such a way that you’re not likely to drink a lot.
2) A low level of response to alcohol predicts higher risk for alcohol abuse. If you’re a low responder, you’ll drink more to get the desired effects (Schuckit, 2002). If you’re a high responder, on the other hand, you’re probably lit after half a wine cooler, so you’re likely to drink less. **edit: further, if you’re a low responder with a particular EEG pattern of alpha waves that is associated with anxiety, you may be more likely to abuse alcohol. Alcohol increases the proportion of slow alpha waves, so alcohol may actually reduce anxiety by markedly affecting alpha wave activity in people with this EEG pattern (See Schuckit 2002, above), making them maybe want to drink more.
3) “Sensation-seeking” or impulsivity and disinhibition. This doesn’t only predict high risk of alcoholism; it’s associated with a lot of other disorders, too. A marked tendency toward impulsive decision-making, or a tendency to prefer immediate over delayed gratification—these are endophenotypical markers for increased risk of addiction in general.
4) Finally, there’s the fact that addiction is “comorbid” with a whole bunch of other psychiatric disorders. Comorbid describes a situation in which a person has two or more diseases/disorders at the same time. Alcoholism is often comorbid with bipolar disorder, schizophrenia, and anxiety or depression disorders. It’s not that one condition causes the other. It’s that they seem to arise together a whole lot. In other words, you can have bipolar disorder and not be an alcoholic. You can be an alcoholic and not have bipolar disorder. But a significantly higher number of folks with bipolar disorder also have alcoholism. This suggests, perhaps, that whatever genetic factor makes you susceptible to bipolar disorder also makes you susceptible to alcoholism. The same goes for the other psychiatric disorders listed. So, alcoholism seems to be linked to the same genes that operate on several psychiatric disorders (Schuckit, 2009: This article is a detailed overview of genetic influences in alcoholism).
So, what does all of this tell us about addiction?
For one, it tells us that there really is a difference in how drugs feel to addicts as opposed to non-addicts, and that this is a difference absolutely void of moral content. There are vulnerabilities present for the addict that she isn’t aware of, doesn’t see functioning, can’t know about before she takes that first drink or pops that first pill. Two 14-year-olds can try their very first beer at the very same time, and one may never touch it again, while the other may have a profoundly different response simply due to genes. Cue dramatic kettledrums signifying doom for the latter hapless adolescent.
That doesn’t help explain why people keep on drinking or doing their drugs despite obvious negative consequences though, does it? Not everyone who’s a low responder, for instance, becomes an alcoholic. We need to understand why some people become addicted and some people don’t even when they have similar genotypes.
Next, we’ll take a look at how addiction manifests as a disorder of the hedonic system, that part of the brain’s systems which governs reward and pleasure. Go here for Part 3.
One thought on “#2: The Disease Model, Genetic Vulnerability, and the Complex Tyranny of your Grandmother’s Taste in Men.”
I have found that I do not like the fuzzy feeling that pain pills cause.