The Scicurious Brain

The Scicurious Brain

The Good, Bad, and Weird in Physiology and Neuroscience

Impulsivity, addiction, and your synapses


As you should all know by now, there's WAY more to addiction than simple behaviors. There is physiology underlying those behaviors, and underlying physiology, there are genes. Now, the genes don't MAKE the behavior, and behaviors themselves are not TRAITS (something important for this particular study) which is something we always have to keep in mind. Underlying traits can mix with a wild variety of experiences and other traits to produce an infinity of behaviors. But studies correlating the presence of genes with traits can still tell us something about how some genes can influence someone's tendency toward a particular trait or behavior, and maybe teach us something about the physiology in between.

Stoltenberg et al. "Associations among types of impulsivity, substance use problems and Neurexin-3 polymorphisms" Drug and Alcohol Dependence, 2011.

First, let's talk about addiction and drug abuse. We know something about the mechanisms behind drugs of abuse such as cocaine, amphetamine, or heroin. We have many theories as to why the simple start of drug use may lead to dependence, such as the opponent process theory. But there are fewer ideas and clues as to what makes the transition from drug use to addiction occur in some people and not in others. Obviously not everyone who tries a drug will become an addict, so what makes the difference between those who do a few lines and go on to serve as President, and those who try a drug once or twice and end up hopelessly hooked?

Well, we think part of the answer may lie in your genes.

Now remember, your genes don't MAKE your behavior. Just having a gene "associated" with a particular trait doesn't make that trait universally exist, and certainly doesn't make you, say, a crack addict. It's the interactions between genetics, behaviors, environment, stress, etc, etc, that may make the difference.

But scientists are always looking for new genes associated with particular traits. By finding these genes, they can look at what those genes control, how changes in those genes impact function, and how we might approach those genes with medication to treat disorders like addiction.

In this case, the scientists were looking at a series of genes called neurexins, and at the behavioral trait of impulsivity. First, what do we MEAN by impulsivity? When scientists use the term, we mean a complex of behaviors involving things like failure to inhibit incorrect responses, failures in preparation, premature responding, and lack of persistence, among other things. High levels of impulsivity in humans are associated (not "cause", "associated". Jut because you have the traits doesn't mean you're doomed) with an increased risk of drug and alcohol dependence. So scientists often look at measures of impulsivity associated with specific gene variants, as a way of looking at genetic risk factors for addiction.

Now, on to the neurexins. The neurexins are a set of proteins which act as cell adhesion molecules, gluing cells together. They are particularly important in keeping the synapse stable, the space between two neurons where neurotransmission of cellular signals occurs. Neurexins are some big proteins, and they are coded for by some big GENES. And the bigger the gene (and the less conserved its sequence, which is the case with neurexins), the more likely it is to have lots of little genetic mutations in it, changes in a single nucleotide called single nucleotide polymorphisms, or SNPs. And these single nucleotides can change the way a protein is made, how is functions, or even if it gets made in the first place. Previous studies have shown that changes in neurexins in particular are associated with things like nicotine use, but in this case the scientists wanted to study impulsivity.

They recruited 477 college students, and gave them a battery of impulsivity tests. These are things like: estimating how long it takes for a minute to pass, ratings on an impulsivity scale, measuring how prone people are to boredom, etc. They also asked about tobacco use, alcohol problems, and drug problems. And then they took a sample from the students and genotyped it, looking for SNPs in neurexin.

As other studies have found before, this study found that men and women who has higher impulsivity scores correlated with drug, nicotine, and alcohol use. In this study, in both men and women, specific polymorphisms stood out as being correlated with alcohol dependence (men) and drug use (women), and other specific polymorphisms that correlated with deficits in attention and impulsivity tasks. This may mean that some of these SNPs have trait effects which are sex specific.

The authors conclude that impulsivity and drug and alcohol use are correlated (not particularly new), and that SNPs in neurexin are correlated with impulsivity and drug/alcohol use as well. But two correlations do not make a cause, and the authors know better than to state that these SNPs are predictive for drug use. But they could provide a new area of investigation for the effects of drugs, as well as studies in impulsivity.

This study does leave me with one big question: what are the FUNCTIONS of these polymorphisms? You can't really address this with a human study, but since neurexin has so much to do with synapse integrity, it really makes me wonder what these SNPs are doing. You might be able to conduct an in vitro study to eventually find this out, looking at specific polymorphisms in cell culture and seeing how synapse formation changes. But from there it's a long leap to a whole brain, and then to a whole human and their behaviors. While traits may be ASSOCIATED with certain genetic polymorphisms, function is still far behind.

Measures of impulsivity, but these are genes for synapse formation. Makes me wonder if there's morphological differences involved here. Obviously some of this could be compensated for in development, but it'd be interesting to see how these polymorphisms affect it. Maybe look in vitro in neuronal culture.

The views expressed are those of the author and are not necessarily those of Scientific American.

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