A few years ago, I attended a talk by Nora Volkow, the head of the National Institute on Drug Abuse.
I studied drug addiction as part of my graduate education, but before listening to her speak, I had not given much thought to addiction outside of textbooks and journal articles relevant to my research.
Drugs of abuse hijack the dopamine system. Maybe you’ve heard that before. I had. But addiction is more than just dopamine. Addiction impacts the entire brain, structurally and chemically.
It is not a character flaw; it is a chronic disease.
Relapse rates are on par with more socially acceptable chronic diseases like diabetes or heart disease.
Drug addiction is heritable.
And it is established easiest in developing brains.
Finding the needle in the haystack with endophenotypes
Addiction is a heritable disease—genetic research estimates between 40 and 60 percent—and is also linked to personality types, which are also heritable. Traditional molecular genetic research, which attempts to link genes to clinical outcomes (i.e. disease), has yet to identify genes specifically associated with addiction.
Leading addiction researchers, including Volkow, encourage the study of endophenotypes, where behavioral traits associated with diseases are used to help identify clinically relevant genes. Studying genes associated with behavioral traits that are themselves linked to diseases should be more successful than directly linking a gene to the disease.
Personality type is a behavioral trait used to identify endophenotypes associated with addiction. Personalities with more neurotic and negative emotional tendencies (labeled NEM/N) are associated with addiction and other mental health disorders that often co-occur with drug addiction, like depression and anxiety. NEM/N personalities are also associated with variations in the serotonin transporter gene, which is one of the most studied genes in all neuroscience.
Though the NEM/N personality is associated with addiction and serotonin genes are associated with NEM/N personalities, serotonin genes have not yet been strongly linked to drug addiction! Volkow and her colleagues use this example to argue for “the lack of utility of directly connecting genes and clinical phenotypes” and to push for using behavior to identify biological markers of addiction.
If the important gene is the needle and the human genome is the haystack, studying endophenotypes facilities finding that needle by reducing the size of the haystack. Identifying genes associated with addiction is important because of potential treatment therapies.
The establishment of addiction and the vulnerability of growing up
Drug addiction is most likely to take root before the brain finishes developing, which for humans is the mid-20s or maybe even into the early 30s. Rats exposed to nicotine as adolescents self-administer more nicotine than rats first exposed as adults. The vulnerability of adolescence to drug addiction is true of humans too; exposure to drugs during adolescence increases the likelihood of addiction. And adolescence is when most people experiment with drugs.
Addiction is a developmental disease that usually begins in adolescence.
Last week, a study was published that looked at how marijuana use affects the human brain. Structural changes in two brain regions were identified. These two regions, the nucleus accumbens and amygdala, contribute to computations underlying reward processing, decision-making, and emotions and are affected in addiction and mental health.
In marijuana users, the nucleus accumbens and amygdala differed in size compared to nonsmoking controls and also showed denser gray matter. Denser gray matter is one of the ways addictive drugs are known to physically change the brain; they create additional connections between neurons.
The 20 participants in this study ranged in age from 18 to 25 years; all likely still had developing brains, even though they are legal adults. Research suggests that roughly a quarter of the marijuana using participants (5 or 6 people) could end up suffering from addiction (see Figure).
In an interview, senior author Hans Breieter said the nucleus accumbens and amygdala are “a part of the brain you do not want to mess around with.”
Breiter is right but understates the implications of this study.
There are no brain areas that are okay to mess around with.
Also, drugs of abuse—legal and illegal and maybe-should-be-legal—are probably not the only substances that alter the brain. Everything that goes into our bodies affects our brains somehow, even food.
Food addiction is complicated because unlike drugs of abuse, we have to consume food to survive. (Food addiction deserves its own blog post, so stay tuned.) However, it would be very interesting to see if over-consumption of sugar, an addictive substance, is associated with physical brain changes linked to drug use.