Why do some people get addicted while others remain immune to the lure of drugs? Neuroscientists have been studying this question for years, asking whether the difference arises from particular variations in brain structure. But until now the research has not been clear on whether the brain changes seen in addiction are a cause or the result of excessive drug use.
A new study of siblings published Thursday in Science suggests that at least some of the brain differences come first. The study compared cognitive function and brain structure of 47 people with addiction, with 49 of their nonaddicted siblings and 50 healthy unrelated and drug-free volunteers.
The addicted people had long histories of substance misuse: on average, they had been using stimulants — mostly cocaine, but also some amphetamines — for 16 years. Slightly more than half were also addicted to heroin or prescription painkillers, and a quarter had alcoholism as well. The siblings, in contrast, had minimal exposure to drugs.
All participants were tested on one predictor of addiction: the ability to control one’s own impulses. This is the ability that most of us practice on an hourly basis: It stops you from spilling a friend’s juicy secret, lets you resist a second trip to the dessert bar and keeps you from telling your boss what you really think of her.
In the lab, one type of impulse control is tested using something called a stop-signal task, an exercise in which you are asked to respond quickly and repeatedly one way — for example, by pressing a button in response to an on-screen prompt — then are suddenly required to resist that behavior.
When researchers tested participants on the stop-signal task, they were surprised to find that both the addicted people and their siblings showed significantly reduced performance, compared with controls. Typically, scientists are used to seeing these kinds of deficits only in those who are addicted. The finding suggests that poor impulse control is not a result of drug use, but something that arises from an inborn predisposition.
Brain scans also showed that siblings had similar abnormalities in the connections between their inferior frontal gyrus, an area of the brain involved with self-control, and other regions that are critical for inhibiting impulses. In both addicted people and their siblings, these connections were weaker than in control participants; the more feeble the connections, the worse they did on the stop-signal task.
“The inferior frontal gyrus is really one of the main ‘brakes’ of our brain,” says Dr. Nora Volkow, director of the National Institute on Drug Abuse, who wrote a commentary accompanying the study in Science. “[Drug users and their siblings] have less connections that are linking the rest of brain with the inferior frontal gyrus [and other key regions] that form a network that allows you to inhibit responses.”
Interestingly, the authors note, these connectivity problems are similar to those seen in the brains of teenagers, a group that is characterized by impulsive behavior. It is almost as if the brains of addicts are less mature. “They look as if they are at an earlier developmental [stage],” says Volkow.
Perhaps that helps explain why some addiction wanes with age. Studies find that most people who struggle with alcohol and other drugs in their 20s “are out” of their problems by their 30s, typically without treatment. Perhaps those who do not have brains that take longer to grow up.
But the big question, as Volkow points out, is why the siblings in the current study ended up following such different paths when they shared the same vulnerabilities to addiction. Why did one become addicted, but not the other?
Additional results from the brain scans may provide intriguing hints at an explanation. For instance, people with addiction — but not their siblings — showed decreased activity in their medial orbitofrontal cortex (OFC). “That area is crucial in terms of enabling you to have flexibility and to shift your behavior as a function of changes in [the] environment,” says Volkow.
She offers an example: if a candy machine swallows your change without releasing the goods, normal people will stop putting money in (though some might kick it a few times). People with damage to the OFC, however, will keep putting money in and expecting treats to come out.
“In addicted people, we consistently see decreased activity in this area of the OFC,” says Volkow, noting that studies have looked at people using cocaine, methamphetamine, marijuana and alcohol. “That is likely to explain why they repeat and repeat and repeat drug-taking even when they tell you that it doesn’t make them feel good anymore.” (Damage to the OFC is also seen in obsessive-compulsive disorder, another condition in which people repeat behaviors and thoughts that they know are useless or even self-destructive, but have difficulty controlling.) High levels of activity in the OFC, in contrast, are linked with positive emotions and a sunnier outlook.
The current study could not determine whether pre-existing OFC deficits may have led people to try to self-medicate with drugs, thereby leading to addiction, or whether the drugs resulted in damage to the OFC. When the researchers looked at the early lives of the sibling pairs, they found all the same risk factors: both the addicts and their siblings had led equal amounts of trauma in childhood, far more than the control group. “We really looked at their childhoods,” says Karen Ersche, lead author of the study and group leader for human addiction research at the University of Cambridge in England. “There was a lot of domestic violence, there was sexual abuse — but both [groups] had that.”
Another brain area in which drug addicts and siblings differed was the precuneus. “Your awareness of yourself is mediated by the precuneus — and the insula — and disruptions in how these areas work can mean greater sensitivity to states of deprivation [and] much less tolerance for craving, hunger or frustration,” Volkow says.
In other words, while both drug-addicted people and their siblings showed the same problems with impulsiveness, the siblings may have been less likely to experience craving or to have problems refraining from habitual behavior. The siblings appeared to have inherited a type of protective resilience, perhaps via an easier temperament. “The siblings may have tried drugs, but they never developed the habit,” says Ersche. An earlier study in the same group showed another difference: the addicted people were more likely to seek intense stimulation, compared with their siblings, which could have made drugs more desirable and more enjoyable for them.
The current study is one of the few that has allowed researchers to distinguish between brain changes that predispose people to addiction, and those that may be the result of heavy drug use. The brain changes shared by drug addicts and their siblings in the study could not have been caused by addiction, but they may have helped lead to it. “If you think about how stigmatized addiction is,” Ersche says, “it helps to know that it’s related to the brain and not a failure of character or lifestyle choice. And we need treatments that include [understanding and treating] the brain.”
Still, while genes can influence behavior, they don’t determine it. Despite the fact that they shared certain brain-related vulnerabilities, the siblings of drug addicts had managed to remain drug-free — and chances are, they had plenty of opportunity to become addicted. “They have reasons to self-medicate but they don’t, and I’d like to know how they’ve done it,” says Ersche. “They may actually be able to help people recover if they have strategies to apply to [living with a susceptible] brain and upbringing.”