Wired? In both drug abusers and their nonaddicted siblings, some brain areas involved in addiction are larger (red) or smaller (blue), or function less efficiently (yellow), than in healthy, drug-free controls.

Science/AAAS

Primed for Addiction?

Families hand down many things from one generation to the next—and addiction can be one of them. A child of drug-addicted parents is eight times more likely to become an addict than a child growing up in a drug-free home. But genes aren't everything. Even in families whose very brains seem primed for addiction, some children still go on to lead productive lives free of drugs, according to new research.

Behavioral neuroscientist Karen Ersche of the University of Cambridge in the United Kingdom and colleagues had set out to examine whether drug abusers begin life with miswired brain circuitry or merely end up that way. Imaging studies of addicts show dramatic differences in brain areas involved in motivation, reward, and self-control, to name just a few. But it's less clear whether these differences are the cause or the effect of drug abuse. Because both addiction and brain structure are likely to be inherited traits, many researchers suspect that drug abusers have faulty brain circuitry based in their genes.

To explore the chicken-versus-egg question, Ersche and colleagues worked with 50 pairs of biological siblings; one in each pair was addicted to cocaine or amphetamines while the other had no history of drug abuse. Also included were 50 healthy, drug-free, unrelated volunteers. The researchers first tested the subjects' self-control. Participants pressed a left- or right-arrow key when seeing a similar arrow on a computer screen—unless they heard a tone, in which case they were to do nothing. People with poor self-control, including most drug addicts, find it difficult to refrain from pressing the key; studies show that impaired performance on the test is linked to irregularities in the brain areas involved in addiction.

Much to the researchers' surprise, the siblings who didn't use drugs performed as poorly on the test as the ones who did. All of the sibling pairs did worse than the healthy controls, the team reports in the 3 February issue of Science.

Brain scans also showed that both members of the sibling pairs had abnormal interconnections between parts of the brain that exert control and those involved with drive and reward. Some individual brain structures were abnormal as well; the putamen, which plays a key role in habit formation, was larger in the siblings than in control subjects, as was the medial temporal lobe, which is involved in learning and memory. Because these anomalies appeared in the siblings but not in the unrelated controls, Ersche believes the finding provides a measurable, biological basis for vulnerability to addiction.

Equally intriguing, she adds, is that even among siblings who share so many risk factors for addiction—genes, family environment, brain circuitry, and behavioral test results—"some people just don't go down that road. There must be other factors that convey resilience."

Of course, siblings differ in many ways, including their experiences in life. Imaging specialist Nora Volkow of the National Institute on Drug Abuse in Bethesda, Maryland, adds that key differences between the brains of the siblings might account for some of the resilience. For example, in the addicted sibling, an area called the orbitofrontal cortex, which provides for flexibility during changing circumstances, was smaller, possibly making it difficult to break out of compulsive patterns such as drug addiction. Increased activity in this region, on the other hand, is linked to positive emotions, which are thought to protect against addiction.

"The findings are good news," Volkow says. She explains that even in children as young as 4 to 12, traits such as self-control and flexibility can be improved by targeted interventions, including exercise training, martial arts, yoga, and computer games designed to enhance working memory (the ability to hold complex information in mind). These approaches, she says, could be used to help prevent addiction in those at risk for drug abuse.