Talk like a behavioural neuroscientist

Alcohol or other substance use disorders — medical conditions in which someone struggles to control their alcohol or drug use, despite negative consequences

Bacterial endotoxin — the outer membrane of a bacterial cell that causes an immune response

Cognitive performance — how well the brain carries out mental tasks such as memory, attention and decision-making

Cortisol — a hormone released in response to stress

Cytokines — proteins released by immune cells that coordinate the body’s immune response

Early life adversity — negative experiences during childhood

Magnetic resonance imaging (MRI) — a technique that can take images of a living brain

Stress response — how the body reacts to challenges or threats

White matter — bundles of nerve fibres that allow different brain regions to communicate

“Addictive disorders have tremendous costs for afflicted individuals, their families and their communities,” says Professor Ashley Acheson, a behavioural neuroscientist at the University of Arkansas for Medical Sciences. “If we better understood what makes people vulnerable to addiction, we could do better at preventing it.” Ashley’s research focuses on identifying behavioural and biological traits associated with addiction risk factors, such as having a family history of alcohol or other substance use disorders and exposure to early life adversity. “Just having these risk factors doesn’t mean someone will develop alcohol or drug problems,” he emphasises. “However, they are more likely to have behavioural characteristics that put them at increased risk.”

Research by Ashley and others has found these characteristics include things like increased impulsivity and, to a lesser extent, increased tendencies for depression and anxiety. The underlying biology driving these behavioural characteristics is much less clear, and Ashley believes that understanding this may be critical for improving prevention and treatment of addictive disorders. Much of this work has been done as part of the Family Health Patterns Project, a long-running study aimed at identifying behavioural and biological factors underlying risk for addictions, started by Professor William Lovallo in 2001.

What biological systems does Ashley study?

Ashley and his team have focused on studying brain differences associated with having a family history of alcohol or other substance use disorders. They have found evidence for reduced or altered white matter in frontal regions of the brain which are critical for decision-making and impulse control. They have also found evidence for altered brain activity while performing tasks involving these same processes.

Ashley and his team have found that a family history of alcohol or other substance use disorders is also associated with decreased stress responses. They observed this by asking young adults to take part in a mock job interview or give a short speech – situations in which most people feel nervous. Typically, stress causes the heart to beat faster and leads to a spike in the hormone cortisol. However, those with a family history of alcohol or other substance use disorders generally had smaller increases in heart rate and cortisol.

While decreased stress responses may seem beneficial, this could be problematic as stress hormones play important roles in regulating the immune system. This led Ashley to hypothesise that immune regulation could be altered or impaired in people with a family history of alcohol or other substance use disorders. Indeed, blood tests showed that having a family history of alcohol or other substance use disorders was associated with having more white blood cells, and when Ashley and the team exposed these immune cells to bacterial endotoxin in the lab, more cytokines were released. They are now studying why this immune overreaction occurs, and how it may affect the brain. “We think that altered immune regulation and increased immunoreactivity could result in neural changes that are responsible for risk-related behavioural characteristics,” says Ashley.

How does Ashley study brains and behaviours?

Ashley uses advanced magnetic resonance imaging (MRI) techniques to capture high resolution anatomical images of young adults’ brains. For example, diffusion MRI tracks water movement and can be used to study white matter characteristics, while functional MRI can be used to study blood flow through the brain. “Brain differences in people with alcohol or drug problems are often assumed to be a consequence of excessive use,” explains Ashley. “But we have seen similar differences in at-risk people before alcohol or drug problems start.”

To assess behavioural traits, Ashley and the team use self-reported measures. Participants complete questionnaires about their mood, social behaviours and alcohol and drug use, and they take computer-based tests of attention, memory and reactions to stimuli. Decision-making tasks are also important. For example, participants are asked whether they would rather receive a smaller reward now or wait for a larger one later. By varying the size and timing of rewards, Ashley and the team can observe how participants value immediate versus delayed outcomes, giving insight into self-control and future planning. They have discovered that participants with a family history of alcohol or other substance use disorders are more likely to choose smaller, immediate rewards than larger delayed ones. They have also observed that people who were exposed to more early life adversity (whether or not this was associated with a family history of alcohol or other substance use disorders) are less likely to value delayed rewards.

Why are some people at increased risk of addiction?

“We don’t know for sure why some people have an increased risk of addiction,” says Ashley. “However, we have found that having a family history of alcohol or other substance use disorders and exposure to early life adversity can set a chain of events in motion that can increase the risk for addiction.” The team believes that altered immune system regulation contributes to neurological changes, including disruption to white matter development and white matter damage. These brain changes are linked to cognitive differences, such as not valuing delayed rewards. This reduced cognitive control can influence behaviour, contributing to traits such as impulsivity and, ultimately, making people more vulnerable to addictions.

The HEALthy Brain and Child Development Study

“At the moment, we don’t know how much of addiction risk is inherited or a result of stress and other exposures during pregnancy and early life,” says Ashley. To help better understand this, Ashley is one of the principal investigators of the nationwide HEALthy Brain and Child Development (HBCD) Study. “This is the largest study of childhood brain development ever conducted in the US,” he says. “We are following over 7000 mother-child pairs from before birth to at least age 10, to investigate how external factors influence brain development throughout childhood.” The study uses MRI, other brain scanning techniques, cognitive tests and observations of family interactions to track how children’s brains develop over time. Researchers also examine how external factors, including parental alcohol and drug use, early life adversity, and the social and physical environments children grow up in, affect development.

Could we prevent addiction?