What Underlies Vulnerability to Drug Addiction?

Post by Flora Moujaes

What's the science? 

Why does regular drug use lead to addiction in some people but not others? Many factors can increase the risk of developing an addiction. For example, a family history of drug addiction has been shown to make people eight times as likely to develop a drug addiction. We know that drug addiction compromises the neural systems involved in goal-directed behaviour, shifting behavioural control of drug-related decisions towards the habit system. Drug addiction may also weaken cognitive control, which enables the flexible regulation of goal-directed and habitual actions, and intervenes when behaviour becomes maladaptive. Much less is known about resilience to developing a drug addiction. One hypothesis is that high-functioning drug users may be able to function at a normal level by recruiting compensatory brain systems, which may buffer the impact of their drug use. This week in PNAS, Ersche et al. use resting-state functional magnetic resonance imaging (rs-fMRI) to explore how addiction risk and resilience may be associated with changes in the functioning of key neural systems. 

How did they do it?

In order to examine the risk and resilience factors associated with drug addiction to either amphetamines or cocaine, the researchers collected data from 162 individuals who either 1) have a diagnosed drug addiction and a family history of drug addiction, 2) high-functioning drug use without diagnosis and no family history of drug addiction, 3) no drug use and family history of drug addiction, or 4) no drug use and no family history of drug addiction. They collected rsfMRI data which measures fluctuations in the brain’s blood-oxygen-level-dependent (BOLD) signal while an individual is at rest, and looked at six key striatal brain regions.

What did they find?

Familial risk and addiction: First, in order to examine how familial risk is associated with drug addiction, the authors compared individuals with a family history of drug addiction to individuals with no family history of drug addiction. They found that in individuals with high familial risk, whether drug users or siblings of drug users, there was reduced connectivity in two fronto-striatal pathways that are critical for goal-directed decision making: the orbitofrontal and ventromedial prefrontal cortical-striatal circuits. This indicates that individuals with a family history of drug addiction may be at greater risk of developing a drug addiction due to impaired goal-directed decision-making. 

Stimulant use and addiction: Secondly, in order to examine how stimulant use is associated with drug addiction, they compared individuals who regularly took stimulant drugs (both those who were officially diagnosed with drug addiction and high-functioning non-diagnosed drug users) to individuals who had not taken stimulant drugs (both the siblings of addicted individuals and healthy controls). They found that stimulant use was associated with reduced connectivity between areas associated with emotional awareness and habituation to pleasant or painful stimuli.

Resilience against addiction: Finally, they examined the interaction between familial risk and stimulant use. They found that the two groups who showed resilience to drug addiction (high-functioning non-diagnosed users and non-addicted siblings of drug users) showed increased connectivity in two regulatory control networks: 1) a network implicated in top-down inhibitory control, and 2) a network implicated in the regulation of habits. This indicates that defying the risk of developing a stimulant drug addiction may require increased efforts to control behaviour.

What's the impact?

Overall this study suggests that familial vulnerability for drug addiction and the administration of stimulant drugs are associated with reduced functional connectivity in networks implicated in goal-directed learning, including the pathway associated with negative feedback processing. This may increase the risk of maladaptive behaviours, such as drug use, becoming compulsive. On the other hand, resilient individuals appear to counteract the drive to addiction through increased connectivity in networks associated with goal-directed behaviour and the habitual control of behaviour. This study provides valuable insights into possible interactions between familial risk and stimulant drug use for the regulation of behavioural control. Such insights may inform novel strategies for therapeutic and preventative interventions for drug addiction.

Ersche et al. Brain networks underlying vulnerability and resilience to drug addiction. PNAS (2020). Access the original scientific publication here.