Abstract
Regular drug use can lead to addiction, but not everyone who takes drugs makes this transition. How exactly drugs of abuse interact with individual vulnerability is not fully understood, nor is it clear how individuals defy the risks associated with drugs or addiction vulnerability. We used resting-state functional MRI (fMRI) in 162 participants to characterize risk- and resilience-related changes in corticostriatal functional circuits in individuals exposed to stimulant drugs both with and without clinically diagnosed drug addiction, siblings of addicted individuals, and control volunteers. The likelihood of developing addiction, whether due to familial vulnerability or drug use, was associated with significant hypoconnectivity in orbitofrontal and ventromedial prefrontal cortical-striatal circuits-pathways critically implicated in goal-directed decision-making. By contrast, resilience against a diagnosis of substance use disorder was associated with hyperconnectivity in two networks involving 1) the lateral prefrontal cortex and medial caudate nucleus and 2) the supplementary motor area, superior medial frontal cortex, and putamen-brain circuits respectively implicated in top-down inhibitory control and the regulation of habits. These findings point toward a predisposing vulnerability in the causation of addiction, related to impaired goal-directed actions, as well as countervailing resilience systems implicated in behavioral regulation, and may inform novel strategies for therapeutic and preventative interventions.
Highlights
The use of addictive drugs is a growing global public health problem
Familial risk of addiction was associated with significantly reduced functional connectivity in frontostriatal pathways between the ventromedial caudate (vmCAU) seed with the rostral anterior cingulate cortex, medial, though mainly lateral, OFC, and medial prefrontal cortex
Using seed-based correlational analysis in corticostriatal systems in four groups, we identified distinct, lateralized abnormalities in functional connectivity strength associated with both increased risk of, and resilience to, developing stimulant addiction
Summary
The use of addictive drugs is a growing global public health problem. Drug addiction develops with persistent drug use, and individuals who are vulnerable to developing addiction may do so as quickly as within their first year of use [1]. The term “resilience” refers to protective factors that help individuals to successfully cope with or overcome exposure to significant risk, adversity, or potentially harmful environments [7] These factors may include personality traits and attitudes, supportive environments [8], and neural systems that are more robust to, or able to compensate for, adverse exposures [9]. Understanding how potentially vulnerable adults defy the risk of addiction may inform the development of more effective treatment strategies for individuals affected by the disorder. Resting-state functional connectivity provides novel insight into variations in neural networks associated with addiction to stimulant drugs in individuals with and without a family history of addiction, and both with and without personal drug use. It is conceivable that defying the risk of developing stimulant drug addiction requires increased efforts to control behavior—a hypothesis that may open up new pathways for therapeutic and preventative strategies
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