Opioid use disorder is associated with changes in brain structure, function

Brain volume and function are altered in individuals with opioid use disorder, a new Yale study finds.

Using magnetic resonance imaging (MRI) and functional MRI (fMRI), researchers observed the alterations in several brain regions, some of which differed between men and women.

The findings, published Dec. 10 in the journal Radiology, are a step toward understanding how such alterations occur, whether they are linked to treatment outcomes, and how they might change over time, researchers said.

The opioid epidemic continues to take a toll in the United States, with more than 80,000 deaths from opioid overdose occurring annually in recent years.

"While we know the pharmacology of opioids to some extent, we know less about the neurobiology and system-level alterations that occur in the brain with opioid use," said lead author Saloni Mehta, a postdoctoral associate in the lab of Dustin Scheinost, an associate professor of radiology and biomedical imaging at Yale School of Medicine.

To better understand these effects on the brain, Mehta and her colleagues used MRI to measure brain volume in 208 individuals and fMRI to measure brain function in 174 individuals. Participants either had no known neurological or mental health illnesses or met the criteria for opioid use disorder and had recently been stabilized on the opioid use treatment methadone.

The researchers found widespread structural and functional alterations in the participants with opioid use disorder. Several brain regions - including the thalamus, brainstem, cerebellum, and the medial temporal lobe, which includes the hippocampus and amygdala - had both structural and functional alterations. Each of these regions have high densities of opioid receptors and have been shown in past research to have unique roles in addiction, said the researchers.

The study also explored sex differences.

"Previous studies have shown there are some sex differences in substance use," said Mehta. "For example, women have a faster progression from initial use to misuse than men."

In the current study, researchers found that the medial prefrontal cortex - a region involved in many higher order cognitive functions, such as decision-making - was larger in healthy males than in healthy females. But among participants with opioid use disorder, females had larger volumes than males. The finding warrants further research, said Mehta, and highlights the need to include women in these types of studies.

The researchers are following these participants for up to six months and will assess opioid use relapse and treatment retention, as well as the neural correlates of pain, sleep, relapse, and treatment retention in opioid use disorder. The participants and the current study are part of the Collaboration Linking Opioid Use Disorder and Sleep study, which is supported by National Institutes of Health's Helping to End Addiction Long-term Initiative.

"We're also interested in understanding the causal mechanisms of these brain alterations," said Mehta. "Future research could investigate whether the opioid receptors in these regions or their downstream effects play a role."

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