Brain Volume Changes Seen in Opioid Users

Structural, functional alterations seen in opioid receptor-dense regions


Saloni Mehta, MBBS
Mehta

Researchers at the Yale School of Medicine found structural and functional alterations in specific brain regions of individuals with opioid use disorder. The study’s results were published in Radiology.

Opioids have a high potential for misuse, and opioid use is a major contributor to drug overdoses in the U.S.

According to the National Institute on Drug Abuse, in 2021, approximately 2.5 million adults in the U.S. had opioid use disorder. “We are in the midst of an opioid epidemic, with millions affected worldwide and more than 80,000 deaths related to opioid overdoses in the U.S. last year alone,” said Saloni Mehta, MBBS, postdoctoral associate in the Department of Radiology and Biomedical Imaging at the Yale School of Medicine. “We need to get a better understanding of the system-level neural alterations associated with opioid use disorder.”

In the study, Dr. Mehta and colleagues conducted a secondary analysis of data from the National Institutes of Health-funded Collaboration Linking Opioid Use Disorder and Sleep Study (CLOUDS), comparing participants with opioid use disorder on methadone treatment and healthy controls. The data included structural MRI and functional MRI (fMRI) exams performed between February 2021 and May 2023.

Researchers analyzed CLOUDS structural MRI data for 103 individuals with opioid use disorder and 105 individuals from the control group. They also analyzed the resting state fMRI data on 74 participants with opioid use disorder and 100 controls. The individuals with opioid use disorder were all recently stabilized with medication for the disorder (less than 24 weeks). The median age in the group with opioid use disorder was 37 years, and 40% were women. In the control group, the median age was 27 years, and 55% were women.

“Previous studies have been performed on small sample sizes, many of which included no women,” Dr. Mehta said. “Ours is a moderate sample size, approximately half of which is female.”

Whole-brain analysis revealed structural and functional alterations in opioid receptor-dense regions in the opioid use disorder group compared to healthy controls. In individuals with opioid use disorder, the thalamus and right medial temporal lobe of the brain were smaller in volume, while the cerebellum and brainstem were larger in volume than in controls. In the individuals with opioid use disorder, all these brain regions also had increased functional connectivity compared to controls.

“We observed widespread increases in global connectivity in individuals with opioid use disorder,” Dr. Mehta said. “Our goal is to understand better what could have caused these alterations to inform new treatment targets.”

Tensor-based morphometry (TBM) analysis of T1-weighted MRI scans shows a comparison of brain volumes in participants with opioid use disorder (OUD) and healthy control participants.

Tensor-based morphometry (TBM) analysis of T1-weighted MRI scans shows a comparison of brain volumes in participants with opioid use disorder (OUD) and healthy control participants. Widespread volume differences are observed between participants with OUD and healthy controls when accounting for total brain volume. Specifically, the bilateral thalamus, right caudate and orbitofrontal cortex, and right medial temporal lobe show lower volume in participants with OUD compared with healthy controls. The left medial temporal lobe, brainstem, bilateral cerebellum, left insula, and right dorsal posterior cingulate cortex show greater volume in those with OUD compared with healthy controls. All results are shown at P < .05 corrected for multiple comparisons. The color scale indicates the z statistic, whereby blue to pink represents smaller volumes in the OUD group compared with healthy controls, and red to yellow represents larger volumes in the OUD group compared with healthy controls. L = left, R = right.

https://doi.org/10.1148/radiol.240514 (c) RSNA 2024

Differences in Alteration Patterns Across the Sexes

The results also revealed that women in the group with opioid use disorder had smaller medial prefrontal cortex volume, compared to males in the same group.

“We found that alteration patterns in the medial prefrontal cortex—a core region involved in many mental health conditions—were different between men and women in the group with opioid use disorder,” Dr. Mehta said. “This highlights the importance of assessing sex differences in opioid use disorder neuroimaging studies.”

Dr. Mehta said the study builds a foundation for future research to investigate potential behavioral implications of these brain differences and whether they are permanent.

“Our eventual goal is to examine how brain alterations in individuals with opioid use disorder may be linked to outcome measures,” she said.

For More Information

Access the Radiology study, “Alterations in Volume and Intrinsic Resting-State Functional Connectivity Detected at Brain MRI in Individuals with Opioid Use Disorder,” and the related editorial, “Unveiling Functional and Structural Brain MRI Alterations in Opioid Use Disorder.”

Read previous RSNA News stories on imaging in recreational substance use/abuse: