News Release

Brain gene expression patterns altered by chronic opioid use

Findings implicate proinflammatory signaling and synaptic remodeling

Peer-Reviewed Publication


Philadelphia, August 10, 2021 – The epidemic of opioid abuse affects millions of people worldwide, but researchers know surprisingly little about the molecular changes caused by opioids in the human brain. A new study, which appears in Biological Psychiatry, published by Elsevier aims to better understand those molecular events; showing that genes are expressed differently in the brains of people with opioid use disorder (OUD) compared to those not using opioids.

“These changes may explain not only the addictive properties of opioids but what ultimately causes harm to the brain and the person suffering with opioid use disorder,” said Ryan Logan, PhD, an Associate Professor at Boston University’s School of Medicine, Boston, MA, USA and senior author of the study.

“These gaps in our understanding of opioids’ actions in the brain limits our ability to develop more effective therapies,” Dr. Logan explained. “To address this, we employed new methods to identify novel molecular players directly in the brains of people who struggled with opioid use disorder.”

Dr. Logan and his team obtained autopsy brain tissue from 20 subjects with OUD and chronic opioid use, and 20 without a history of opioid use. To identify differing patterns of gene expression, they used RNA sequencing (RNAseq), a technique that reflects how strongly genes are being expressed in a given tissue. RNAseq of the dorsolateral prefrontal cortex and the nucleus accumbens, two brain areas strongly associated with addiction pathophysiology, showed that certain genes were expressed differently in people with OUD compared to controls. The affected genes fell into two broad categories: genes encoding proinflammatory immune molecules; and those involved in remodeling of the extracellular matrix, which suggests that connections between neurons may have been altered by opioid use. The results also indicated that the brain’s resident immune cells, called microglia, were present at higher levels in the brains of people with OUD.

“We discovered several important molecular pathways that are integral in mediating the consequences of chronic opioid use on the brain. These molecules are responsible for shaping and maintaining the local environment required for neurons to function properly, as well as molecules critical for local inflammation that may impact the brain’s response to opioids. Together, these players represent new targets in both the pathology and treatment of opioid use disorder,” said Dr. Logan. 

John Krystal, MD, Editor of Biological Psychiatry, said of the study: “The deeper we understand opioid use disorders, the more complex is the biology that emerges. This study highlights that opioid dependency is associated with expected changes in markers of neural response and plasticity, but also with neuro-inflammatory changes associated with microglia. These findings suggest important new directions that can be followed in larger studies and that broaden our view of the neurobiology, and potentially treatment, of opioid use disorder.”


Notes for editors
The article is "Transcriptional alterations in dorsolateral prefrontal cortex and nucleus accumbens implicate neuroinflammation and synaptic remodeling in opioid use disorder," by Marianne Seney, Sam-Moon Kim, Jill Glausier, Mariah Hildebrand, Xiangning Xue, Wei Zong, Jiebiao Wang, Micah Shelton, BaDoi Phan, Chaitanya Srinivasan, Andreas Pfenning, George Tseng, David Lewis, Zachary Freyberg, Ryan Logan ( It appears as an Article in Press in Biological Psychiatry, published by Elsevier.

Copies of this paper are available to credentialed journalists upon request; please contact Rhiannon Bugno at  or +1 254 522 9700. Journalists wishing to interview the authors may contact Ryan Logan at or +1 617 358 9565.

The authors’ affiliations and disclosures of financial and conflicts of interests are available in the article.

John H. Krystal, MD, is Chairman of the Department of Psychiatry at the Yale University School of Medicine, Chief of Psychiatry at Yale-New Haven Hospital, and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available here.

About Biological Psychiatry
Biological Psychiatry is the official journal of the Society of Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal publishes both basic and clinical contributions from all disciplines and research areas relevant to the pathophysiology and treatment of major psychiatric disorders.

The journal publishes novel results of original research which represent an important new lead or significant impact on the field, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Reviews and commentaries that focus on topics of current research and interest are also encouraged.

Biological Psychiatry is one of the most selective and highly cited journals in the field of psychiatric neuroscience. It is ranked 7th out of 156 Psychiatry titles and 11th out of 273 Neurosciences titles in the Journal Citations Reports® published by Clarivate Analytics. The 2020 Impact Factor score for Biological Psychiatry is 13.382.

About Elsevier
As a global leader in information and analytics, Elsevier helps researchers and healthcare professionals advance science and improve health outcomes for the benefit of society. We do this by facilitating insights and critical decision-making for customers across the global research and health ecosystems.

In everything we publish, we uphold the highest standards of quality and integrity. We bring that same rigor to our information analytics solutions for researchers, health professionals, institutions and funders.

Elsevier employs 8,100 people worldwide. We have supported the work of our research and health partners for more than 140 years. Growing from our roots in publishing, we offer knowledge and valuable analytics that help our users make breakthroughs and drive societal progress. Digital solutions such as ScienceDirect, Scopus, SciVal, ClinicalKey and Sherpath support strategic research management, R&D performance, clinical decision support, and health education. Researchers and healthcare professionals rely on our 2,500+ digitized journals, including The Lancet and Cell; our 40,000 eBook titles; and our iconic reference works, such as Gray's Anatomy. With the Elsevier Foundation and our external Inclusion & Diversity Advisory Board, we work in partnership with diverse stakeholders to advance inclusion and diversity in science, research and healthcare in developing countries and around the world.

Elsevier is part of RELX, a global provider of information-based analytics and decision tools for professional and business customers.

Media contact
Rhiannon Bugno, Editorial Office
Biological Psychiatry
+1 254 522 9700

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.