Study links brain inflammation to suicidal thinking in depression



Philadelphia, PA, September 21, 2017

Patients with major depressive disorder (MDD) have increased brain levels of a marker of microglial activation, a sign of inflammation, according to a new study in Biological Psychiatry by researchers at the University of Manchester, United Kingdom. In the study, Dr. Peter Talbot and colleagues found that the increase in the inflammatory marker was present specifically in patients with MDD who were experiencing suicidal thoughts, pinning the role of inflammation to suicidality rather than a diagnosis of MDD itself.

“Our findings are the first results in living depressed patients to suggest that this microglial activation is most prominent in those with suicidal thinking,” said Dr. Talbot. Previous studies suggesting this link have relied on brain tissue collected from patients after death.

“This paper is an important addition to the view that inflammation is a feature of the neurobiology of a subgroup of depressed patients, in this case the group with suicidal ideation,” said Dr. John Krystal, Editor of Biological Psychiatry. “This observation is particularly important in light of recent evidence supporting a personalized medicine approach to depression, i.e., that anti-inflammatory drugs may have antidepressant effects that are limited to patients with demonstrable inflammation.”

In the study, first author Dr. Sophie Holmes and colleagues assessed inflammation in 14 patients with moderate-to-severe depression who were not currently taking any antidepressant medications. Immune cells called microglia activate as part of the body’s inflammatory response, so the researchers used a brain imaging technique to measure a substance that increases in activated microglia.

The evidence for immune activation was most prominent in the anterior cingulate cortex, a brain region involved in mood regulation and implicated in the biological origin of depression, confirming the results of a previous study that first identified altered microglial activation in medication-free MDD patients. Smaller increases were also found in the insula and prefrontal cortex.

“The field now has two independent reports — our study and a 2015 report by Setiawan and colleagues in Toronto — showing essentially the same thing: that there is evidence for inflammation, more specifically microglial activation, in the brains of living patients during a major depressive episode,” said Dr. Talbot.

This link suggests that among depressed patients, neuroinflammation may be a factor contributing to the risk for suicidal thoughts or behavior. According to Dr. Talbot, the findings “emphasise the importance of further research into the question of whether novel treatments that reduce microglial activation may be effective in major depression and suicidality.”

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Notes for editors

The article is "Elevated translocator protein in anterior cingulate in major depression and a role for inflammation in suicidal thinking: a PET study," by Sophie E. Holmes, Rainer Hinz, Silke Conen, Catherine J. Gregory, Julian C. Matthews, Jose M. Anton-Rodriguez, Alexander Gerhard, and Peter S. Talbot (https://doi.org/10.1016/j.biopsych.2017.08.005). It appears in Biological Psychiatry, published by Elsevier.

Copies of this paper are available to credentialed journalists upon request; please contact Rhiannon Bugno at Biol.Psych@UTSouthwestern.edu or +1 214 648 0880. Journalists wishing to interview the authors may contact Peter S. Talbot, MD, MRCPsych, at peter.talbot@manchester.ac.uk.

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

John H. Krystal, M.D., 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 6th out of 142 Psychiatry titles and 10th out of 258 Neurosciences titles in the Journal Citations Reports® published by Thomson Reuters. The 2016 Impact Factor score for Biological Psychiatry is 11.412.