0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation |

Role of Translocator Protein Density, a Marker of Neuroinflammation, in the Brain During Major Depressive Episodes ONLINE FIRST

Elaine Setiawan, PhD1,2; Alan A. Wilson, PhD1,2,3; Romina Mizrahi, MD, PhD1,2,3,4; Pablo M. Rusjan, PhD1,2; Laura Miler, HBSc1,2; Grazyna Rajkowska, PhD5; Ivonne Suridjan, HBSc1,2,4; James L. Kennedy, MD1,2,3,4; P. Vivien Rekkas, PhD1,2; Sylvain Houle, MD, PhD1,2,3; Jeffrey H. Meyer, MD, PhD, FRCPC1,2,3,4
[+] Author Affiliations
1Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
2Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
3Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
4Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
5Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson
JAMA Psychiatry. Published online January 28, 2015. doi:10.1001/jamapsychiatry.2014.2427
Text Size: A A A
Published online

Importance  The neuroinflammatory hypothesis of major depressive disorder is supported by several main findings. First, in humans and animals, activation of the immune system causes sickness behaviors that present during a major depressive episode (MDE), such as low mood, anhedonia, anorexia, and weight loss. Second, peripheral markers of inflammation are frequently reported in major depressive disorder. Third, neuroinflammatory illnesses are associated with high rates of MDEs. However, a fundamental limitation of the neuroinflammatory hypothesis is a paucity of evidence of brain inflammation during MDE. Translocator protein density measured by distribution volume (TSPO VT) is increased in activated microglia, an important aspect of neuroinflammation.

Objective  To determine whether TSPO VT is elevated in the prefrontal cortex, anterior cingulate cortex (ACC), and insula in patients with MDE secondary to major depressive disorder.

Design, Setting, and Participants  Case-control study in a tertiary care psychiatric hospital from May 1, 2010, through February 1, 2014. Twenty patients with MDE secondary to major depressive disorder and 20 healthy control participants underwent positron emission tomography with fluorine F 18–labeled N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide ([18F]FEPPA). Patients with MDE were medication free for at least 6 weeks. All participants were otherwise healthy and nonsmokers.

Main Outcomes and Measures  Values of TSPO VT in the prefrontal cortex, ACC, and insula.

Results  In MDE, TSPO VT was significantly elevated in all brain regions examined (multivariate analysis of variance, F15,23 = 4.5 [P = .001]). The magnitude of TSPO VT elevation was 26% in the prefrontal cortex (mean [SD] TSPO VT, 12.5 [3.6] in patients with MDE and 10.0 [2.4] in controls), 32% in the ACC (mean [SD] TSPO VT, 12.3 [3.5] in patients with MDE and 9.3 [2.2] in controls), and 33% in the insula (mean [SD] TSPO VT, 12.9 [3.7] in patients with MDE and 9.7 [2.3] in controls). In MDE, greater TSPO VT in the ACC correlated with greater depression severity (r = 0.63 [P = .005]).

Conclusions and Relevance  This finding provides the most compelling evidence to date of brain inflammation, and more specifically microglial activation, in MDE. This finding is important for improving treatment because it implies that therapeutics that reduce microglial activation should be promising for MDE. The correlation between higher ACC TSPO VT and the severity of MDE is consistent with the concept that neuroinflammation in specific regions may contribute to sickness behaviors that overlap with the symptoms of MDE.

Sign in to download this free article PDF

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal

Some tools below are only available to our subscribers or users with an online account.

Sign in to download this free article PDF

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
Jobs

Fellowship in Laryngology
Robert T. Sataloff and Associates
Philadelphia, PA

BC/BE Family Practitioner with OB
Confluence Health
Omak, WA

brightcove.createExperiences();