Influenza Challenge in Mood Disorders

Summary

The aim of this project is to evaluate the efficacy of the influenza vaccine in individuals with major depressive disorder (MDD) as well as to elucidate the nature of the immunological abnormalities in MDD using a quasi-experimental design. Specifically, the investigators plan to induce transient, mild inflammation in medically-healthy study participants using the influenza vaccine. Initially the investigators will conduct a pilot project with up to 20 individuals in order to evaluate the time-point at which the peak inflammatory response to the vaccine occurs. Subjects will receive the seasonal influenza vaccine and provide blood samples 4 hours, 2 days, and 30 days post vaccination. Subsequent to the pilot study, both depressed and psychiatrically-healthy participants will be randomized in a parallel group, double-blind design so that they receive either influenza vaccine (seasonal vaccine) or saline (i.m). At baseline, subjects will provide a blood sample, complete a number of rating scales to measure mood and fatigue, and may complete approximately one hour of MRI scanning with or without simultaneous EEG recording. Two-days post vaccination, they will provide a second blood sample, complete more clinical ratings and may complete another identical MRI session with or without simultaneous EEG. Four weeks later, participants will be asked to return to provide a third blood sample and complete additional clinical ratings. The blood samples will be used to measure both innate and adaptive immune function and may be used to correlate the vaccine-induced immunological changes to neurophysiological changes in the brain measured by MRI and/or EEG.

Timeline

Start

2015-07

Primary completion

2016-03

Completion

2016-03

Publications

• Background Irwin MR, Miller AH. Depressive disorders and immunity: 20 years of progress and discovery. Brain Behav Immun. 2007 May;21(4):374-83. doi: 10.1016/j.bbi.2007.01.010. Epub 2007 Mar 13.
• Background Blume J, Douglas SD, Evans DL. Immune suppression and immune activation in depression. Brain Behav Immun. 2011 Feb;25(2):221-9. doi: 10.1016/j.bbi.2010.10.008. Epub 2010 Oct 16.
• Background Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 2008 Jan;9(1):46-56. doi: 10.1038/nrn2297.
• Background Price JL, Drevets WC. Neurocircuitry of mood disorders. Neuropsychopharmacology. 2010 Jan;35(1):192-216. doi: 10.1038/npp.2009.104.
• Background Robinson OJ, Cools R, Carlisi CO, Sahakian BJ, Drevets WC. Ventral striatum response during reward and punishment reversal learning in unmedicated major depressive disorder. Am J Psychiatry. 2012 Feb;169(2):152-9. doi: 10.1176/appi.ajp.2011.11010137.
• Background Savitz J, Drevets WC. Bipolar and major depressive disorder: neuroimaging the developmental-degenerative divide. Neurosci Biobehav Rev. 2009 May;33(5):699-771. doi: 10.1016/j.neubiorev.2009.01.004. Epub 2009 Jan 21.
• Background Eisenberger NI, Berkman ET, Inagaki TK, Rameson LT, Mashal NM, Irwin MR. Inflammation-induced anhedonia: endotoxin reduces ventral striatum responses to reward. Biol Psychiatry. 2010 Oct 15;68(8):748-54. doi: 10.1016/j.biopsych.2010.06.010. Epub 2010 Aug 16.
• Background Harrison NA, Brydon L, Walker C, Gray MA, Steptoe A, Critchley HD. Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity. Biol Psychiatry. 2009 Sep 1;66(5):407-14. doi: 10.1016/j.biopsych.2009.03.015. Epub 2009 May 7.

Drugs

Indications