How the Immune System Influences Psychiatric Disorders

Monocytes could also be elevated before stress even occurs, contributing to individual differences in vulnerability and resilience to its effects, according to another rodent study6 published in 2014 in the Proceedings of the National Academy of Sciences of the United States of America. “Animals with immune cells that release more pro-inflammatory cytokines in responses to endotoxin stimulation in vitro developed a more severe depression-like response to stress in vivo,” said Hodes.

Furthermore, these animals had more circulating monocytes before they were ever exposed to stress. The researchers were able to both induce and block the development of depression-like behavior by transplanting bone marrow from mice who, respectively, were more susceptible to stress and from those who lacked the gene for immune-mediated release of pro-inflammatory cytokines. Additionally, they were able to prevent stress susceptibility by prophylactically treating the mice with an antibody for a cytokine called interleukin-6 “that sequestered and neutralized IL-6 in the periphery and did not cross the blood brain barrier.”

Findings like those by Hodes and Godbout suggest that targeting inflammation could be an effective treatment strategy for certain patients with anxiety and depression, and results of ongoing research into how to accurately measure inflammation in the brain could facilitate the development of such treatments. “In addition, there is a great deal of interest in harnessing the immune system — particularly certain T cells — to improve brain health,” Miller said.

Meanwhile, simple blood tests can detect elevated levels of general inflammation, which are associated with non-response to antidepressant treatment and alterations in the brain’s reward circuitry, likely due to decreased dopamine, he explains. Patients with a high CRP level might respond better to drugs that are more likely to affect the brain’s dopamine pathways.

The bigger-picture message from these emerging findings is that the mind and body are inextricable. “As a whole we need to stop thinking of mental illness as a disease of the brain,” said Hodes. “The whole body is involved and as a result, the whole body can be treated.”    


  1. Louveau A, Smirnov I, Keyes TJ, et al. Structural and functional features of central nervous system lymphatic vessels. Nature; 2015; 523(7560):337-41.
  2. Haapakoski R, Mathieu J, Ebmeier KP, et al. Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder. Brain, Behavior, and Immunity; 2015; 49:206-15.
  3. Raison CL, Rutherford RE, Woolwine BJ, et al. A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry; 2013; 70(1):31-41.
  4. Felger JC, Miller AH. Neurotherapeutic Implications of Brain-Immune Interactions. Neuropsychopharmacology; 2014; 39(1):242-3.
  5. McKim DB, Patterson JM, Wohleb ES, et al. Sympathetic Release of Splenic Monocytes Promotes Recurring Anxiety Following Repeated Social Defeat. Biological Psychiatry; 2015; pii: S0006-3223(15)00598-3.
  6. Georgia E. Hodes, Madeline L. Pfau, Marylene Leboeuf, et al. Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress. Proceedings of the National Academy of Sciences of the United States of America; 2014; 111(45): 16136–16141.