How the Immune System Influences Psychiatric Disorders

In a randomized controlled trial³ published in 2013, Miller and colleagues divided patients with treatment-resistant depression into two groups: one received a placebo, while the other received infusions of infliximab (Remicade), a medication that blocks the action of an inflammatory cytokine called tumor necrosis factor (TNF). At the end of the 12-week study period, results show a greater response to infliximab treatment compared to placebo, but only in patients whose baseline blood level of C reactive protein (CRP), a biomarker of inflammation, was above a certain level.

Among these patients, 62% demonstrated a reduction of at least 50% in their Hamilton Scale for Depression (HAM-D) scores, while only 33% of the placebo group had such a response. Additionally, the infliximab-treated responders had demonstrated significantly higher baseline concentrations of TNF, and compared with placebo-treated responders, they experienced greater reductions in CRP at the end of the study period.

These findings suggest that among patients with treatment-resistant depression, “there appears to be a subgroup of individuals whose depressive symptoms are driven by TNF-induced inflammation in a cause and effective manner,”⁴ and that TNF antagonism  “may improve depressive symptoms in patients with high baseline inflammatory biomarkers.”³ Some research has found higher rates of inflammation in people with atypical depression in particular.

Chronic psychological stress has been implicated in a problematic immune response that could lead to mental illness. Findings from a rodent study⁵ published this year in Biological Psychiatry indicate that “the brain’s interpretation of the stress is communicated out from the brain to the immune system and then from the immune system back to the brain,” said Godbout, who co-authored the research. “Part of this ‘circular’ response to the stress is the release of immune cells from the bone marrow.”

The researchers found that a particular type of immune cell called monocytes are preferentially released into circulation and then traffic to the brain and peripheral tissues, and they are also recruited by resident CNS cells.  “Functionally these monocytes provide inflammatory signals back to the brain that induce anxiety-like behavior,” Godbout noted. Blocking the release of monocytes or their trafficking to the brain prevented the development of stress-induced anxiety. He and his colleagues also found that monocytes influence sensitization to stress, in that the mice remained sensitized to stress weeks after the initial stress exposure. “Stress sensitization corresponded with a lower threshold to an acute stressor in which anxiety reoccurred following the release and subsequent trafficking of monocytes from the spleen to the brain.”