How the Immune System Influences Psychiatric Disorders

In recent years there has been an increasing awareness of the close connection between physiological states and mental health. New findings suggest the mind-body relationship is even more direct than previously imagined and suggest a potential new target for treatment: the immune system. Until recently, it was believed that the brain is “immune-privileged,” operating separately from the peripheral immune system (that of the rest of the body) with minimal interaction between the two.

In a ground-breaking paper1 published in Nature this year, University of Virginia researchers reported the discovery of a lymphatic drainage system in the central nervous system (CNS), which it was previously believed to lack.

“There is growing evidence, such as the Nature paper, that there is more normal trafficking between the immune system in the brain and that in the body than previously recognized,” Georgia Hodes,PhD, a research track assistant professor in the department of neuroscience at the Icahn School of Medicine at Mount Sinai in New York, told Psychiatry Advisor. She and her colleagues believe that chronic alterations of the peripheral immune system — even those that are non-pathological but still at the high end of the normal range — do indeed cross into the brain, where they can alter synaptic plasticity and result in mood disorders.

“There is dynamic communication between the brain and the immune system,” Jonathan P. Godbout, PhD, an associate professor in the department of neuroscience at Ohio State University, told Psychiatry Advisor. “These two systems talk to each other using many specialized pathways,” he says. One such pathway involves the release of inflammatory cytokines released during the immune system’s response to illness, infection or other stressors. A multitude of studies2 have found higher levels of inflammation among patients with major depressive disorder, and recent findings from human and rodent studies offer a more nuanced understanding of this connection.

“Cytokines released as part of the inflammatory response can get into the brain and alter the function of neurotransmitters like serotonin, dopamine and glutamate, all of which play a role in depression,” said Andrew H. Miller, MD, a professor of psychiatry and behavioral sciences and research director of psychiatric oncology at Emory University School of Medicine. Because of these effects, cytokines can disrupt brain circuits that govern motivation, motor activity, anxiety, arousal and alarm, leading to “many of the symptoms that characterize depression and anxiety disorders,” he told Psychiatry Advisor.