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Immune Protein Role in Stress

A new focus on the links between the immune system and stress is needed to help pave the way for improved treatments of major depressive disorder (MDD), according to researchers at the University of Adelaide.

In a review of previous studies published in Frontiers in Neuroscience, the researchers concluded that a protein best known for its role in immunology, toll-like receptor 4 (TLR4), could be central to better understanding the disease.

“Current medications are insufficient to provide long-term relief from depression in most patients, and only one in seven patients shows any real benefit from the treatment,” says co-author Jia-Jun Liu.

Liu says the immune system has been increasingly associated with various psychosomatic illnesses. “With major depression, patients also have changes in their immunology. We know that a decrease in depressive symptoms is associated with a normalisation of this immunology. So these changes taking place in the immune system are playing an important role in patients’ disease.”

Liu’s review of the literature examining the brain as an immune organ demonstrates a clear role for TLR4 and its control of hormones in the body, all contributing to extended periods of stress and eventually depression.

“The immune-brain-hormone systems are in constant communication,” she says. “In the case of stress and MDD, all three systems may be dysfunctional in patients. The difficulty in finding targets for treatment lies in untangling these multi-layered relationships.

“The direct relationship between TLR4 and depression is still not fully understood, although timing and location of TLR4 activation appears to be important. More research is needed to better understand this connection.”