In a paper published in Frontiers in Neuroscience, a team based in the University of Adelaide’s School of Medical Sciences argues that current treatments for major depressive disorder (MDD) lack effectiveness, pointing to other underlying causes of depression that usually go untreated.
The researchers reviewed previous studies and concluded that the protein best known for its role in immunology, called “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,” said co-author and PhD student in Physiology at the University of Adelaide, JiaJun (“JJ”) Liu. “Only one in seven patients shows any real benefit from the treatment.
“Given the huge burden placed on individuals, families and society from depression, new insights into the condition – and new medications – are desperately needed.”
Liu said scientists have known for years that stress can lead to ill health, and the immune system has been increasingly associated with various psychosomatic illnesses.
“But stress has proven difficult to study because it's hard to pinpoint exactly what it does in the body,” she said.
“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. 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,” she said.
“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.”Jump to next article