Our thanks to Professor Yehuda Shoenfeld, M.D., member of AARDA's Scientific Advisory Board (see "Source" at end of article)
An interesting connection has been found between smell impairment and depression in patients with systemic lupus erythematous (SLE), a complex multi-organ autoimmune disease affecting mainly women and currently having no definitive cure. In SLE, as with other autoimmune diseases, the immune system attacks the body's own cells and tissues, resulting in inflammation and tissue damage. The exact mechanisms for the development of SLE are still unclear, but its pathogenesis (origin and development) is probably a multi-factorial process in which autoantibodies (antibodies against self) have an important role.
About 10 percent of SLE patients suffer from central nervous system (CNS) symptoms, including mood disturbances, psychotic attacks, and others. Patients with CNS lupus have up to 20 specific autoantibodies detected in their bloodstream. Among them, one is targeted to the cell's ribosome, called the anti-phosphoribosomal (anti-PR) antibody. The ribosome, an extremely small portion of the submicroscopic structure of a cell, functions to receive genetic information and translates those instructions into protein.
According to studies conducted in the Sheba Medical Center, Israel, the anti-PR autoantibodies might be implicated in the pathogenesis of CNS lupus. Mice were intracerebroventricular (within a small cavity in the brain) injected with anti-PR antibodies, and their behavior was analyzed after they were placed in a bucket of water. In such a situation, normal mice will swim endlessly in the bucket while depressed mice will give up and just float. The anti-PR-injected mice exhibited a depression-like behavior when compared to those injected with a pool of non-specific antibodies.
This antibody-induced depression could be treated effectively with neutralizing antibodies, antidepressant medications like Prozac, or prolonged exposure to orange fragrance. Staining these antibodies has shown them to bind specifically to the limbic areas of the mice brains and amygdala, a part of the olfactory (sense of smell) system. Moreover, the mice's ability to respond to menthol odor was significantly decreased, indicating impaired olfactory function for the anti-PR-injected mice.
Given the observations on mice, one might question whether patients with lupus also had an abnormality in their sense of smell. SLE patients were screened, and they also exhibited a reduced smelling capacity, especially those with CNS involvement. Not surprisingly, according to previous studies, their brains showed a reduced size of the amygdala.
So how might this information be used by patients and their caregivers? Physicians and scientists today are becoming aware that smell impairment may be an early indicator of some CNS diseases. Every year, thousands of people develop problems with their sense of smell. A temporary loss of smell can be caused by a stuffy nose, smoking, or infection; but a permanent loss of smell may be caused by a process in which there is damage to brain areas that process smell (the olfactory cortex) or to nerve cell projections into the nose.
Due to its vast connections to other parts of the brain, the sense of smell can provide a natural window to the brain. Freud, the father of psychoanalysis, believed that a biopsy taken from inside the nose may be able to provide clues or treat some neurological and psychiatric disorders. Indeed, many patients complain of losing their sense of smell months before developing Parkinson's, schizophrenia, or Alzheimer's disease. This might be due to the fact that limbic areas of the brain, which are important in the origin and development of these diseases, are strongly involved in the smelling process.
More research should be done for unraveling the connections between smell, CNS disease, and various autoimmune disorders.
--Source: Adapted from "Depression, smell...and autoimmune diseases," S. Kivity, Dept. of Medicine 'A and C', Sheba Medical Center, Tel Hashomer, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Netta Shoenfeld, Dept. of Medicine 'B', Sheba Medical Center, Center for Autoimmune Diseases, Tel Hashomer, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; and Yehuda Shoenfeld, Head, Dept. of Medicine 'B' and Center for Autoimmune Disease, Sheba Medical Center, and Incumbent of the Laura Schwarz-Kipp Chair for Research of Autoimmune Diseases, Sackler Faculty of Medicine, Tel-Aviv University, Tel Hashomer, Israel (Note to medical professionals: For "Further reading," contact AARDA.)
