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Immunology and Bipolar Disorder

Rashmi Nemade, Ph.D. & Mark Dombeck, Ph.D.

The immune system is the body's defense system. It protects the body from outside threats such as bacteria and viruses that cause infections. When the body comes under attack, immune cells such as T-lymphocytes, B-lymphocytes and immune proteins known as immunoglobulins attack the intruding bacteria or virus, hopefully defeating illness before it can become entrenched. Typically, an observed elevation in immune cells and proteins is an indication that the body is fighting an infection. Several studies have described abnormal fluctuations in the immune system which vary according to the state of bipolar illness. For example, T- and B-lymphocytes, IgG (immunoglobulin G), and IgM (immunoglobulin M) are increased in bipolar patients. This observation would lead to the conclusion that the bodies of individuals with bipolar disorder are fighting an infection. But it is unclear whether these findings are the cause or result of natural body responses to mood peaks and troughs or the use of medications. In addition to measuring immune system components in the study of bipolar disorders, infections have also been investigated for their contribution to bipolar symptoms.

body imageA simple infection by bacteria or viruses, a retroviral infection, or immune dysfunction can precipitate bipolar illnesses. Several varieties of brain infection have been known to cause either manic or depressed states. Bacterial infections such as syphilis and Lyme disease have neurological manifestations that can cause bipolar-like symptoms. At the same time, viral infections such as Epstein - Barr virus (EBV) and Herpes Simplex Virus (HSV) have been associated with bipolar disorder.

In the case of EBV, researchers have not been able to confirm that infection is a necessary step in developing bipolar depression. However, case studies documenting patients who had no history of bipolar disorder prior to EBV infection leads some researchers to continue considering EBV infection as a possible causal pathway.

While there is a definite connection between HSV infection and reduced cognitive functioning in bipolar individuals, there is no solid evidence suggesting that HSV infection caused bipolar disorder to occur. It is known that lithium, the primary medical treatment for bipolar disorders, inhibits the growth of HSV in laboratory situations, but exactly how this inhibitory role might function with regard to bipolar disorder is not known.

It is possible that neither EBV nor HSV themselves cause bipolar symptoms, but rather initiate a dysregulation of particular brain and body systems that ultimately lead to mood disorder onset. There are some researchers who believe that HIV (the virus that causes AIDS) may cause bipolar disorder, but it unknown whether manic-depressive behavior observed in AIDS cases is a result of the psychological impact of having a serious disease such as AIDS or if the disease itself causes the behavior.

A retrovirus is a special kind of virus, which causes infection by inserting its own DNA into the genes of its host. By altering the body's basic genetic machinery, a retrovirus can have a disproportionately large impact on the host's body. For example, HIV is a retrovirus which causes numerous symptoms across multiple body systems. If a retrovirus inserts itself into the genes in the ovary (egg) or testicles (sperm), it is conceivable that this virus can then be passed down from generation to generation. Thus, a person could have been infected by a bipolar-causing retrovirus in the late 1800's and passed it down to all of their children, grandchildren, etc. A specific retrovirus has not been identified in conjunction with bipolar disease, but more genetic studies may reveal that a retrovirus resides on one or many of the chromosomes thought to be involved in bipolar disorder. The pieces of the bipolar and infectious agent puzzle are not yet complete and further research is necessary to clarify this aspect of bipolar disease.

Another aspect of the immune system that is involved in bipolar disorders is that of autoimmunity. Autoimmune diseases result when the immune system becomes confused and can no longer distinguish between the body's own tissues and those which belong to an outside threat. As a consequence of this immune confusion, the body starts attacking itself. For example, in rheumatoid arthritis, the immune system attacks the joints, causing a disabling and painful inflammatory condition. The disease leads to destruction of the joints as well as systemic tissues throughout the body including the skin, blood vessels, heart, lungs, and muscles. Although currently there is no evidence linking bipolar disorders directly to an autoimmune condition, autoimmunity against the thyroid gland is well established. Graves' disease is the most common form of hyperthyroidism. It is caused when the body produces antibodies against the thyroid that have the effect of stimulating the thyroid into overproduction of thyroid hormone. In Ord's thyroiditis and Hashimoto's disease, a variety of antibodies against the thyroid gland cause hypothyroidism. Given that mood changes are associated with thyroid hormone imbalances, it is conceivable that thyroid autoimmunity is connected to bipolar disorders. However, as is the case with infectious diseases, there is no clear evidence that autoimmunity is necessarily involved in bipolar disorders. This new area of research will be interesting to monitor in the coming years.