Immune dysregulation in bipolar disorder

The concept that circulating molecules might influence mood and behavior is not new. Ancient Egyptians were the first to describe mental symptoms and they believed that mental diseases did not arise from affections in the brain. Hippocratic medicine explained mood, health, and illness based on the shifting balance of circulating “humors.” These crucial vitality-sustaining fluids were blood, choler (or yellow bile), phlegm, and melancholy (or black bile) (Porter, 2003). The excess of two fluids, blood and yellow bile, could lead to mania. Hippocrates believed that the excess of black bile (with no defined biological correlate) was responsible for depressive symptoms. In fact, melancholia literally means “black bile”: “when sadness and fear last for a long time, then it is melancholy” (Contreras, 2003). The idea that mood symptoms were not related to brain dysfunction was sustained for centuries. In the 19th century, the knowledge of brain biology improved significantly and the understanding of mental health and psychiatric disorders went through several revolutions. At this time, psychiatric disorders were regarded as “brain disorders,” though this concept was not able to provide a comprehensive approach to mood disorders. During the first half of the 20th century, there was a shift in the understanding of mood disorders, with an overemphasis on psychological explanations. Bipolar disorder is currently viewed as the result of a complex interplay among biological, psychological, and social factors. Several vulnerability factors, including genetic predisposition, traumatic life events, and personality traits have been found to increase the risk for developing bipolar disorder. Accordingly, bipolar disorder is conceptualized as a multisystem condition, impairing behavior, cognition, and autonomic, endocrine, and immune functions. In the present chapter, we review the evidence supporting a role for immune dysfunction in bipolar disorder. Immune system The immune system is composed of a network of specific cells and molecules that play a pivotal role in host defense and maintenance of homeostasis. The immune system has two main branches: innate and adaptive. Both branches act through humoral and cellular-mediated responses. The adaptive immune response consists of antibody- and cell-mediated responses which are carried out, respectively, by B and T lymphocytes. The main operating mechanism of the innate immune response is inflammation. Inflammation is traditionally regarded as a defense response of the body against infection or trauma.