Importance of ‘inflammatory molecules’, but not necessarily of inflammation, in the pathophysiology of bipolar disorder and in the mechanisms of action of anti-bipolar drugs

Abstract

It is often supposed that inflammation plays a major role in the pathophysiology of bipolar disorder and that reduction of inflammation by the classical anti-bipolar drugs, the lithium ion (lithium), carbamazepine and valproic acid, partly explain their therapeutic effect. The present mini-review summarizes data for enhanced expression in bipolar patients of ‘inflammatory molecules’, i.e., cytokines and metabolites of arachidonic acid (e.g., prostaglandins) and the enzymes (e.g., COX2) that catalyze this metabolism. However, it points out that enhanced transmitter activity during manic phases may play a major part in this upregulation. It also shows that chronic treatment with any of the 3 anti-bipolar drugs, known to decrease expression of the enzyme that releases arachidonic acid (cPLA2) in whole brain, has this effect only in neurons, whereas it upregulates cPLA2 expression in astrocytes. Literature data are presented that this upregulation may have therapeutically beneficial effects in bipolar disorder, supporting increasing evidence for involvement of not only neurons but also astrocytes in bipolar disorder and anti-bipolar drug action.