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Even after years of research, it is still not clear which receptor sites or which monoamines are involved, although noradrenaline, serotonin and dopamine are all implicated. Neither does the theory explain how mania and depression can exist in the same patient. Much research has involved investigation of cerebrospinal fluid, blood and urine of patients to see if there are any abnormalities of monoamine metabolites. Although results may be complicated by diet, non-brain amines and the inevitable drug therapy, evidence indicates that bipolar depression is associated with a decrease in dopamine activity, mania with an increase in dopamine activity [or depletion of inhibitory gamma-amino butyric acid (GABA)] and unipolar depression with a decrease in noradrenaline or serotonin activity or both. Levodopa has been shown to produce symptoms of mania in patients with bipolar depression but not in those with unipolar depression. This still does not explain the swings in mood and little is known about how or why alternation between depression and mania occurs.

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