Bipolar disorder: Neurochemistry and drug mechanisms.

Extract: The alternating states of mania, depression and mood moderation (euthymia) are so distinct that biological research in psychiatry was attracted to the study of bipolar disorders very early on. Moreover, the discovery of lithium as a simple metal ion that had a strong mood-stabilizing effect suggested that a simple biological pathophysiology might be easily discovered in manic-depressive illness and that this might lead the way to major biological discoveries in other mental disorders and human behavior in general. Overall this story has been heroic and exciting but it has left us in 2005 still without any biological diagnostic test or clear pathophysiological abnormality in manic-depressive illness. Early studies looked for urinary or spinal fluid abnormalities of metabolites of the major monoamine neurotransmitters (chemicals that contain an amino group attached to a carbon backbone in the nervous system, which carry signals between neurons), noradrenaline, serotonin and dopamine. Often, early findings were not replicated, or if replicated they turned out to be secondary to the hyperactivity that occurs in mania or the hypoactivity and weight loss observed in depression.