5-HT and depression: is the glass half-full?

Mood disorders such as major depression are common illnesses with considerable morbidity and significant mortality. A long-standing theory is that a breakdown in brain serotonin (5-hydroxytryptamine; 5-HT) signalling is critically involved in the symptoms and drug treatment of clinical depression. However, the nature of this 5-HT defect has proved to be frustratingly elusive, and it remains unclear how the 5-HT signalling effects of antidepressant drugs might alter neuropsychological mechanisms to bring about relief of depressed mood. This article highlights recent discoveries that advance our understanding of how 5-HT-evoked changes at molecular, cellular and neuropsychological levels might interact to alleviate the symptoms of clinical depression.