Depression and 5HT.

5HT has been implicated in mechanisms of anxiety and depression for many years but the evidence is contradictory. Perhaps one error has been to think of 5HT as a unitary system when in reality it is highly differentiated. There has been an explosive increase in knowledge about different 5HT receptor subtypes and it has long been known that there are different anatomical subsystems. Evidence will be summarised that the different systems subserve different psychological functions and that dysfunction in the different systems results in depression, anxiety, panic and OCD in an understandable way. Much evidence is compatible with the idea that 5HT systems reduce the impact of impending or actual aversive events. Anticipation of an aversive event is associated with anxiety and this motivates avoidance behaviour--a normal adaptive response. There is evidence that this is mediated by projections of the dorsal raphe nucleus and associated 5HT2 and 5HT3 receptors. Projections of the median raphe nucleus and associated 5HT1A receptors appear to mediate resilience to aversive events once they have occurred or if they persist. When this system breaks down depression results. It will be argued that all effective antidepressants act on 5HT1A, natural mechanisms of resilience.