The role of serotonin in depression and anxiety

Abstract

SummaryThe different coping responses to three types of aversive events - future threats, acute events and chronic stress — may be modulated by 5HT projections. Dysfunction in these coping mechanisms could cause, respectively: generalised anxiety disorder, panic, and depression. This theory proposes that dorsal raphe nucleus projections to 5HT2 and 5HT1D receptors mediate anticipatory anxiety and normally motivate avoidance of threats. The brain aversion system may be held in check by dorsal raphe nucleus 5HT projections to mediate behavioural inhibition during anticipatory anxiety. Proximal aversive stimuli such as pain and asphyxia elicit the fight-flight reflex mediated by the amygdala-hypothalamic-periaqueductal grey brain aversion system. Panic attacks may thus be due to spontaneous activation of this system. Median raphe projections to 5HT1A receptors have been implicated in adaptation to chronic stress-resilence. There is good evidence that 5HT1A function breaks down in depression and causes the depressed state. Experimental tests of this theory suggest that viewing anxiety, panic, and depression as dysfunctions in neurochemically and anatomically specific coping systems is heuristically useful.