Using functional neuroimaging to investigate the mechanisms of action of selective serotonin reuptake inhibitors (SSRIs).

Selective serotonin reuptake inhibitors (SSRIs) are effective in the treatment of depression and a range of anxiety disorders [1;2]. Preclinical models have been relatively successful at elucidating the key neurochemical effects of these serotonergic agents; however, a lack of understanding exists of the functional mechanisms by which these drugs exert their effects on mood and anxiety. Elucidating the link between the neurochemical effects of these drugs and their therapeutic action is an essential step in further understanding some of the current limitations of SSRIs, and in developing novel agents that are more selectively designed to target the symptoms they treat. An increasingly popular experimental method within psychopharmacological research is the use of functional neuroimaging techniques to investigate the pharmacological modulation of task-induced brain activity by psychoactive drugs. Such an approach offers an exciting opportunity to investigate the mechanisms of drug action and, in this way, bridge the gap between preclinical and clinical studies. Applying this approach to the study of SSRIs has highlighted that direct modulation of activity in neural areas involved in emotional processing may represent a key functional mechanism through which these agents exert their antidepressant clinical effects. This review summarises the cognitive and neuroimaging evidence suggesting the critical role that disruptions in emotion-related processing play in depression and anxiety disorders. It then examines the functional neuroimaging evidence, from both patient and healthy volunteer studies, to suggest that the amelioration of such disruptions is a key mechanism through which SSRIs exert their therapeutic effects