Antidepressants and brain monoaminergic systems: a dimensional approach to understanding their behavioural effects in depression and anxiety disorders

There is extensive comorbidity between depression and anxiety disorders. Dimensional psychiatric and psychometric approaches have suggested that dysregulation of a limited number of behavioural dimensions that cut across diagnostic categories can account for both the shared and unique symptoms of depression and anxiety disorders. Such an approach recognizes that anxiety, the emotional response to stress, is a key element of depression as well as the defining feature of anxiety disorders, and many antidepressants appear to be effective in the treatment of anxiety disorders as well as depression. Therefore, the pharmacological actions of these drugs must account for their efficacy in both. Brain noradrenergic and serotonergic systems, and perhaps to a more limited extent the dopaminergic system, regulate or modulate many of the same behavioural dimensions (e.g. negative or positive affect) that are affected in depression and anxiety disorders, and that are ameliorated by drug treatment. Whereas much recent research has focused on the regulatory effects of antidepressants on synaptic function and cellular proteins, less emphasis has been placed on monoaminergic regulation at a more global systemic level, or how such systemic alterations in monoaminergic function might alleviate the behavioural, cognitive, emotional and physiological manifestations of depression and anxiety disorders. In this review, we discuss how chronic antidepressant treatment might regulate the tonic activity and/or phasic reactivity of brain monoaminergic systems to account for their ability to effectively modify the behavioural dimensions underlying improvement in both depression and anxiety disorders.