Opioid modulation of depression: A focus on imaging studies.

Depression is the leading cause of disability worldwide, with over 300 million people affected. Almost all currently available antidepressant treatments target monoamine neurotransmitter systems and have a delayed onset of action up to several weeks that can be associated with low rates of treatment response. The endogenous opioid system has been identified as a potential target for the development of novel antidepressants due to its high opioid receptor concentrations in central limbic areas that are also implicated in physiological processes including regulation of mood and emotion. Genetic depletion, pharmacological manipulation, and preclinical models have been widely used to characterize the role of opioid transmission in depressive states. Neuroimaging studies have been carried out in clinical populations to investigate opioid transmission in mood and emotion in an attempt to identify those regional anatomical and functional brain changes that are associated with depression. Great insight has been provided into the cerebral structural and functional changes associated with depression but there remains a need to tie the functional theories of depression to anatomical localization and further neuroimaging studies are best placed to do this.