Probing Brain Reward System Function in Major Depressive Disorder

Abstract

THE PATHOPHYSIOLOGY of major depressive disorder (MDD) consists of functional changes in the neurotransmitter and neuroendocrine systems, such as the monoamines and the hypothalamic-pituitary-adrenal axis,^1,2 as well as functional neuroanatomical changes in the cingulate, insula, amygdala, basal ganglia, caudate, and frontal, prefrontal, parietal, and temporal lobes,^3-7 some of which are consistent with postmortem findings.^8,9 Despite evidence of complex neurobiological mechanisms, the therapeutic targets of novel antidepressants remain based on the monoamine hypothesis of depression^10,11 selectively restoring the function of specific monoaminergic systems,¹² without evidence of improved efficacy compared with older classes (eg, tricyclics).¹³