Reduced Brain Norepinephrine and Dopamine Release in Treatment-Refractory Depressive Illness

Abstract

THE DEBILITATING symptoms that accompany bouts of depressive illness are presumed to arise, at least in part, because of an aberration in brain monoamine neuronal activity. The effectiveness of certain antidepressant medications, such as norepinephrine uptake–blocking agents, formed the foundation for the catecholamine deficiency hypothesis of affective disorders.¹ The observation that a substantial proportion of patients with depression fail to respond to available medications suggests that it is implausible to ascribe the symptoms of depression merely in terms of abnormal brain noradrenergic neuronal activity. Niklasson and Ågren² have documented weak monoaminergic neurotransmission in patients with depression and have demonstrated an association between diminished brain monoaminergic function and reduced cerebral metabolism.