Overview of the field

Clinical descriptions of depression date back to antiquity. Scientific investigations of mood disorders started only 150 years ago. An historical overview of depression leads into today's knowledge that depressive disorders are common, serious, and sometimes life-threatening and that their effects are persistent and costly. Depressive disorders have a high prevalence, around 5% in the general population, with at least 20% of patients suffering with chronic conditions, such as cardiovascular disease and diabetes. Neuroimaging technology provides unprecedented opportunities for elucidating the neurobiological correlates of mood disorders. Neuroimaging studies of primary mood disorders have identified neurophysiologic abnormalities in the orbital and medial prefrontal cortex (PFC), the amygdala, and the related parts of the striatum and thalamus. There has been a revolution in our understanding of the pathogenesis of depression, with recent work demonstrating, among others, the critical impact of stress. There is an abundant evidence from family, twin, and adoption studies that genetic factors play an important role in the etiology of affective disorders. A variety of hormonal abnormalities, such as altered levels of cortisol, growth hormone, or thyroid hormones, indicate the existence of endoctrine disturbances. Despite the initial findings of immunosuppresion in depression, some studies have indicated that immune activation could also be present and might even play a role in the onset of depressive symptoms. Neurotrophic factors are among the growth factors that have been studied for their role in the adult nervous system. Despite advances in the pharmacotherapy of depression, only one third of patients respond favorably to antidepressant drugs. One third do not respond at all, and in clinical trials, at least one third respond to placebo. There is clearly an urgent need for novel antidepressants.