6% (13.1-14.2 million adults) In a recent survey.1 According to the World Health Organization’s Global Burden of Disease Report,2 major depression was the fourth leading cause of disease burden worldwide In 1990. The World Health Organization predicts that by 2020, major depression will become the second leading cause of worldwide disease burden, surpassed only by Ischemic

heart disease. In this review, we will focus on major depressive disorder, although we will also briefly discuss bipolar depression. Symptom picture syndrome The cardinal feature of major depression Is PF-02341066 chemical structure persistent depressed mood or pervasive loss of Interest Inhibitors,research,lifescience,medical or pleasure for a minimum of 2 weeks, accompanied by a series of somatic and cognitive changes (Table I). In assessing the core components of depression, it is important to note that the psychological and biological symptoms are accompanied by negative thought content, Inhibitors,research,lifescience,medical cognitive dysfunction, and suicidal ideation. These components follow the American Psychiatric Association Diagnostic Inhibitors,research,lifescience,medical and Statistical Manual of Mental Disorders (DSM-IV) nosology for mood disorders, but recently there has been considerable interest in assessing not only current symptoms,

but also “softer” or spectrum features, which may present lifetime signs Inhibitors,research,lifescience,medical of particular mood or mood-related spectra.3,4 In fact, such persistent features may relate to levels of functional impairment during episodes of depression more directly than current symptoms. Such assessment strategies raise the need for assessment of dimensional approaches to diagnosis, as well as the measurement of traditional categorical distinctions.5 Women are at twice the risk of men. Depression can and often does co-occur with another psychiatric condition or with a medical disease. Depression is a life-threatening illness

for both men and women since suicide is estimated Inhibitors,research,lifescience,medical to be the cause of death in up to 6% of individuals with clinical depression. 6 Table I. Core components of major depression. Pathogenesis and drug targets It has been assumed that the neurobiological systems involved in the pathogenesis almost of depression are primarily the monoaminergic neurotransmitter systems. Considerable research has been directed toward uncovering specific defects in serotonin (5-hydroxytryptamine [5-HT]), norepinephrine (NE), and to a lesser extent dopamine (DA) neurotransmitter systems. The blockade of neurotransmitter receptors or transporters by antidepressant drugs occurs at the level of the neuronal synapse. This capacity to produce acute increases in synaptic levels of monoamines (Table II)7 has been long considered responsible for both therapeutic and adverse effects of antidepressants.