Selected abbreviations and acronyms α2-AR α2-adrenoceptor β-AR β-adrenoceptor DAT dopamine transporter GPCR G protein-coupled receptor 5-HT 5-hydroxytryptamine (serotonin) LC locus ceruleus Notes The contributions of former and current members of the Clinical Neurobiology Laboratory at the German Primate Center are gratefully acknowledged. The work summarized here was in part supported by the German Science Foundation, the DAAD, and the EC.
Depression is a common, chronic, and often disabling psychiatric illness, which is estimated to affect 5% to 10% of the population. It frequently appears Inhibitors,research,lifescience,medical in early life, has a

chronic course, and is considered a risk factor for other medical illnesses, such as coronary vascular disease, diabetes, and osteoporosis. This is not altogether

surprising given the extensive bidirectional “mind-body” interactions mediated Inhibitors,research,lifescience,medical via the autonomic nervous system, immune system, and a host of neuroendocrine factors. According to the World Health Organization (WHO), depression is the leading global cause of years of life lived with disability and the fourth leading cause of disability-adjusted Inhibitors,research,lifescience,medical life-years. Disability-adjusted life-years is defined as the reduction in an individual’s productive life, and takes into account premature mortality.1,2 Considering the high morbidity and mortality associated with depression, it is unfortunate that the psychological and neurobiological underpinnings of depression have not been specifically defined. Although major depression is currently diagnosed by means of a diagnostic system (Diagnostic and Statistical Manual of Mental Health Disorders, Fourth Edition [DSM-IV]) based upon phenomenology, Inhibitors,research,lifescience,medical this disorder most likely embodies a heterogeneous set of disorders with multiple causes. Therefore, one of the major goals of current, and future selleck research on depression is the development of a diagnostic system Inhibitors,research,lifescience,medical based on etiology.3 This goal

is becoming increasingly closer to reality due to recent progress in the identification of neural circuits, neurochemicals, and signal transduction mechanisms underlying the pathophysiology and treatment of depressive illness.4,5 Advances toward specifying the contribution of genetic factors,6 psychosocial stressors,7,8 and gene-environment interactions those to susceptibility to depression are also taking place.9,10 It is anticipated that, in the next few years, combined use of genomic and proteomic strategies to refine complex psychiatric diseases into mechanism-based subcategories may ultimately facilitate the matching of specific target-based therapies to particular markers in certain patient subgroups.11 Of all brain systems, the monoaminergic neurotransmitter systems have received the greatest attention in neurobiological studies of depressive disorders.