Abstract
Unipolar depressive disorder, also known as major depressive disorder, is a heterogeneous, environmentally influenced, and genetically complex psychiatric disorder with profound societal impact. Patients with major depressive disorder have increased risk for comorbid psychiatric disorders including anxiety disorders, posttraumatic stress disorder, obsessive-compulsive disorder, and substance use disorders, as well as medical disorders such as diabetes, cardiovascular and cerebrovascular disease, and cancer. Historically, translational and clinical research into the pathogenesis of major depressive disorder and its response to treatment focused on the monoaminergic neurotransmitter systems. Observations of the clinical and biological features of depression in patients with endocrine disorders affecting the adrenal cortex and thyroid gland, patients with autoimmune disorders, and patients treated with medications impacting immune function substantially broadened the scope of theoretical conceptualizations for the etiology, or rather etiologies, of depression. Ultimately, a central goal of research into depressive disorders is the identification of genetic and peripheral blood-based or brain imaging biomarkers of risk and/or response to treatment. The identification of such markers has the potential to greatly shorten the time to diagnosis and optimize early and personalized selection of maximally effective treatments and may also point to, as yet undiscovered, treatment targets.