Etiology of Depression: Genetic and Environmental Factors Radu V. Saveanu, MD a, *, Charles B. Nemeroff, MD, PhD b KEYWORDS • Trauma • Genes • Environment • Depression Major depression is a common disorder, accounting for more disability than any other disorder worldwide. The rates of major depression in the United States rose markedly in the decade from 1991 to 2001, from 3.33% to 7.06%. 1 This increase is of considerable consequence, because depression is associated with significant mor- bidity, disability, increased medical comorbidities, and mortality. 2 It is the most significant risk factor for suicide, a leading cause of death worldwide, especially in adolescents, young adults, and the elderly. Despite the prevalence and costly consequences of depression, there are still no validated, diagnostically useful biological tests to aid in the diagnosis of this disorder and very few that predict a response to established and effective treatments. Similarly, although some promising candidates are emerging, there are no biomark- ers, such as alteration in gene expression or tumor marker, that are associated with improvement with antidepressant or psychotherapeutic treatments. Of considerable concern is the recent realization, stemming from several large- scale treatment studies, that the efficacy and effectiveness of currently available antidepressants and psychotherapy are unacceptably low (eg, STAR*D). 3 Dr Saveanu has indicated financial relationships with Novartis, Brain Resources, Inc (grants/ research support). Dr Nemeroff has indicated financial relationships with American Foundation for Suicide Prevention (AFSP), NovaDel Pharma (board of directors); Xhale, Tadeka (consultant); NIH, Agency for Healthcare Research and Quality (grants/research support); CeNeRx Bio Pharma, PharmaNeuroBoost (other financial interests); AFSP, CeNeRx Bio Pharma, National Alliance for Research on Schizophrenia and Depression, NovaDel Pharma, PharmaNeuroBoost, Anx- iety Disorders Associate of America (scientific advisory boards); CeNeRx Bio Pharma, Concept Therapeutics, NovaDel Pharma, PharmaNeuroBoost, Revaax Pharma, Xhale (stockholder). a Department of Psychiatry and Behavioral Sciences, Leonard M. Miller School of Medicine, University of Miami, 1695 Northwest 9th Avenue, #3100, Miami, FL 33136, USA b Department of Psychiatry and Behavioral Sciences, Leonard M. Miller School of Medicine, University of Miami, 1120 Northwest 14th Street, Suite 1455, Miami, FL 33136, USA * Corresponding author. E-mail address: rsaveanu@med.miami.edu Psychiatr Clin N Am 35 (2012) 51–71 doi:10.1016/j.psc.2011.12.001 psych.theclinics.com 0193-953X/12/$ – see front matter © 2012 Elsevier Inc. All rights reserved.