Major depressive disorder (MDD) remains one of the most debilitating psychiatric illnesses worldwide, with an estimated lifetime prevalence of 16% (Kessler et al.,2003). By the year 2020, MDD is predicted to become the second-largest cause of disability after ischemic heart disease, is amongst leading causes of disability-adjusted life years (World Health Organization, 1999), and is associated with lost productivity, physical morbidity, and suicide (Üstün and Chatterji, 2001). Unfortunately, each depressed episode increases the risk for subsequent episodes (Solomon et al., 1997; Mueller et al., 1999). Early identification and diagnosis of MDD is therefore crucial to help target appropriate treatment interventions as early as possible in the illness history for individuals suffering from this debilitating illness.

The recent research agenda for DSM-V has emphasized a need to translate basic and clinical neuroscience research findings into a new classification system for all psychiatric disorders based upon pathophysiologic and etiological processes (Charney and Babich, 2002; Hasler et al., 2004, 2006; Phillips and Frank, 2006). These pathophysiologic processes involve complex relationships between genetic variables, environmental stressors, and abnormalities in neural systems supporting neuropsychological function and behavior, that may be represented as biomarkers of a disorder (e.g. Kraemer et al., 2002), and, in turn, be used to help improve diagnostic accuracy of illnesses such as MDD. Examination of the functional integrity of neural systems supporting key cognitive and emotion processing abnormalities that characterize MDD is therefore a first stage toward identifying biomarkers of MDD.