HELEN S. MAYBERG
Depression is one of the most common of all psychiatric disorders and is a leading cause of disability worldwide. Current psychiatric tenets assume a core biological basis for this condition; however the disorder continues to be clinically defined by patient self-report, with treatments generally prescribed without consideration of etiology or pathophysiology. As presented in the following state-of-the-art chapters, there has been tremendous progress toward defining a comprehensive multidimensional neurobiology of mood disorders. The authors in this section provide critical perspective on recent basic, translational, and clinical research advances contributing to an evolving integrative understanding of illness risk and vulnerability, molecular and circuit pathophysiology, and novel diagnostic and treatment strategies.
The section opens with a comprehensive review by Fawcett and Hager of the history and changing nosology of depression diagnosis. This chapter provides broad perspective on the potential changes in the clinical research landscape anticipated by the introduction of DSM-5 (Chapter 29), as well as the need for improved clinical characterization of depression subtypes and syndromic dimensions to fully define mechanisms and develop and test novel treatments. Levinson next present an update on the genetics of depression, summarizing the challenges, limitations, and potential of various approaches including candidate gene studies, genomewide association studies, and evolving applications of sequencing and stem cell technologies (Chapter 30).
Hodes and Russo follow with a critique of the theoretical and practical applications of a wide range of genetic, developmental, and stress-based animal models currently in use to study depression. This chapter provides a comprehensive summary of behavioral endophenotypes and associated peripheral and central biomarkers and behavioral assays relevant to the human condition (Chapter 31).
Duman (Chapter 32) and Furey, Mathews, and Zarate (Chapter 33) offer complementary basic and clinical perspectives on molecular and cellular mechanisms contributing to depression pathogenesis and treatment response with a particular emphasis on their role in development and clinical testing of a new generation of rapid-acting antidepressant agents. Price and Drevets provide important anatomical context to such molecular and cellular findings in their comprehensive review of brain circuits implicated in depression and mood regulation covering basic anatomy, structural and functional neuroimaging, and postmortem pathological studies (Chapter 34).
Krishnan (Chapter 35) extends the discussion of the neuroanatomy of depression to a late-life perspective highlighting vascular pathophysiology and both postmortem and imaging studies of depression in the elderly. Rubinow, Schmidt, and Craft (Chapter 36) focus on the role of gonadal steroids and mood disorders with a comprehensive review of cellular mechanisms, clinical syndromes, and treatment mechanisms. Benton, Blume, Crits-Christoph, Dubeé, and Evans next provide an updated perspective on depression and medical illness (Chapter 37) emphasizing studies of cardiac disease, diabetes, HIV/AIDS, and cancer. The section concludes with comprehensive summary of depression treatments by Iosifescu, Murrough, and Charney (Chapter 38), presenting an overview of treatment efficacy, side effects, and mechanisms of action of the major classes of available interventions and discussing new research on predictive biomarkers and advances in novel treatment development.
Clearly, considerable progress has occurred since publication of the last edition. Judging from this set of comprehensive reviews, the field appears poised for disruptive new advances impacting diagnosis, evidence-based treatment development, and, ultimately, improved care of patients with this common and disabling disorder.
DISCLOSURE
Dr. Mayberg has a consulting agreement with St. Jude Medical Neuromodulation, which has licensed her intellectual property to develop SCC DBS for the treatment of severe depression (US 2005/0033379A1).