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As our knowledge expands and our understanding evolves, we have come to appreciate a confluence between what were previously thought to be independent entities: depression and major medical illness. The associations between depression and medical illness are more intimate and more extensive than previously appreciated. We are beginning to see how the disease processes that overtake the body also affect the brain, and conversely how brain disorders like depression can affect medical illnesses. Depression influences the occurrence, presentation, course, and outcome of many medical illnesses, and conversely, comorbid medical illnesses can affect the onset, presentation, course, and outcome of depression. We owe this enhanced understanding to recent advances in scientific methods, to more precise clinical observation, and to greater diagnostic precision.

Thus the time is ripe for a text based on the premise that depression and medical illness are inextricably bound together and must be viewed through a single lens in order to truly understand them, diagnose them, and treat them. The organization and content of this text are based on this premise. Throughout, we emphasize not simply a critical distillation and balanced summary of the available empirical evidence, but equally important, an active synthesis, formulation, and analysis of that evidence. All of the chapters are authored by the members of our Department of Psychiatry at the Brigham and Women's Hospital, including several who were on our faculty at the time but have since moved to other institutions. In the chapters devoted to specific medical disorders, psychiatrists with particular expertise in those areas have been joined by other eminent Brigham medical specialists or subspecialists. Thus we aim to make these chapters valuable not just for psychiatrists and other mental health professionals, but also for a wide range of medical specialists as well.

The relationships between depression and medical illness are complex; each is in itself multifactorial, and furthermore their interrelationships are bidirectional. Medical illness may cause depression via direct pathophysiological action in the brain, and depression may also result from the psychological and emotional response to the stress, physical suffering, and disability imposed by the medical illness. Depression may also be caused by the medications used to treat the medical illness. Conversely, depression may lead to or exacerbate a co-occurring medical illness, via biological and/or behavioral mechanisms. In addition, antidepressant pharmacotherapy and somatic treatments for depression have systemic effects and can thereby exacerbate medical illness. Finally, both depression and medical illness may co-occur because they can both result from the same underlying pathophysiological process, for example, inflammation, or from the same neurobehavioral risk factors, such as alcoholism.

The book is organized in five sections. The first two chapters provide a conceptual and intellectual framework for understanding depressive illness. In chapter 1, we clarify the use of the term depression, since it can refer both categorically to a diagnosable disorder as well as dimensionally to symptoms (affective, cognitive, behavioral, and somatic) that exist along a spectrum of severity. Particular attention is given here and throughout the text to the clinical, epidemiological, and neurobiological overlap of depression and anxiety. Chapter 2 goes on to address the neurobiology of depression, considering systems-level, cellular, molecular, genetic, and epigenetic factors, including what we know about the neurocircuitry and neurochemistry of the disorder, as well as the findings emerging from structural and functional neuroimaging.

In Section 2, Chapters 3 and 4 discuss the general principles of depression diagnosis and treatment. Here and throughout the book, we emphasize the importance of diagnostic precision, screening, early intervention, measurement-based care, the individualization of treatment, and collaborative care. The discussion of diagnosis attends to boundary issues (e.g., with anxiety), the clinical interview, screening and the use of rating scales, the assessment of suicide, and special cross cultural and ethnic considerations in diagnosis. Chapter 4 begins with a general approach to the patient and goes on to discuss specific considerations imposed on depression treatment by the concurrent presence of medical illness. Pharmacotherapies and the most recent somatic therapies are discussed, along with the psychotherapies for which there is evidence of efficacy in the medically ill.

The chapters in Section 3 carefully, comprehensively, and critically assess what we know about depression when it is comorbid with the full range of major medical disorders, including sleep disorders and substance use disorders. The focus is on those particular aspects of depression that are specific and unique when it occurs in medically ill patients. Each chapter follows the same format: epidemiology; pathophysiology; clinical presentation; course and natural history; assessment and differential diagnosis; and treatment. When there is insufficient empirical evidence, we discuss the limits of what is known and suggest guidelines for proceeding, given the current state of our knowledge. We pay particular attention to the phenomenology of the medical illness and of depression, the course of untreated and treated depression when co-occurring with the medical illness, the impact of depression on the course of the medical illness, and of the effect of medical illness on the course of the depression. These chapters focus on the aspects of depression assessment and treatment that are unique to the particular medical illness being considered: What is the pathophysiology of the relationship? How treatment-responsive or treatment-refractory is depression when it is associated with this particular medical illness? What are the depressive side effects of medications used to treat these medical conditions? What are the effects of antidepressants on the medical illness?

Section 4 is devoted to special patient populations and the importance of the settings in which care is delivered. Here we address issues specific to the medically ill child who is depressed and the elderly medical patient who is depressed. The final chapters in this section discuss particular issues that arise in the settings in which the depression care is delivered, including the care of the surgical patient, collaborative care in ambulatory medical practices, the emergency department, and the depressed medical inpatient.

The book concludes with a glimpse into the future. We are moving toward greater understanding of the final common pathways mediating depressive symptoms and medical illnesses, and toward a more complete understanding of the relevant neurophysiological and pathophysiological processes. We look forward to the development of multimodal biomarkers that will lead to targeted therapies and more precise and individualized treatment planning. We will also witness a more seamless integration of depression care into general medical care, greater diagnostic precision, and earlier identification and intervention. We are entering a truly promising era in the understanding and the care of medically ill patients who are depressed.

Arthur Barsky, MD

David Silbersweig, MD

Boston, Massachusetts

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