This book addresses one of the fundamental questions in the etiology of depression: Does stress cause depression? Although intuitively one may answer yes to this question, the book presents detailed psychological and neurobiological evidence to show the complexity of the issue. The book focuses on three major themes: (1) pathophysiology of stress in depression; (2) stress-inducible subtypes of depression; and (3) diagnosing depression to understand biological underpinnings of the condition. Although each of the three authors wrote individual chapters (with van Praag writing most chapters), the book is well organized and flows smoothly. The book is well written in an entertaining style, especially the chapters written by van Praag. For example, when discussing the problems with the current DSM-IV diagnostic system, van Praag states, “psychiatric diagnosing is locked up in a nosological straightjacket, and thus immobilized” (p. 8). It is this type of commentary, sprinkled throughout the book, that holds the reader's interest. In addition, the authors provide a fresh perspective on diagnostic issues in depression, stress/negative life events, and the neurobiology of depression. I expect the volume will stimulate research ideas. To get the most out of the book, it should be read in its entirety. Exceptions are the chapters reviewing the psychobiology of stress and depression, which provide very comprehensive summaries of the research literature, and may serve as a good reference. The initial chapters build the theoretical foundation for the presentation of the biological data, and the final chapters integrate the biological data with the initial hypotheses. The authors take issue with diagnostic trends in psychiatry, definitions of stress and life events, and to a lesser extent, neurobiological approaches to psychiatric research. The authors do not rehash old findings, but include the most recent literature. For example, when discussing corticotrophin releasing hormone (CRH) receptors, they present new findings supporting a possible parallel parasympathetic-related system in addition to the traditional sympathetic response. When the data presentation becomes complex, information is summarized in easy-to-read tables.

Chapter 1 discusses the diagnosis of depression, providing an argument against the current nosological approach used in the DSM-IV system. The authors argue for a sophisticated diagnostic methodology (i.e., multi-tier diagnosing) that includes nosological cluster, syndromal analysis, symptom analysis, psychic dysfunction underlying symptoms, symptom severity, course and duration, personality features, and functional effects of the symptoms. The multi-tiered approach is shown to have relevance to treatment as well as study of the neurobiology of depression.

Chapter 2 presents an introduction to traumatic life events. The authors provide a brief history of the study of stress and how stress has been handled by the different psychiatric diagnostic systems. Definitions of stress and coping are also discussed. There is an interesting section on the interaction between personality structure and life events. Chapter 3 then goes on to discuss basic issues related to traumatic life events and depression. The authors highlight, for example, how there is confusion in the literature between distress and depression. They offer a definition of life events and describe the heterogeneity of events themselves, as well as their consequences. Again, the authors offer a unique prospective, arguing that much of the research on the impact of life events on mood state has been “de-subjective.” They suggest a research approach that includes an experiential perspective that captures the heterogeneous response to stress.

Chapter 4 explores the causal connection between traumatic life events and depression. Data are presented that support the increased risk for depression in individuals exposed to negative life events. The authors again emphasize the role of personality characteristics in the interaction between stress and depression. They also discuss very interesting stress-vulnerability models. Chapter 5 begins with a nice review of genetic concepts and types of genetic research. They go on to summarize the family, twin, and adoption study findings. The authors allude to molecular genetic studies, but spend little time discussing the difficulty with these types of studies in depression. After reviewing this literature, the authors suggest that gene–environment interactions are clearly more important than either factor alone. Chapter 6 deals with the correlation and interaction between genes and environment in depression, termed ecogenetics. The authors spend most of the chapter discussing differences between synergistic, parallel, and multiplicative models. The little available data are presented to highlight the importance of gene–environment interactions in the expression of depression.

Chapters 7 and 8 make up the bulk of the book. These chapters present (in great detail) the history and research findings of the two major biological research domains on the etiology of depression. The chapters are dense with research findings, but the authors do a very good job summarizing within sections and bulleting key concepts. Chapter 7 discusses the monoamine hypothesis. For each neurotransmitter system (i.e., serotonin, noradrenaline, dopamine), the authors describe location of circuits in the brain, as well as receptor sites. In addition, relevant animal work and human findings are summarized. Behavioral correlates of monoamine disturbances in depression are discussed and lead to an interesting discussion about affiliation and aggression in the animal literature. In Chapter 8, the authors extensively review the role of stress hormones in depression. Important concepts such as homeostasis and allostasis are presented. The hypothalamic-pituitary-adrenal (HPA) axis is carefully reviewed and the complex literature is presented, including the role of CRH and cortisol. The reader comes away from the discussion appreciating the heterogeneity of the stress response, as well as the potentially powerful effects of the HPA system on brain structure and function. Interesting clinical data on the interaction between early life stress, the HPA axis, and structural brain changes are presented. The authors complete the discussion by linking the HPA axis with functioning of the monoamine system.

The final chapter (Chapter 9) is the title chapter of the book, in which the authors combine their previous discussions and present an argument that certain forms of depression are associated with the stressed state. To support their argument, they discuss comorbidity between depression, anxiety, and aggression, as well as an interesting depressive syndrome involving reversed vegetative symptoms. They indicate how anxiety/aggression may be the “pacemaker symptoms” of certain forms of depression. They use anxiety/aggression-driven depression as a model disorder that emphasizes “functionalization” (i.e., psychic disturbance rather than disease entity) and “verticalization” (i.e., attempting to distinguish symptoms directly related to the neurobiological substratum).

Overall, this is a valuable book for clinicians, researchers, and students interested in the neurobiological underpinnings of stress, negative life events, and depression. The writing style is engaging, and the authors present a point of view that challenges standard practice of psychiatric diagnosis and research.