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Depression and Brain Dysfunction
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     Because we still do not know very much about the causes or the mechanisms of expression of the major psychiatric disorders, analogy may have substantial utility. Depression and Brain Dysfunction is a book of analogies devoted largely to examining mood disorders that occur in the context of neurologic diseases; its intent is to teach us about biologic mechanisms of idiopathic ("primary") depression.

    I believe that there are four important questions about developmental neurobiology that must be answered in considering psychiatric conditions: How are we wired? How do learning, environment, experience, and powerful life events change brain function? How do we maintain homeostatic balance? How do we "fall apart" in the end? Each of these questions provides a challenge for understanding depression. Clinically significant depression can occur at nearly any point in life; it can be "endogenous," with a powerful autonomous quality that is seemingly independent of life events, or it can be "reactive" in the face of traumatic events, even among those who have never shown signs of mood instability. It can be especially prevalent in some families, apparently reflecting genetic influences, and it can occur without familial patterns. Emergent mood disorders are common later in life, though they may not be typical of midlife patterns of expression; the same holds true for depression that develops in adolescence. Comorbidity is the rule, though the nature of the comorbidity changes during life, and this may have implications for the cause of depression.

    With this background in mind, one can ask whether Gilliam and his coeditors have succeeded in their book. The opening chapters are thoughtful reviews of the classification of depression and its presumed or suspected neurobiologic substrates. There are pertinent discussions of the findings of imaging methods that point to suspected anatomical underpinnings. But the editors do not take the opportunity to use these discussions to frame the central chapters that make up the bulk of the book — those detailing the prevalence of, the presentations and distinctive features of, and treatments for the kinds of depression that occur in the context of specific neurologic disorders.

    The editors have not, for example, systematically integrated idiopathic depressive conditions with similar states that seem closely associated with — or may even be "due to" — brain disease. These comparisons between what we know and what we do not know are never developed. Although the main chapters dealing with depression in the context of different neurologic diseases are sound, they are not exciting, nor are they essentially different from what would be expected in a competent textbook.

    Despite the inclusion of careful discussions of findings concerning stress hormones in idiopathic depression, the editors have failed to include endocrinopathies as an analogy, which would have raised the question of neurohumoral mechanisms. Another concern is that "depression" is not a single entity. Depressions vary in presentation, course, and family history, and these elements are influenced by the age at onset and developmental timing (e.g., during pregnancy, post partum, or during menopause), sex, life events, and cultural contexts.

    Confidently identifying the origins and mechanisms of depressions remains a challenge. Depressions are multidetermined conditions about which an understanding of brain processes is necessary but not sufficient in itself. And even when our focus is on the brain, we tend to be simplistic, our lens narrowed both by the limits of current research technologies and by our tendency for reductionist thinking.

    Eric D. Caine, M.D.

    University of Rochester Medical Center

    Rochester, NY 14618

    eric_caine@urmc.rochester.edu(Edited by Frank G. Gillia)