AGAINST DEPRESSION

By Peter D. Kramer. Viking. 353 pp. $25.95

Our society doesn't quite know how to think about the emotional life of human beings.

On the one hand, we are willing -- indeed, eager -- to own our emotions (or, if necessary, manufacture them) in a way inconceivable 30 or 40 years ago. Presidents shed tears in public. You no longer have to be a therapist to ask a stranger to describe his feelings. Sites of tragedy become teddy-bear-strewn shrines overnight, paying homage as much to visitors' emotions as to the victims' memory.

On the other hand, we are more inclined to view those emotions -- unhappiness, anxiety, desire, contentment -- as the product of neural circuits only somewhat connected to our day-to-day experiences. Millions of us are eager to try to adjust our "brain chemicals" with prescription medicines.

The condition sitting most directly astride this ambivalence is depression. We think of depression as illness, diagnose it liberally and increasingly treat it without embarrassment. (Antidepressants last year were the fourth-leading class of prescription drugs sold in the United States). But we're also infatuated with the lore, narrative, danger and even dark romance of the ailment. Depression is a disease built of materials -- sadness, guilt, shame, exhaustion -- we all know personally. That can't be said of diseases like diabetes. Who relates in the same way to his own insulin, as essential as it is for life? That's why there are bestsellers named Darkness Visible but none called Hyperglycemia Sensible.

In his new book, Peter D. Kramer examines depression with a cool, intelligent and sympathetic eye. The author of the wildly popular Listening to Prozac, he is a practicing psychiatrist who sees depression and its human cost nearly every working day. He asks two interesting questions: If we could eradicate depression, would we? And if we did, would we lose anything of value?

Kramer's view is unambiguous: The more we can prevent depression, the better. And no, we won't lose much if depression becomes like tuberculosis, a disease that 150 years ago also had its own culture, romance and meaning -- all of which crumpled under the power of medicinal chemistry. Today (in this country at least), TB is extremely rare and entirely unmissed.

Kramer sets up his argument with several long, insightful anecdotes from his practice. To give just one example, he describes how he learned to stop probing and interpreting depressed patients' symptoms, as a psychoanalyst might. He tried to get one woman to examine her guilt and feelings of indifference to others. He assumed that those emotions (and the behavior that arose from them) were part of her "core personality" as well as symptoms of the disorder. When she recovered from her depression, she was indignant that Kramer had assumed that any part of the illness also expressed the "real" her. "She wanted to know why, in our discussions, I had granted an impostor -- the depression -- such standing," Kramer writes. "I had been negotiating with an occupying government, of Margaret's mind, while the legitimate ruler was in exile."

It's all disease, just plain disease, Kramer argues. How is he so sure? He takes the reader on a tour of what's happening at the level of brain and neuron.

Depression appears to cause cell loss in the prefrontal cortex, the seat of emotion and cognition. It also shrinks the hippocampus, a more ancient structure involved in memory formation. The chronic overexposure to stress hormones, some produced in the adrenal glands, appears to be the toxic event. These brain structures also lose much of their capacity for regeneration, which leaves them more vulnerable after each bout of illness.

In truth, the "morbid anatomy" of depression (and all other psychiatric disorders) is largely unknown. The studies that find brain abnormalities in depressed people all have small sample sizes -- irresponsibly small, in my opinion -- which make their findings tentative and hard to evaluate. Further, there are always huge overlaps among the individual members in the "normal" and "diseased" groups, even if the average measurement of each group is different. The exact location in the brain of depression's activity is also less informative than Kramer lets on. To say something is going on in the prefrontal cortex is a bit like saying something is going on in New England -- it doesn't narrow things down much.

Nevertheless, there's little doubt that depression is a disease with physical workings, just like cancer, asthma and osteoporosis. But how is it also tied to experience? Why do people usually become depressed after real events that are, well, depressing?

This is the key question, and Kramer does not shrink from it. He provides a subtle, closely argued explanation, drawing heavily on a study of twins by behavioral geneticist Kenneth Kendler, which suggests that certain personality traits with strong genetic origins raise a person's risk for depression. Specific experiences, child sexual abuse first among them, also strongly increase risk. However, neither genes nor events condemn a person to depression. Instead, each sets a trajectory that bad luck, bad experience and the cumulative brain damage resulting from extremely dark moods can magnify, carrying a person away from health.

"The genes create adverse environments, as when they lead to a temperament that the culture fails to reward," Kramer writes. "Ordinary environments become adverse when interpreted through personality shaped by the genes, as when a person needs more social stability and predictability than the culture tends to provide. Outcomes that evolve on this mixed basis in time affect which transmitters are and are not expressed in the brain, which receptors for those transmitters are protected, which cells flourish and which atrophy. Genes and environment interact at every level -- behavior, feeling, chemistry, and anatomy."

As you can see, it can get pretty dense. But it's also pretty interesting. And let it be said: There are no straw men in Against Depression. Kramer gives the arguments against his "medical" view of depression full muscle and wrestles them with admirable exertion and impressive skill.

A point that Kramer makes repeatedly is that the opposite of depression isn't happiness. It's resilience. It's not the absence of guilt, sadness and alienation but the ability to find a route away from those feelings in due time.

Kramer ends the book with a discussion of the role depression plays in setting literary taste. In a word, he thinks melancholy is overvalued. He submits, as one example, John Updike, whose immense accomplishment is underappreciated because he isn't melancholic enough and in whose writing "wonder at the world's riches is never absent." (I agree.) At the moment "heroic melancholy persists in art," he writes, although he thinks "perhaps it will fade in the face of improvements in treatment."

He is more certain that, as science chips away at the mechanism and causes of depression, the disease will become smaller in our eyes. Its likely disappearance in the face of medical advances won't desensitize us to tragedy and sorrow. In fact, he believes, it will help many people preserve memory, feel deeply and respond passionately: "We should have no trouble imagining resilience that contains as much depth as any ever attributed to depression."

The funny -- and slightly scary -- thing is we may actually get to see whether he's right. *

David Brown is a science writer for The Washington Post.