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What is depression? Anyone who has dealt with the condition knows what it can feel like — but what causes it, what sustains it, and what’s the best way to make it subside?

Despite the prevalence of the disorder — in one Centers for Disease Control and Prevention study, 9.1 percent of adults met the criteria for depression — experts haven’t fully answered these questions. And to fully do so, some say we need new ways of thinking about depression entirely.

For Turhan Canli, a professor of integrative neuroscience at Stony Brook University, that means looking at the possibility that depression could be caused by an infection.

“I’ve always been struck by the fact that the treatment options did not seem to have dramatically improved over the course of decades,” Dr. Canli told Op-Talk. “I always had a feeling that somehow we seem to be missing the actual treatment of the disease.”

He was intrigued by research showing a connection between depression and inflammation in the body, and he started to think about the known causes of inflammation — among them pathogens like bacteria, viruses and parasites.

In a paper published in the journal Biology of Mood and Anxiety Disorders, he lays out his case for rethinking depression as a response to infection. He notes that the symptoms of depression are similar to those of infection: “Patients experience loss of energy; they commonly have difficulty getting out of bed and lose interest in the world around them. Although our Western conceptualization puts affective symptoms front-and-center, non-Western patients who meet DSM criteria for major depression report primarily somatic symptoms.”

And, he writes, we already know that infectious agents can affect our emotions — he points to Toxoplasma gondii, a parasite that’s now somewhat famous (at least among science lovers) for its striking impact on its hosts. T. gondii can make rats like the scent of cat urine (causing obvious problems for the rats). In humans, it may have serious psychological effects — Dr. Canli cites research linking T. gondii with suicide. “Yet,” he writes, “large-scale studies of major depression and T. gondii or systematic searches to discover other potential parasitic infections have not yet been conducted.”

He believes researchers should compare tissue samples from depressed patients with those from non-depressed people, looking for evidence both of known pathogens and of new ones.

If successful, such a search could bring about big changes in depression treatment. “Imagine if we had identified one or multiple pathogens that all are associated with major depression,” Dr. Canli said. “That could mean that at some point in the future a patient would present himself or herself at the doctor’s office and the first thing they would do is run a workup on the blood or stool sample to identify exactly which particular pathogens might be present, and then develop a very targeted treatment program to address exactly those.”

One day, he suggests in his paper, research into infection and depression could even lead to a vaccine.

“I think if we are open to new ideas and research approaches we should have a good chance” of developing much better treatments for depression, he told Op-Talk. “I’m less hopeful that staying with the status quo is necessarily the way to go.” Understanding how depression really works, for him, is key: “I think we should try to really be innovative about discovering mechanisms. Once we can get at the mechanisms, I feel much more hopeful.”

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PAUL W. ANDREWS, A PROFESSOR of evolutionary psychology at McMaster University, looks at depression from a different angle. His research looks at rumination, which he defines as “intense, persistent, intrusive, distraction-resistant thoughts.” Such thoughts are common in depression, and they’re generally thought of as a bad thing. But Dr. Andrews thinks rumination could be an adaptation — something humans developed to help them solve complex problems.

In particular, rumination’s power to override distraction may be important. Ordinarily, he told Op-Talk, analytical thinking requires a lot of working memory — if you need to solve a complex math problem in your head, for instance, “you have to solve it in steps, and then as you’re going through the steps you have to keep track of the stuff that you’ve already figured out, and you have to remember the stuff that you still need to do.” And the more stuff you have to keep track of, the more likely you are to get distracted.

But what if rumination keeps you focused, fending off distractions until the problem is solved? “The distraction-resistant nature of rumination could be extremely useful if what you’re trying to do is analyze a complex problem in your life,” he explained. “If depression helps you reduce your distractibility, that could really facilitate the quality of your analysis.”

Dr. Andrews and his colleagues Skye P. Barbic and Zachary Durisko have created a scale for measuring and evaluating rumination that they call the Analytical Rumination Questionnaire. In a paper published in PLoS One, they note that the scale looks at four different types of analytical rumination: “(1) understanding the cause (e.g., ‘I tried to understand why I had these problems’); (2) understanding the aspects of the problems that need to be solved (e.g., ‘I tried to understand what was wrong in my life’); (3) generating possible solutions (e.g., ‘I thought about all my options for dealing with my problems’); and (4) evaluating the advantages and disadvantages of possible solutions (e.g., ‘I thought about whether my options for dealing with one problem would make other problems worse’).”

These types can also be understood as steps in a process, said Dr. Andrews: “You need to understand why the problem occurred and what needs to get solved before you can start generating solutions and evaluating them.” And a way of measuring this process might help clinicians fine-tune their therapy: “Our scale can help identify where people are at in this pathway of analysis,” he explained, “and if a physician or psychiatrist sees they’re stuck at one point,” then he or she can focus the therapy on that aspect of the patient’s problem. Dr. Andrews also thinks developing such targeted therapies could help clinicians reduce their reliance on medications, many of which come with side effects.

He doesn’t believe all cases of depression are triggered by problems that need to be solved. “Depression is not like a single trait,” he said. “It’s really a series of multiple traits that have in common sadness and anhedonia.” But, he added, research shows that many people with depression can point to troubles that they believe brought it on.

And if in fact depression is at least in part an adaptation meant to help us deal with difficult problems, he thinks this could have big implications for the way we diagnose it. The Diagnostic and Statistical Manual of Mental Disorders, he said, “essentially imposes arbitrary thresholds on the depressive continuum.” But understanding how mental processes are actually supposed to work might point the way to better standards: “By figuring out how the trait normally functions or normally evolved to function, you have a conceptual blueprint about how the trait works, and it’s from that that you can see where things have broken down.”

“We’re nowhere near any of that in psychiatry,” he said, but it’s where he’d like to be.

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WILL THINKING OF DEPRESSION as an adaptive trait end up changing how we treat it? Steven Hollon, a professor of psychology at Vanderbilt University, thinks it’s an interesting possibility. “Most things that don’t serve a useful purpose tend to drop out along the line, and depression hasn’t,” he told Op-Talk. “You have to wonder if it plays some kind of role.”

Dr. Andrews’s idea of rumination as an aid to problem-solving is “certainly not widely accepted yet,” Dr. Hollon added, “but that doesn’t mean he won’t turn out to be right. And to develop a measure to get at the constructs he has in mind is an absolutely essential step along the way.”

Andrew H. Miller, a professor of psychiatry and behavioral sciences who has studied the relationship between depression and inflammation, is somewhat more skeptical. The idea that the disorder can help with problem-solving is “one of the more popular psychological theories of the purpose of depression,” he told Op-Talk. But “getting depressed to kind of think through your problems seems to be a pretty high-cost” adaptation, he said, “because depression’s no day at the beach.”

Clinicians who treat depressed people, he added, often find that “they’re ruminative in a way that really is very self-defeating and self-destructive.”

“I am wholly supportive of the notion that depression in part is adaptive,” he said. But he believes it’s likely linked not necessarily to problem-solving but to the body’s inflammatory response, which helps it deal with illness or injury: “We feel that the behavioral response that accompanies depression is really part and parcel of the entire physiology of responding to infectious agents or wounding, that inflammation and the behavioral changes that are associated with it go together.”

This doesn’t mean he thinks depression is always caused by infection: “There’s never been enough compelling data to isolate one or even several infectious agents that are reliably associated with the development of depression.” Rather, he thinks an infection may be one source of inflammation, which in turn can lead to depression. Other possible sources of inflammation, he said, include obesity, chronic stress or abuse or neglect in early childhood.

A significant body of research, he said, supports “inflammation as being sort of a common denominator, and then there are a number of ways to get there. And I think infectious agents are one path of many roads to Rome.”

His team has experimented with treating depressed patients with an anti-inflammatory drug, and found that those with high levels of a particular blood marker for inflammation improved significantly. “This for us in psychiatry is a first,” he said, “where you can actually measure something in the blood.” Such an approach “gets into personalized medicine in a way that is very exciting for us in psychiatry.”

However, he cautioned, “nobody’s figured out what’s the best anti-inflammatory.” And most researchers “are still at the point of the proof of concept, making sure that if you do in fact block inflammation that that would reduce these behavioral changes.”

Dr. Miller also noted that only about 20 to 30 percent of depressed patients show high levels of inflammation. These patients are also less likely than others to respond well to current forms of treatment for depression.

Indeed, what many researchers seem to agree on is that depression may not be one illness at all. It’s “probably the case that it’s not a single disorder,” said Dr. Hollon. “It’s probably the fever of modern psychiatry — a lot of different things can cause it.”

And while they’ve made progress, researchers are still trying to find out what all those things are.