Part of the reason that scientists are still working in the “vague and imprecise realm,” as Monroe put it, is because they still don’t have a clear answer for what causes depression. In the 1960s, the dominant hypothesis was that it stemmed from a chemical imbalance in the brain, specifically from lower levels of the neurotransmitter serotonin. As a result, drug companies poured resources into developing “selective serotonin reuptake inhibitors” (SSRIs), drugs that increased the amount of serotonin in the brain. SSRIs (a group that includes Paxil, Zoloft, and Prozac, among others) are still the most commonly prescribed type of antidepressant—despite the fact that research has shown that lower levels of serotonin do not necessarily cause depression for all individuals. And in 2010, a review of three decades’ worth of studies on antidepressants found that while SSRIs can be helpful for severely depressed people, their effectiveness “may be minimal or nonexistent” in those with mild or moderate depression.
Bruce Cuthbert, the director of adult translational research and treatment development at the National Institute of Mental Health (NIMH), thinks that part of the problem is that researchers have largely focused their attention on finding a one-size-fits-all treatment that doesn’t exist. “When you do a clinical trial, you’re getting a bunch of people who are ‘depressed,’ but they’re actually very different,” he said. “It’s like comparing apples, pears, and tangerines. You’re not going to see a significant effect. You’re not going to be able to say, ‘This treatment works for fruits.’” Trying to create a singular treatment for depression, Cuthbert said, is like trying to create one for cancer: too unspecific to actually be helpful.
“While DSM has been described as a ‘Bible’ for the field, it is, at best, a dictionary, creating a set of labels and defining each,” the NIMH director Tom Insel wrote in 2013. “Unlike our definitions of ischemic heart disease, lymphoma, or AIDS, the DSM diagnoses are based on a consensus about clusters of clinical symptoms, not any objective laboratory measure.”
In 2010, Insel invited Cuthbert, who was then working as a psychology professor at the University of Minnesota, to help the NIMH develop a new framework for defining mental illness. The result, unveiled in 2013, was the Research Domain Criteria (RDoC), a system created to flip the way researchers think about mental disorders. Unlike the DSM, RDoC isn’t organized by disorder; instead, it’s organized around specific symptoms, like fear, anhedonia (the inability to feel pleasure), and willingness or unwillingness to work. The system also lists the genes, neural circuits, physical response, and self-reported behavior associated with each symptom.
The theory behind this RDoC system is that treating a specific symptom will produce better results than treating a broad category of illness. Many depression patients exhibit anhedonia, for example, but many others don’t. But if researchers took a group of patients who all displayed anhedonia, regardless of their diagnosis (it’s also a common symptom of schizophrenia) and tested treatments for that very specific symptom, they would get better results for treating anhedonia.