Marris Szeliga, a patient and employee of psychiatrist Hasan Asif, is fitted with an EEG cap that will allow him to analyze her brain-wave activity. (Yana Paskova For The Washington Post)

Nearly every day, researchers report findings about genetic or cellular associations with mental illness. But despite years of searching, no one has identified a single biological cause for any mental illness, proved that a chemical imbalance in the brain is at the root of any mental disorder, or positively shown that any medication corrects such a chemical imbalance.

“There’s been an intense search for biomarkers for the last 40 years, and so far we’ve come up empty,” said psychiatrist Allen Frances, a professor emeritus at the Duke University School of Medicine. “It’s been oversold. The decade of the brain came up empty. It should teach us to be humbler.”

The leading drugs for depression — the selective serotonin reuptake inhibitors, or SSRIs — are designed to ease symptoms by boosting serotonin, one of the brain’s pleasure chemicals. But it’s not known whether that corrects an imbalance, because there’s no way to directly measure a person’s neurochemical levels. Experts also can’t explain why antidepressants work only 40 percent of the time or why, when they do, it takes weeks for most patients to feel the effects since the levels are boosted almost immediately.

The chief complaint about today’s psychiatric medications is the same one cited by those frustrated by the lack of progress on Alzheimer’s: They don’t treat the disease, just the symptoms, and they don’t even do that very well.

Rather than targeting brain chemistry to reduce symptoms, people such as Insel want to focus on brain circuitry. Their efforts have been bolstered by advances in technology and imaging that now allow scientists not only to see deeper into the brain, but also to study single brain cells to determine which circuits and neurons underlie specific mental and emotional states. Many of these advances come from fields as disparate as physics and electrical engineering — as well as the new field of optogenetics, which uses light to manipulate neurons.

In the past, brain imaging allowed scientists to identify which groups of neurons were active when, say, a lab mouse was aggressive, but not whether the neurons were causing the aggressive behavior. Then a few years ago, researchers at the California Institute of Technology injected into the hypothalamus of a mouse a modified gene that made certain cells sensitive to light.

They then inserted a hair-thin fiber-optic thread into the mouse’s skull and delivered bursts of light into those cells to activate them. The mouse became aggressive. When the researchers turned the light off, the activity in those specific hypothalamic cells ceased, and the mouse returned to a calm, normal state.

Because the technique is too invasive for people, researchers are now looking at nanotechnology and even magnets as a way to switch cells on and off in humans. Connecting specific symptoms with specific groups of neurons, and then manipulating those cells, would represent a watershed moment.