To Treat Depression, a New Approach Tries Training the Brain

A still image from an attention bias modification treatment. The woman has a neutral expression at left but a sad one at right. Patients’ attention is trained toward the neutral face.
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Should depression be treated more like a stroke?

That’s the view of a growing number of researchers developing new psychological treatments that aim to directly target the particular brain dysfunctions and cognitive and emotional processes understood to underlie depression.

The approach is to think of a brain region that goes awry as “more like a muscle that is atrophied,” says Greg J. Siegle, director of the Program in Cognitive Affective Neuroscience at the University of Pittsburgh School of Medicine. “The solution to an atrophied muscle is to rehab it.”

Many of the new treatments involve simple computer games. One technique uses math problems and audio of chirping birds to activate a part of the brain involved in emotion regulation. Another uses pairs of words and faces to train depressed people to disengage from negative emotional stimuli. Other approaches combine computer games with actual electrical stimulation of brain regions.


Research on the new treatments is still in early stages. So far, studies have been small, the results mixed. Scientists are still tinkering with approaches and appropriate doses. The therapies also likely won’t work for everyone. Researchers have found that not every depressed brain looks alike. So treatments that target specific dysfunctions may only be effective for a particular slice of patients. Many scientists believe they will be used to enhance the efficacy of current therapies.

There is a big need for new treatment. Almost 17% of Americans will suffer from major depression during their lifetime, according to a 2012 study published in the International Journal of Methods in Psychiatric Research. Not everyone responds to the current leading therapies, which include antidepressant medications, and psychological approaches such as cognitive behavioral therapy and interpersonal psychotherapy.

In a study published in the American Journal of Psychiatry in 2006 of nearly 3,000 patients taking the popular antidepressant citalopram (brand name Celexa) for up to 14 weeks, only about one-third achieved remission from their depression. (About half of the participants responded to the drug, meaning that their scores on a survey assessing depression symptoms improved by at least 50% during the trial.) Patients often need to try several medications to get relief from their symptoms or need to switch because of bothersome side effects.

With cognitive behavioral therapy, patients are coached to reappraise their negative thoughts—“Nobody loves me,” for example—and examine the evidence to shift the thoughts to something more realistic. The treatment also often includes behavioral activation, scheduling activities that used to be pleasurable for the patient or can give a sense of accomplishment. For someone in a deep depression, it can start with something as simple as getting out of bed or taking a shower.

Dr. Greg Siegle at the University of Pittsburgh Medical Center has developed a new treatment for depression that targets the underlying brain dysfunction that many depressed people show.
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But cognitive behavioral therapy “is hard work,” says Simon Rego, director of psychology training at Montefiore Medical Center in the Bronx, N.Y. “When you’re depressed, you don’t have high motivation or energy or concentration, yet [the therapy] is asking you to do all those things.”

One of the new alternative treatments being tested is cognitive control training, or CCT, which consists of two 15-minute exercises.

In the first, patients are told to add a series of numbers following a specific set of rules. This task has been shown to activate the dorsal lateral prefrontal cortex, a part of the brain that is involved in both emotion regulation and executive control, or “voluntarily thinking about what you want to when you want to,” says Dr. Siegle, who developed CCT. This section of the brain tends to be underactive in depressed people and may contribute to rumination, that endless loop of negative thinking that often plagues them.

Another part of CCT has patients listening to audio of birds chirping. The aim is to help people direct their attention to these external sounds instead of their own thoughts.

In a 2014 study published in Behavioural and Cognitive Psychotherapy involving 48 people with depressed mood, those receiving three sessions of CCT over a two-week period saw their depression scores drop more than those receiving a control exercise that trained peripheral vision.

At least one research group in Australia is combining CCT with transcranial direct current stimulation of the dorsal lateral prefrontal cortex, where a gentle electric current is directed into the brain via electrodes placed on the scalp. In a study published in Brain Stimulation in 2014, depressed patients who underwent this combination of therapies had on average a 46.5% reduction in depression symptoms three weeks after treatment. Those who just had CCT had a 17.2% reduction and those who had just the electrical therapy had just an 8.9% reduction.

Dr. Siegle has created a new exercise for people who have a tough time paying attention. In it, two electrodes are placed on the arm and a weak electric current is run between them. “It creates an annoying itch under the skin,” Dr. Siegle says. “You could imagine you couldn’t easily ruminate when that was going on,” he says.

Sean Elliott tried antidepressants and therapy before turning to a combination of cognitive control training and transcranial direct current stimulation, which he said has helped his depression.
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Sean Elliott, a 37-year-old science educator from Melbourne, Australia, had tried antidepressant medication and therapy for his depression, but found that neither helped much. He also didn’t like the dizziness he felt when he missed a dose of his medication. So he tried CCT and tDCS through a study by the Australian research group earlier this year.

Months after the new treatment, he says he’s better able to bounce back from arguments. He no longer has what he calls wipeout days where he can’t get out of bed or leave the house: “I can’t say it has been a light switch, but it is a gradual improvement.”

Interpretation Bias Modification or Cognitive Bias Modification-Interpretation (CBM-I) is another new treatment that aims to counteract the tendency of depressed people to interpret ambiguous situations in a negative way.

In one version of the treatment, patients are presented with a series of written scenarios, the majority of which are resolved positively. The last word includes a missing letter and patients are instructed to fill it in.

The goal is to “get that bias more toward neutral and positive. The thought is, if you’re able to do that, it may lead to beneficial effects for mood,” says Jamie A. Micco, assistant professor of psychology at Harvard Medical School.

Many depressed people have difficulty disengaging their attention from negative emotional stimuli. Another relatively new treatment being studied, attention bias modification, aims to counteract that. Patients are shown two faces side by side, one with a neutral expression, the other with a sad expression. Patients’ attention is trained away from the sad face. The treatment can also juxtapose neutral and negative words—“song” versus “idiot,” for example.

In a study published in 2015 in the Journal of Abnormal Psychology, ABM reduced negative attention bias in patients with depression. But it and a placebo treatment both reduced depression symptoms by an average of 40% for 52 subjects over four weeks. The authors speculate that the placebo treatment may have enhanced attention, something that could have led to the symptom improvement.

About two-thirds of depressed people have this negative attention bias, says Christopher G. Beevers, a professor of psychology at the University of Texas in Austin and the lead author of the study. That means that one-third don’t. In the future, he hopes clinicians will be able to assess patients and direct them to treatments that address their particular neurobiological and cognitive dysfunctions.

“That is where a lot of this work is ultimately headed,” he says.

Write to Andrea Petersen at andrea.petersen@wsj.com


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