Major depression clears up with personalized brain stimulation

An endless torment were the years when 36-year-old Sarah struggled every day to resist her darkest thoughts, hour after hour. Antidepressants, behavioral therapy, electroshock—she had tried every possible treatment, nothing helped the severe depression that had plagued her since childhood. But in June 2020, American neurosurgeon Edward Chang placed a flat device in her skull and two electrodes in her brain. That device not only stimulates her brain specifically at the spot that relieves her depression, but also detects when that electrical stimulation is needed. Her depression is now a distant nightmare, she says during a press conference of Nature Medicine. She is the very first test subject in the research that appeared on Monday in that scientific journal.

Deep brain stimulation is a promising treatment for severe epilepsy and Parkinson’s disease, among others. An electrode in the affected area of ​​the brain, coupled with a device implanted under the collarbone that continuously delivers current pulses, often offers a dramatic improvement in symptoms.

Compulsive disorders

Deep brain stimulation is also used for psychiatric disorders such as severe depression and anxiety and compulsive disorders when all other treatment options do not work. But the results in severe depression are mixed. “That’s because different brain circuits cause the different symptoms of depression in each patient,” says psychiatrist Katherine Scangos of the University of California at San Francisco. Together with Chang, she therefore looked for a way to tailor the treatment personally.

Scangos and Chang first mapped out which brain circuits played a role in Sarah’s depression. They stuck ten thin electrodes on either side of her brain in five brain regions known to be involved in emotional living. They took turns stimulating them and recording the effect on the depressive symptoms for ten days. The stimulation of an area called the ventral striatum consistently cleared the symptoms in Sarah (who only wants to be publicized by her first name for privacy reasons).

Immediately after the electrical stimulation for a first test, she started laughing out loud, she says. No fake smile, but a genuine, sincere smile for the first time in five years.

The researchers also discovered that this brain area was connected to another area, the amygdala, which plays a role in anxiety, among other things. A certain brain activity there predicted when Sarah’s feelings of depression were most intense.

Severe Epilepsy

A sensor in her right amygdala now continuously registers in Sarah whether the brain activity there is becoming abnormal. When that happens, the device in her skull bone — no bigger than 3 by 6 cm — delivers electrical pulses into the ventral striatum. The system uses much less power than classic deep brain stimulation with sustained pulses. The battery can last at least ten years with the settings that Sarah has. Thanks to the subtle adjustment, she does not suffer from side effects. The device with the sensor and electrode, the RNS System from manufacturer NeuroPace, is approved in the United States for the treatment of severe epilepsy. The Americans converted it for their experimental treatment for use in depression – it is not yet on the market for that.

With the permanent implant in it, Sarah was able to rebuild a life worth living step by step. Within a few weeks, her suicidal thoughts disappeared. “After that, my view of the world slowly changed. Depression ruled my whole life, I had to relearn everything: what I like to do, and to have my own opinion. I could finally apply things that I had learned in therapy.”

Stigma

The results are pricey. The research teaches the Americans a lot about which circuits are involved in depression, and how the different brain regions are related and work together. Much research is still needed to learn what is critical to treatment and what is not, what the depression circuitry looks like in other patients, and whether this could become a treatment for a wider group of patients. For example, it is not yet clear whether the brain activity changes over time as a result of the stimulation – perhaps the brain adapts and stimulation is no longer necessary over time. Chang and his colleagues have now equipped two other patients with the system, and are looking to add nine more.

Sarah feels empowered by the whole experiment. All her life, people around her have been saying that she has to get herself together, and that it will pass. Or they offer tips or treatments. Well-intentioned, but that stigma of depression is by far the hardest part. “I’ve done everything, and none of it worked. It actually exacerbated my depression and feeling of inferiority. You feel like the worst patient in the world.” This treatment makes it clear that her major depression is a brain disorder that won’t go away if you try hard enough. “No one says to someone with Parkinson’s disease, ‘Come on, put your shoulders down, it’ll be over’.”

stunned

Her environment noticed that the stimulation was working before she herself. Whoever drove her home when the device was first turned on was stunned at what Sarah said when she saw the San Francisco Bay and the swamps surrounding it. “How beautiful, all those different colors, and what a beautiful light.”

You can talk about suicide at the national helpline 113 Suicide Prevention. Phone 0800-0113 or www.113.nl

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