Treating Depression From the Inside Out

By: Mira Postelnek  |  May 13, 2022

By Mira Postelnek, Staff Writer

Although depression affects more than 264 million people and leads to thousands of annual deaths nationwide, little is known about this onerous mental illness. 

Scientists believe that depression is influenced by many factors, including chemical imbalances in the brain, personality changes, environmental factors, and a person’s genetics. There are multiple treatment options, such as medication or therapy, but for patients with no other treatment option that worked, they can try a treatment known as electroconvulsive therapy (ECT). ETC is utilized for severe depression cases and is an adaptive version of shock therapy. According to Mayo Clinic, while a person is under general anesthesia, electrical currents are sent through parts of the brain to trigger a seizure and alter brain chemistry. While this type of treatment may seem barbaric, it can have positive effects on the most severe depression cases. Unfortunately, there is a stigma surrounding ETC therapy that stems from the possible undesirable side effects that many patients experience. Furthermore, doctors question the benefit of ETC therapy since one in every ten ETC patients will experience little to no benefit from ETC. 

There is, however, a new treatment option on the horizon: brain implants to treat severe cases of depression. This treatment is modeled similarly to ETC in the sense that it utilizes a form of neuromodulation targeting that is tailored specifically to a patient’s symptoms. According to Katherine Scangos, M.D., Ph.D., an assistant professor in the Department of Psychiatry and Behavioral Sciences, “[t]he brain, like the heart, is an electrical organ, and there is a growing acceptance in the field that the faulty brain networks that cause depression – just like epilepsy or Parkinson’s disease – could be shifted into a healthier state by targeted stimulation.” Soon after remarking this, Dr. Scangos and colleagues mapped the effects of stimulation in the amygdala on mood-related brain sites in a patient with severe treatment-resistant depression. 

A paper published by Nature Medicine explains the research conducted by Scangos and her colleagues, which uses stimulation to treat resistant depression through a new device called NeuroPace RNS. This method, which was initially a treatment for epilepsy, is now being studied as a potential treatment for severe depression. NeuroPace RNS works by implanting the device in the right hemisphere of the patient’s brain and monitoring the patient’s amygdala for signs of depression. Then, doctors can supply electrical stimulation when they notice changes in the patient’s amygdala.

In early research done on NeuroPace RNS, researchers studied the patient’s brain through a minimally invasive approach called stereo-EEG before implanting the device. Researchers placed ten intracranial electrode leads into the brain of the patient, who then spent ten days engaged in “stimulus-response mapping,” which is essentially the researchers stimulating various parts of the brain and monitoring the effects on the patient. The researchers discovered that the patients felt joy and happiness when they activated the ventral striatum. This stimulation seemed to best address this particular patient’s primary symptoms of low energy and loss of pleasure in everyday activities. The patient stated she began to enjoy treatments because she hadn’t felt such a sense of joy in years. In the words of the patient, “[i]t struck me so clearly in that moment that my depression wasn’t something I was doing wrong or just needed to try harder to snap out of – it really was a problem in my brain that this stimulation was able to fix.” 

After making this discovery, the researchers had to determine the opportune time to activate this area in the brain. They continued their study by mapping the patient’s brain and found gamma oscillations in the amygdala. According to the research, the study found it was a reliable indicator of when the patient’s depression symptoms would spike. 

Based on this information, the patient had a wire placed in her amygdala that was coded to know when to administer the shock treatment. Stimulation was initiated in six-second bursts in the ventral striatum, increasing the patient’s feeling of happiness until the gamma oscillations decreased.  The treatment was then deemed effective, and the implant was dormant until the gamma oscillations triggered another wave of six-second bursts. The patient was provided with gentle stimulation throughout the day as necessary. According to the University of San Francisco study, the patient’s depressive symptoms virtually disappeared during the months of treatment with this implant. The patient reported that her symptoms, which she has struggled with for the past seven years, have almost completely vanished, despite significant stressors present in her current life. 

This was stage one utilizing NeuroPace RNS, and it was only performed on one patient. The following stages of research will have the patient spend six weeks off the device and then six weeks with the device turned on; this will evaluate whether the treatment is effective or a result of the placebo effect. There is a lot of research and tests to conduct before NeuroPace RNS can be utilized for broader use. However, NeuroPace RNS is an interesting new treatment that has the potential to help patients with debilitating depression who have been unable to find relief and are at high risk of suicide.

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