By Alise Gentile
Deep Brain Stimulation
Deep Brain Stimulation (DBS) is an invasive neural treatment that utilizes electrodes to facilitate electrical currents to certain cerebral regions. These electrodes are connected to a device placed inside of the chest, called an implantable pulse generator, or IPG, which controls the frequency and intensity of the electrical currents used to stimulate brain cells within the regions of the brain. This low-risk treatment is widely used to manage conditions involving involuntary movements, such as Parkinson’s disease and Tourette syndrome. Conditions such as schizophrenia and depression show great improvement from DBS, although it is important to note that further research is required to completely validate this.
The image above depicts the placement of DBS devices.
Treatment Resistant Depression
Treatment Resistant Depression (TRD) is a branch of Major Depressive Disorder (MDD) in which symptoms do not improve with two or more antidepressant medications. In accordance with the Anxiety and Depression Association of America, MDD eventually affects 21% of adults in the US with MDD being the top disability for
Americans aged 15-44. Of this percentage, 30%
of all MDD patients have been diagnosed with TRD. Recent studies contain implications that TRD may be caused by dysfunctions within the mesolimbic dopamine system, formed by the nucleus accumbens (NAc) and ventral tegmental area (VTA), which could account for the lack of motivation within individuals diagnosed with TRD. Aside from neural chemistry, TRD can also be attributed to chronic stress and genetics.
DBS as Treatment for TRD
One of the major indicators for diagnosing TRD is anhedonia - the absence of pleasure and satisfaction. Physiologically speaking, anhedonia traits can be traced to multiple reward pathway regions, such as the NAc, VTA, or inferior thalamic peduncle. Although, researchers have also experimented with various other regions involved with reward systems, such as the medial forebrain bundle.
The VTA sends dopamine transmitters to the ventral capsule (VC) that operates as an essential node for the brain’s reward system, which places an emphasis on this region. In an effort to revive mood flexibility and improve motivational levels, DBS is used to activate stagnant neurons in the brain’s reward circuit.
The VTA region, a major part of the brain’s reward system. Image by socialsci.libretexts.org.
Studies and Clinical Trials
Currently, DBS is only used as an experimental form of treatment in professional research clinics. Beijing researchers Nan Song, Zhenhong Liu, Yan Gao, Shanshan Lu, Shenglian Yang, and Chao Yuan collaborated to perform DBS on mouse models in an experiment concerning the effects of Nac-DBS. Using the CUMS ethical model of induced depression on rodents, the researchers placed the mice in different scenarios inducing depressive symptoms, such as covering the mice’s cage floor with water and placing the mice in a cage containing a repulsive odor. The rodents underwent DBS to the NAc and were placed into “stimulation chambers” for an hour per day. The results showed that NAc stimulation greatly increased dopamine in the VTA, correcting the rodent’s depressive symptoms.
In a randomized clinical trial conducted by Isidoor O. Bergfield, Mariska Mantione, Mechteld L. C. Hoogendorn, and more, twenty-five TRD patients underwent DBS in a randomized, double-blind experiment. The patients received DBS via an implantation of four electrodes to the middle of the NAc with steady frequencies on a two six-week block phase (DBS stimulator on and DBS stimulator off). Using the 17-item Hamilton Depression Rating Scale, the researchers concluded that patients illustrated significant improvement succeeding DBS, with scores lowering from 20.3-24.1 (at a 95% confidence interval) with an average score of 22.2, to 12.3-19.5 (at a 95% confidence interval) with an average of 15.9.
Limitations
Solely utilized in experimental trials, DBS can have some limitations. Depending on the region of the brain in which DBS was administered, it is possible that depressive symptoms may return. According to the second clinical trial mentioned above, the removal of DBS in the VC region caused symptoms to return within a week. In addition, symptoms of TRD vary patient-to-patient, which can complicate treatments depending on the area that electrodes are placed. As the authors of “Deep Brain Stimulation for Depression” (Neurotherapeutics, Volume 19, Issue 4) stated, “ it is likely that patients within a specific subgroup of symptoms will respond preferentially to different targets.” Another general limitation of any emerging neural treatments is the possibility of the placebo effect, where the patient's brain may imagine progressing conditions even though the treatment may not necessarily be working.
HAM-D-17 for DBS, image provided by treat-major-depression.com
Conclusion
DBS is a surgical procedure involving the implantation of electrodes into various brain regions. While most commonly used for treatment of dystonia, emerging research has provided overwhelming evidence of DBS as a valid treatment for depression that demonstrates resistance to common medication. DBS is extremely likely to stimulate and increase dopamine neurons in the VTA in humans and decrease depressive symptoms. However, prospective inquiries into the subject are necessary in order to validate DBS as an official medical treatment.
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