By Alice Barocco
Major depressive disorder (MDD), more commonly known as clinical depression, currently impacts the lives of more than 264 million people worldwide. Affecting adolescents as young as 12 years old to adults 50 and older, clinical depression is the leading cause of disability in the world (WHO, 2020). From the Latin word deprimere, literally meaning to ‘press down’ (Kanter et al., 2008), the term itself already alludes to patients having to deal with feelings of heaviness and chronic sadness. Clinical depression is mainly characterized by continuous low mood, a lack of motivation or interest, and feelings of hopelessness and helplessness (NHS, 2019). Dr. Cindy L Carmack, licensed clinical psychologist and Associate Professor at The University of Texas MD Anderson Cancer Center, simplifies the concept for us and describes depression as being when patients ‘lose interest in things that used to make them happy’ (Carmack, 2019).
However, when assessing the roots and causes of depression, the situation is far from being black-and-white. Despite decades of research, the neuroscience underpinning depression is poorly characterized even at the basest levels, with answers to fundamental questions such as ‘Where in the brain is depression?’ remaining elusive. This is mainly due to the heterogenous presentation of MDD across patients, as well as the difficulties in examining and imaging the fascinatingly complex human brain (Pandya et al., 2019). Recently, worldwide concentrated research efforts have implemented numerous experimental approaches – ranging from functional imaging to brain stimulation – to be able to more accurately localize depression in the brain (Koenigs & Grafman, 2009). The goal was to use this newly acquired knowledge to develop more effective treatment options associated with fewer side effects than antidepressants, especially for patients with obstinate depression (i.e. treatment-resistant depression (TRD)) (Rizvi & Khan, 2019). Following such research, the dorsolateral prefrontal cortex (DLPFC), part of the brain’s frontal lobes (Sturm, Haase & Levenson 2016), has been identified as being dysregulated in MDD patients (Rizvi & Khan, 2019). Functional imaging studies provide evidence of DLPFC, usually responsible for cognitive functions such as intention formation, also being recruited during emotional regulation (Koenigs & Grafman, 2009). Additionally, research conducted by Grimm et al. (2008) reported MDD patients showing DLPFC hypoactivity during emotional judgment when asked to categorize images presented to them as being positive or negative in content. These lower levels of excitability in the left DLPFC are speculated to be a potential cause of depression and, as a result, novel therapies have been developed which specifically target this brain region.
One of the most recent ones, which obtained outstanding positive results, is transcranial magnetic stimulation (TMS) (Rizvi & Khan, 2019). TMS was firstly introduced in 1985 by Anthony Baker at the University of Sheffield in England (Basil et al., 2005), but was only recently approved by the National Institute for Health and Care Excellence (NICE) as a valid treatment for MDD in 2015 (NICE, 2015). The Indian Journal of Psychological Medicine describes TMS as ‘state of the art’ therapy and reports a 50-55% response rate to this treatment, followed by a 30-35% remission rate, in MDD patients (Reddy & Vijay, 2017).
TMS involves stimulation of the left DLPFC noninvasively (Rizvi & Khan, 2019) and has been most commonly associated only with mild side effects such as headaches and light-headedness (Mayo Clinical Staff, 2018). The treatment is based on two basic physics principles: Ampere’s law and Faraday’s principle of electromagnetic induction (Basil et al., 2005). Using high-frequency electromagnetic induction, TMS is able to trigger the depolarization of hypoactive DLPFC cortical neurons in MDD patients (Rizvi & Khan, 2019). More specifically, the therapy consists of a TMS machine inducing a short pulse of electric current in a coil, provoking a quick changing magnetic field in the coil (Ampere’s law). This changing magnetic field induces the formation of eddy currents across neural pathways (Faraday’s principle) (Huang, 2018). In simpler terms, TMS induces an electric current isolated to a target area of the brain, using repetitive pulsating magnetic fields generated by an electromagnet placed on a specific region of the scalp of the patient (Pandya et al., 2019). What is most fascinating about TMS is its ability to target, stimulate and strengthen neural pathways involved in the regulation of mood and emotions, training them, just like a muscle, to start firing again independently at the correct frequency without electrodes (Rizvi & Khan, 2019). Thus, this procedure is completely pain-free and does not require any kind of sedation with anaesthesia (Mayo Clinical Staff, 2018). The strength with which the target neural pathways are stimulated by the electromagnetic coil can be regulated, ranging from low levels of neuronal excitability at 1 Hz to high levels at 10-20 Hz. Despite the many perks of TMS, it is important to mention the type of patient compliance that such a therapy demands: patients are required to undertake a total of 20-30 treatment sessions, undergoing an average of five 60 minutes daily sessions over the course of three to six weeks (Rizvi & Khan, 2019). Clearly TMS demands a great commitment from MDD patients, however, its highly promising results should not be forgotten when deciding whether to undertake this therapy.
After decades of research yielding evidence in favour of TMS as a therapy for MDD, clinical efficacy of this pioneering technique as an antidepressant has finally been well established (Rizvi & Khan, 2019). Most importantly, such a novel technique represents not only hope, but a more concrete medical plan for patients that suffer from TRD, who had previously been unable to benefit from the help of antidepressants.
References:
Basil, B., Mahmud, J., Mathews, M., Rodriguez, C., & Adetunji, B. (2005). Is There Evidence for Effectiveness of Transcranial Magnetic Stimulation in the Treatment of Psychiatric Disorders?. Psychiatry (Edgmont). 2 (11), 64–69. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2993526/ [Accessed: 27 June 2021].
Grimm, S., Beck, J., Schuepbach, D., Hell, D., Boesiger, P., Bermpohl, F., Niehaus, L., Boeker, H. & Northoff, G. (2008) Imbalance between Left and Right Dorsolateral Prefrontal Cortex in Major Depression Is Linked to Negative Emotional Judgment: An fMRI Study in Severe Major Depressive Disorder. Biological Psychiatry. 63 (4), 369-376. Available from: doi: 10.1016/j.biopsych.2007.05.033
Huang, Y. (2018) SP-2. What dose TMS stimulate?. Clinical Neurophysiology. 129 (5), e17. Available from: doi: 10.1016/j.clinph.2018.02.008
Kanter, J., Busch, A., Weeks, C. and Landes, S. (2008) The nature of clinical depression: Symptoms, syndromes, and behavior analysis. The Behavior Analyst. 31 (1), 1-21. Available from: doi: 10.1007/BF03392158
Koenigs, M., & Grafman, J. (2009) The functional neuroanatomy of depression: Distinct roles for ventromedial and dorsolateral prefrontal cortex. Behavioural Brain Research. 201 (2), 239–243. Available from: doi: 10.1016/j.bbr.2009.03.004
Lustgarten Foundation Pancreatic Cancer Research. (2019) Interview with an Expert: Understanding Depression and Anxiety. Available from: https://lustgarten.org/interview-with-an-expert-understanding-depression-and-anxiety/ [Accessed: 26 June 2021].
Mayo Clinical Staff. (2018) Transcranial magnetic stimulation. Available from:
https://www.mayoclinic.org/tests-procedures/transcranial-magnetic-stimulation/about/pac-20384625 [Accessed: 27 June 2021].
National Institute for Health and Care Excellence. (2015) Repetitive transcranial magnetic stimulation for depression. Available from: https://www.nice.org.uk/guidance/ipg542 [Accessed: 27 June 2021].
NHS. (2019) Symptoms – Clinical depression. Available from: https://www.nhs.uk/mental-health/conditions/clinical-depression/symptoms/ [Accessed: 26 June 2021].
Pandya, M., Altinay, M., Malone, D. A., Jr, & Anand, A. (2012) Where in the Brain Is Depression?. Current Psychiatry Reports. 14 (6), 634–642. Available from: doi: 10.1007/s11920-012-0322-7
Reddy MS & Vijay MS. (2017) Repetitive Transcranial Magnetic Stimulation for Depression: State of the Art. Indian Journal of Psychological Medicine. 39 (1), 1-3. Available from: doi: 10.4103/0253-7176.198951
Rizvi, S., & Khan, A. M. (2019) Use of Transcranial Magnetic Stimulation for Depression. Cureus. 11 (5), e4736. Available from: doi: 10.7759/cureus.4736
World Health Organisation. (2020) Depression. Available from: https://www.who.int/news-room/fact-sheets/detail/depression [Accessed: 26 June 2021].
Sturm, V. E., Haase, C. M & Levenson, R. W. (2016) Emotional Dysfunction in Psychopathology and Neuropathology: Neural and Genetic Pathways. In: Lehner, T., Miller B. L. & State, M. W. (eds.) Genomics, Circuits, and Pathways in Clinical Neuropsychiatry. Academic Press, pp. 345-364. Available from: https://www.sciencedirect.com/topics/psychology/dorsolateral-prefrontal-cortex [Accessed: 26 June 2021].
Imperial Bioscience Review 