Imagine Mike. For the past year Mike has become increasingly less interested in playing soccer (his favorite sport) and finds it difficult to get out of bed every morning. He feels tired all day since he has trouble sleeping and has difficulty concentrating at work. When his job becomes very stressful, he feels that life may be better if he was not around. According to the DSM-5, Mike is diagnosed with Major Depressive Disorder (MDD). This disorder has a lifetime prevalence of 17-21% worldwide, but only 30-40% of patients respond to the standard first line treatment of antidepressants (Rocha et. al., 2016). This means that a majority of clients diagnosed with MDD will not have a successful and stabilized response to the first choice of treatment. In order to improve the success of first line therapy and decrease side effects, researchers are currently on the hunt for the biological basis of depression. One protein found in the brain that proves some promise is the relationship between brain derived neutrophic factor (BDNF) and depression. This growth factor is the first of its kind to link the effectiveness of a variety of treatments such as antidepressants, stimulation, and exercise to the normalizing levels of BDNF. If there was a direct way to target BDNF with minimal side effects, an effective treatment for depression may be discovered (Higgins & George, 2013).
BDNF is a growth factor plays a role neurogenesis, or the creation and differentiation of neurons. More specifically, BNDF creates a link between a given treatment and the depressive symptoms. Biologically, depression has shown to prevent the expression of BDNF, which inhibits the proliferation and differentiation of neurons in the brain (Higgins & George, 2013). A reduction in BDNF also shows links to immobility, which may explain the psychomotor delay found in some patients diagnosed with major depressive disorder (Galvez-Contreras et. al., 2016). Current research is focusing on the role and regulation of BDNF levels in the brain to treat depression. For example, studies have shown that a single infusion of BDNF into the ventricles of the brain, or directly into the hippocampus, is enough to induce a rapid and sustained anti-depressant-like effect (Bjorkholm and Monteggia, 2016). This study suggests that normalizing BDNF levels in the brain plays a direct role in treating depression. While researchers know that BDNF plays some role in treating depression, the current focus is to determine the exact mechanism BDNF plays in depression, and how new treatments can focus on re-establishing these levels with minimal side effects.
One treatment that has shown significant improvements in treatment refractory depression is the use of electroconvulsive therapy (ECT), or the induction of seizure activity through a controlled passage of electrical current in the brain. ECT is typically reserved for severe depression, and is most effective for patients who do not respond to antidepressants or other front line options (Rocha et. al., 2016). In a meta-analysis (2016), it was concluded that ECT treatment increases BDNF and is one of the most potent and rapid enhancers of the hippocampus. This is significant since the hippocampus is one part of the brain that has been found to decrease in volume with major depressive disorder. In order to predict the level of response in ECT, further studies were conducted to determine the link between BDNF and the rate of cognitive improvement. While baseline cognitive performance did not play a role in successful ECT treatment response, the rate at which cognitive performance increased predicted a successful response (Mikoteit et. al., 2015). Currently, the success of ECT relies on the rate at which cognitive improvement occurs and the severity of the depression. While this is a step in the right direction, much more research needs to be conducted to prove the effectiveness of ECT with accuracy.
Non-pharmacological treatment that targets the regulation of BDNF provides an alternative to the standard anti-depressant medications. With side effects such as increased falls and weight gain, anti-depressant medications are not specifically targeting the origin of one’s depression. Exercise, a non-pharmacological alternative, has been proven to normalize BDNF levels in the brain and has even shown a greater protection against relapse compared to medications (Dotson et. al., 2016). More specifically, prescribed exercise (with a specific goal in mind) has shown to increase BDNF (Meyer et. al., 2016). The study suggests that being directed to exercise at a given intensity was more effective than having a participant exercise at his/her preferred intensity. Providing clear and measureable expectations for exercise may lead to better depressive symptom management since the individual has an opportunity to feel successful. Therefore, preferred and self-directed exercise intensity limits the participant’s perception of success compared to the success from an exercise regimen set by a health care provider.
The initial connection between BDNF and depression can lead to a host of different treatments that can be more effective than the current treatments. Not only does more research need to be conducted to determine the biological basis of depression, subsequent research needs to be conduced to determine specific treatments for depression that target BDNF levels. As new research occurs, BDNF will continue to play a critical role in new treatments for depression with fewer side effects. Therefore, Mike may have a treatment in the near future that targets his specific depression with minimal side effects.
American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.).
Björkholm, C., & Monteggia, L. M. (2016). BDNF – a key transducer of antidepressant effects. Neuropharmacology, 102, 72-79. doi:10.1016/j.neuropharm.2015.10.034
Dotson, V. M., Hsu, F., Langaee, T. Y., McDonough, C. W., King, A. C., Cohen, R. A., . . . Pahor, M. (2016). Genetic Moderators of the Impact of Physical Activity on Depressive Symptoms. J Frailty Aging, 5(1), 6-14. doi:10.14283/jfa.2016.76
Galvez-Contreras, A. Y., Campos-Ordonez, T., Lopez-Virgen, V., Gomez-Plascencia, J., Ramos-Zuniga, R., & Gonzalez-Perez, O. (2016). Growth factors as clinical biomarkers of prognosis and diagnosis in psychiatric disorders. Cytokine & Growth Factor Reviews. doi:10.1016/j.cytogfr.2016.08.004
Higgins, E. & George, M. (2013). The neuroscience of clinical psychiatry. Philadelphia, PA: Lippincott Williams & Wilkins.
Meyer, J. D., Ellingson, L. D., Koltyn, K. F., Stegner, A. J., Kim, J., & Cook, D. B. (2016). Psychobiological Responses to Preferred and Prescribed Intensity Exercise in Major Depressive Disorder. Medicine & Science in Sports & Exercise, 48(11), 2207-2215. doi:10.1249/mss.0000000000001022
Mikoteit, T., Hemmeter, U., Eckert, A., Brand, S., Bischof, R., Delini-Stula, A., . . . Beck, J. (2015). Improved Alertness Is Associated with Early Increase in Serum Brain-Derived Neurotrophic Factor and Antidepressant Treatment Outcome in Major Depression. Neuropsychobiology, 72(1), 16-28. doi:10.1159/000437439
Rocha, R. B., Dondossola, E. R., Grande, A. J., Colonetti, T., Ceretta, L. B., Passos, I. C., . . . Rosa, M. I. (2016). Increased BDNF levels after electroconvulsive therapy in patients with major depressive disorder: A meta-analysis study. Journal of Psychiatric Research, 83, 47-53. doi:10.1016/j.jpsychires.2016.08.004