How can exercise have an antidepressant effect on the brain through BDNF?

Regular physical activity has long been known to have positive effects on mood and mental health. In this study, the antidepressant effect of exercise in the brain of patients with Major Depressive Disorder (MDD), which includes symptoms such as decreased mood and motivation caused by changes in the chemical molecules of the brain, was tested. Brain-Derived Neurotrophic Factor (BDNF) is a brain protein involved in neurogenesis that is often present in decreased levels in depressed individuals. The correlation between exercise and levels of BDNF and whether mood improves with higher amounts of BDNF was researched. Various studies show that physical activity may lead to an increase in BDNF in plasma or serum and an increase in hippocampal volume. It may also enhance synapse function and boost neuroplasticity, both of which are factors decreased in a depressed brain. These results show that through the BDNF mechanisms in the brain, exercise may have an antidepressant effect. Patients often report a better mood and more positive feelings after a consistent exercise regimen. This information can be utilized to create better treatment plans by monitoring BDNF and levels of similar proteins in patients with MDD.
MDD (Major Depressive Disorder), commonly known as depression, is one of the most common mental health disorders. It is characterized by an ever-present feeling of sadness or loss of interest that permeates all aspects of life. Other symptoms may include angry outbursts, anxiety, and reduced appetite. Around 17% of American adults will experience at least one depressive episode in their lifetime. There are a variety of potential causes for depression, including genetic predisposition, recent loss of a loved one, emotional conflicts, substance abuse, and serious illnesses. When someone begins suffering from depression, their primary care provider will supply a variety of treatment options. The current treatments for clinical depression range from antidepressant medications to therapy and improvements in diet and exercise [1]. Research in MDD patients has shown that people suffering from depression may have a smaller hippocampus (a memory region in the brain). There is also the neurogenesis theory that states that depression leads to decreased neurogenesis,the continuous regeneration of neurons and disposal of old nerve cells in the brain for maximum mental performance, [2] a decreased mood. Certain molecules that are especially involved in brain neurogenesis are typically found in abnormally low amounts in someone with a mental illness such as Major Depressive Disorder.
This article looks at Brain-Derived Neurotrophic Factor (BDNF), an important neurotrophin in the brain. Neurotrophins are a family of proteins that are often involved in the maintenance and growth of neurons in the brain. BDNF specifically focuses on neuroplasticity, which is how brain matter changes in relation to learning and memory [3]. Changes in BDNF levels have been seen in patients with Major Depressive Disorder, especially in areas such as the hippocampus. There are significant reductions in BDNF tested in plasma in people that are severely depressed [3]. Since exercise has long been known to have positive effects on mood and brain health in general, physical activity could change BDNF expression levels and have an impact on depression.
First, a literature search was conducted on exercise and its effects on the brain with regard to alleviating symptoms of depression. The NCBI databases and other peer-reviewed journals were explored to understand what compounds have an effect on the brain’s neurotransmitter processing mechanism and lead to a better mood. Out of the various molecules that play a role in the neurogenesis of the brain, BDNF was chosen as the focus of this article . Specifically, the effects of depression on BDNF and how exercise can reverse the impacts in MDD patients was explored. Studies were conducted on human patients with a control and experimental group and changes in mood and BDNF levels were measured over a period of time. The collected data of changes in BDNF expression revealed the potential of exercise as an antidepressant. The studies analyzed expression levels in brain samples versus changing mood in the patients to make these conclusions.
BDNF levels in depressed brains vs. normal brains after exercise
As mentioned in the background, it is known that BDNF levels are lower in the brains of depressed individuals. For example, one study was conducted on the elderly population in which BDNF serum levels were tested in two different groups of people after regular physical exercise for about a month. The baseline levels of both tested groups were as expected; the BDNF values in the depression group were about 200 pg/ml less than the normal, or control, group. However, after the exercise, there was a general increase of BDNF levels in both groups, meaning that brain function improves from physical activity. Notably, there was a higher percent increase in the serum of depressed patients than in that of the control patients [4]. Another meta-analysis study in which the researchers compiled the results of 11 studies comparing the BDNF serum values of depressed individuals to those of normal people demonstrated a significant decrease in BDNF levels if the person was experiencing depression. A similar meta-analysis was done on eight studies about the impacts of antidepressant treatment on BDNF levels and also revealed a significant BDNF increase with the addition of physical activity [5]. The p-values of both analysis experiments suggested high significance of results.
Exercise may cause increases in hippocampus volume
Along with the mentioned BDNF level increase, those who practice regular exercise may experience an increase in hippocampal volume. This is because the hippocampus usually becomes smaller and less active under the influence of a disorder such as MDD. The hippocampus is responsible for the growth of new neurons, plasticity, and centers of learning in the brain. Because BDNF operates through multiple signaling pathways, its gene expression is usually involved in the hippocampal area of the brain. Aerobic exercise allows for a greater blood flow, which may be another contributor to an increase in hippocampus size with physical activity. As portrayed by the results of the previously mentioned studies, serum levels are higher because of exercise, corresponding to higher activity of the hippocampus. This leads to better connectivity of neurons within the brain and higher function, both of which characterize recovery from depression. A study shows that chronic antidepressant treatment, such as daily physical activity for an extended period of time, may lead to plastic changes in the neurons and increased gene expressions of proteins such as BDNF [6]. Additionally, such treatment may aid the restructuring of chromatin (the material of which chromosomes are composed), which is involved with the transcription process, and induce regulators around the BDNF gene promoter to increase BDNF levels.

Greater BDNF levels have an antidepressant effect on mood
Increased serum levels in the brain caused by regular exercise have a positive effect on mood and lead some people to feel less depressed. For example, there was a research study done on 24 women who did regular physical activity, followed by testing of their BDNF levels and mood. The results indicated that with exercise, serum levels increased along with the baseline mood from the beginning of the study. BDNF, as a protein involved in neurogenesis and plasticity, serves as a mechanism to make the brain more active for patients who are depressed, therefore increasing mood [8]. Although a better mood is not necessarily the only factor needed for someone to get out of clinical depression, it is a major step in helping battle the disorder. As BDNF floods areas such as the hippocampus and prefrontal cortex after regular exercise, an antidepressant effect is initiated, similar to the mechanism of pills and other treatment options [9].

Overall, these results proved the original hypothesis that regular exercise has a positive effect on BDNF serum levels and may benefit the mood of patients facing depression. Interestingly, exercise may have a different effect on someone who is experiencing Major Depressive Disorder than someone who is not: some studies suggest that the percent increase of BDNF as a result of exercise is greater in depressed patients. As the hippocampus may be smaller in depressed individuals, a treatment such as exercise that increases the brain’s supply of molecules such as BDNF has a large positive effect on lessening symptoms. One of the reasons BDNF in particular is such a necessary protein in the mechanisms of antidepressant treatment is its function in the brain. As a neurotrophin, it is involved in the growth of new neurons in the brain, which controls all the productivity, performance, and emotional stability in a person. Hence, someone who is experiencing depression will have a harder time functioning at a high level because of their low protein levels, causing the commonly reported symptoms of MDD. The hippocampus is an important region of the brain that facilitates this kind of antidepressant treatment because it impacts most memory and cognitive functions and can expand with chronic physical activity.
Out of the many treatment options for depression, exercise is one of the most studied and impactful ones because it is a natural way to help alleviate negative effects and benefit mood. All of the studies and evidence shown above do indicate that doing regular physical activity may positively affect long-term serum values and mood; however, it is important to note that there must be a very specific type of exercise and time frame in order to have the intended effect. Most of the studies reviewed included aerobic exercise specifically, but further research is needed to ascertain whether other types of exercise such as weight training will have the same neurological effect. Furthermore, the main idea of exercise as a treatment for MDD is that it needs to be performed regularly for an extended period before any significant improvements can be seen. Based on the experiment studied, at least a month of continuous physical activity is needed for these benefits. Perhaps, a mix of exercise and other antidepressant treatments coupled together would be the most effective method to fight depression.
This study solidified the significance of processing proteins such as BDNF in the role of treating depression and increasing mood, suggesting potential protein-based treatment options to increase performance in the brain. In the future, other molecules and neurotrophins that are similar to BDNF can be studied to determine how exercise can affect their levels and role in MDD. Additionally, other factors such as diet or amount of sleep can also be tested for their effect on mood.
This study concluded that frequent exercise will increase BDNF levels in the brain and activate the hippocampus region, leading to improved mood in depressed patients. Various studies proved that the BDNF percent increase after exercise differs when comparing effects on subjects with and without depression, further highlighting BDNF’s complex role in brain function. Exercise may also cause a larger hippocampal region, which allows those who are depressed to experience heightened brain function and performance as well as improved mood. Thus, regular exercise can be considered an effective antidepressant because of neurotrophins like BDNF that facilitate physical activity’s influence on the brain and help to lessen depression symptoms. Suggestions for further research include studying the impacts of specific types of exercise or studying different molecules that may also lead to increased mood.

  1. “Depression (Major Depressive Disorder).” Mayo Clinic. Mayo Foundation for Medical Education and Research, February 3, 2018.
  2. Phillips, Cristy. “Brain-Derived Neurotrophic Factor, Depression, and Physical Activity: Making the Neuroplastic Connection.” Neural Plasticity 2017 (2017): 1–17.
  3. Gokce, Evrim, Emel Gunes, and Erhan Nalcaci. “Effect of Exercise on Cognition in Neurodegenerative Disorders: An Approach Focusing on BDNF.” Archives of Neuropsychiatry, 2019.
  4. Kurdi, Fauziah Nuraini, and Rostika Flora. “Physical Exercise Increased Brain-Derived Neurotrophic Factor in Elderly Population with Depression.” Open Access Macedonian Journal of Medical Sciences 7, no. 13 (2019): 2057–61.
  5. Sen, Srijan, Ronald Duman, and Gerard Sanacora. “Serum Brain-Derived Neurotrophic Factor, Depression, and Antidepressant Medications: Meta-Analyses and Implications.” Biological Psychiatry 64, no. 6 (2008): 527–32.
  6. Lee, Bun-Hee, and Yong-Ku Kim. “The Roles of BDNF in the Pathophysiology of Major Depression and in Antidepressant Treatment.” Psychiatry Investigation 7, no. 4 (2010): 231.
  7. Admin, and Name *. “Exercise-BDNF.” The 5 AM Mommy, October 19, 2020.
  8. Martinowich, Keri, and Bai Lu. “Interaction between BDNF and Serotonin: Role in Mood Disorders.” Neuropsychopharmacology 33, no. 1 (2007): 73–83.
  9. Hashimoto, Kenji, Eiji Shimizu, and Masaomi Iyo. “Critical Role of Brain-Derived Neurotrophic Factor in Mood Disorders.” Brain Research Reviews 45, no. 2 (2004): 104–14.
  10. Groves, J O. “Is It Time to Reassess the BDNF Hypothesis of Depression?” Nature News. Nature Publishing Group, August 14, 2007.

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