# Exercise as it relates to Disease/Can lowering inflammation through exercise be used as an effective treatment for depression?

This article examines the impact exercise intensity has on mitigating depressive symptoms by reducing inflammation
Key Terms:
* Tumor Necrosis Factor-α (TNF-α)
* Interleukin 6 (IL-6)
* High Intensity Training (HIT)
* Moderate Intensity Training (MCT)
* Non-exercise Group or Control (CON)

## What is the background to this research?

This study examines whether exercise intensity effects the efficacy of exercise intervention in reducing depressive symptoms by lowering inflammation in non-clinical populations. Specifically, the research assesses cytokine activity in exercised student sample groups and concludes that moderate intensity continuous exercise is more effective at reducing inflammation caused by depressive symptoms than high-intensity. While there is a significant amount of research studying the positive impact that regular exercise has on negative mood states including depression and anxiety in clinical populations, this study fills a gap in the literature by using exercise intensity as an independent variable and makes an important contribution to the research regarding the prescription of exercise intervention to achieve better mental health outcomes.

## Where is the research from?

The research was conducted at McMaster University, all four authors are reputable academics. Two of the authors, Emily M Paolucci and Jennifer J. Heisz have published a number of dissertations in the fields of health science, kinesiology, neurological and mental health. The authors Dessi Loukov and Dawn M.E Bowdish are experienced pathologists and their research is mainly in the field of molecular medicine.

## What kind of research was this?

This study is a randomised control trial (RCT). RCTs are widely considered to produce the highest evidentiary level on the efficacy of healthcare interventions.

## What did the research involve?

The study involved a six-week exercise intervention program and measuring its effects on pro-inflammatory cytokines and mood disorders. The study participants were sixty-one adult university students from McMaster University between 18-30 years old (72% Female).
Participants were randomised into three groups, all of them completed 18 bouts of exercise;
* High-Intensity-Interval-Training(HIT) group (18 Students; 72% females);
* Moderate-Intensity-Continuous-Training(MCT) group (19 students; 68% female);;
* Non-Exercise/Control(CON) group(18 students; 72% females).
Limitations from the research design methodology;
Firstly, the study relies on the assumption that there is an inverse causal relationship between inflammation and the development of depression symptoms.
Secondly, the authors selected a small sample group with a high gender bias (female) comprised of individuals from student populations (not representative or randomised), none of whom suffer clinical mood disorders. Problematically, the researchers purport to generalise conclusions from the subject group data to the general population, without clearly stating the relationship between the sample group and the general population or highlighting any obvious difficulties in extrapolating the results more broadly.
Thirdly, the study measured the participants’ mental health and assessed particular symptoms of depression and anxiety using the Beck Depression Inventory II & Beck Anxiety Inventory respectively. However, because both inventories, which consists of 21 self-rating items, are, crucially, designed to assess the severity of a particular symptom of depression and anxiety in clinical populations, they may not be suitable to assess nuanced psychological changes in a healthy population sample.
Finally, the experiment showed outcome biases as it only examined four pro-inflammatory cytokines related to inflammation and depression. The study also failed to test hormones released during exercise that may impact inflammation and depression.

## What were the basic results?

According to these results TNF-α significantly decreased following MCT compared with CON, However TNF-α did not differ significantly between CON to HIT. IL-6 drastically increased post exercise relative to CON and MCT, however comparing CON to MCT there were only minor changes in IL-6. IL-6 and TNF-α were relatively higher in the CON group, therefore it can be said according to this table that both TNF-α will decrease more post MCT bouts, whereas IL-6 will increase post HIT relative to MCT. The finding also emphasised that when IL-6 is released via skeletal muscle it will have an anti-inflammatory response. In non-exercised individuals showing depression had elevated IL-6 levels which had mainly pro-inflammatory properties.

##### TABLE 1

The CON group recorded unusually high levels of stress which led to more depressive symptoms throughout the six-weeks. Pro-inflammatory cytokines such as TNF-α and IL-6 were elevated in the CON group in comparison to the MCT and HIT, however TNF-α did not decrease as meaningfully in the HIT group relative to the MCT group. The researchers attributed this high perceived stress that can be associated with high intensity styles of exercise. The article suggested that moderate-intensity-training may be optimal in reducing stress, inflammation and thus decreasing depressive symptoms as lowering TNF-α was accepted as producing better mental health outcomes. The article mainly focuses on elevated levels of pro-inflammatory cytokines such as TNF-α, IL-6, IL-1β in depressed individuals, most competing articles would agree however some suggest there are no changes in IL-6 when comparing peoples who are depressed and healthy.
For example, in contrast with the authors’ results, The National Centre for Biotechnology Information (NCBI) conducted similar research using exercise intervention which showed a decrease in pro-inflammatory cytokines such as IL-6 in depressed patients. The study's results displayed in Table two, indicated that pro-inflammatory IL-6 levels were inconsistent in the patients displaying depressive moods, and reported no difference in relation to IL-6 levels in their healthy patients. The NCBI study goes on to suggest that evidence supporting the proposition IL-6 is casually related to depression remains inconsistent, as far too many studies have generated quantitative results opposing this conclusion.

##### TABLE 2
## What conclusions can we take from this research?

Most scientific literature supports the proposition that exercise programs in general are effective at lowering pro-inflammatory cytokines and in turn contribute to a reduction in depressive symptoms, however evidence regarding the optimal exercise intensity remains equivocal. In addition to the methodological limitations, the researchers fail to account for other physiological factors that reduce cytokines when exercising, such as the release of endorphins.
Relevantly, a study conducted by the Journal of Affective Disorders conducted a similar experiment over six weeks and also measured β-endorphins levels amongst three test groups;(1) HIT exercisers;(2) MCT exercisers and a control group. The researchers found β-endorphin levels were highest in the post HIT exercisers relative to the MCT exercisers, and concluded that low to moderate exercise did not yield an endorphin release.
The study concluded that the patients subject to high intensity bouts of exercise had the highest reduction in depressive symptoms as well. The study used the Hamilton Depression Rating Scale (HAM-D), which saw a 77% reduction from baseline for the HIT exercisers compared to the MCT group that experienced a 65% decrease.
Notwithstanding the limitations outlined above, this study is important in encouraging further research into the possible impact of exercise intensity on mental health outcomes. It is recommended that researchers should design longitudinal studies with larger randomised sample groups to produce more reliable data on the efficacy of exercise on psychological well-being over time.

## Practical advice

* Start with simple exercise like walking or jogging
* Do what is enjoyable; team sports, exercise with friends, plan activities
* Stick to a routine
* Track your mood response to different intensity workouts
* Consult a doctor first
* Complete an APSS form prior to exercising.

## Further information/resources

* Beyond blue - https://www.beyondblue.org.au/
* Black Dog institute - https://www.blackdoginstitute.org.au/
* Head Space - https://headspace.org.au/
* ESSA (free Exercise and Mental Health ebook) https://exerciseright.com.au

## References

Add in the references using this code
* 1 2 3 4 5 6 7 8 9 10 11 Paolucci EM, Loukov D, Bowdish DME, Heisz JJ. Exercise reduces depression and inflammation but intensity matters [Internet]. 2018 Feb 3 [cited 2020 August 14]: 133:79-84. Available from database: https://www.sciencedirect.com/science/article doi.org/10.1016/j.biopsycho.2018.01.015
* ↑ 2.William P, Morgan MD. Anxiety Reduction Following Acute Physical Activity [internet]. 1979 Mar 1 [cited 2020 September 10]:9(3):36-45. Available from database: https://www.healio.com/psychiatry/journals/psycann/ doi.org/10.3928/0048-5713-19790301-06
* 1 2 Thiese M. S. (2014). Observational and interventional study design types; an overview. Biochem. Med. 24 199–210. 10.11613/BM.2014.022
* 1 2 Byrne A, Byrne DG. The Effect of Exercise on Depression, Anxiety and Other Mood States: A Review, In Journal of Psychosematic Research [internet].1993 Sep 6 [cited 2020 September 12]: 37:565-574. Available from database: https://www.sciencedirect.com/science/article/abs doi.org/10.1016/0022-3999(93)90050-P.
* ↑ Beck Depression Inventory (BDI) [Internet]. Washington DC, US, American Psychological Association, 2020. Construct: Depressive Symtoms; 2020 June 1 [cited 202 September 14]; about 2 screens], Available from: https://www.apa.org/pi/about/publications/caregivers/practice-settings/assessment/tools/beck-depression
* ↑ Cochrane Methods Bias [Internet]. [London, UK]: Julian Higgins and James Thomas; 2019. Cochrane Handbook for Systemic Reviews of Interventions, Chapter 10; 2020 [cited 2020 September 12]; [about 5 screens]. Available https://methods.cochrane.org/bias/reporting-biases
* 1 2 Zou W, Feng R, Yang Y. Changes in the serum levels of inflammatory cytokines in antidepressant drug-naïve patients with major depression [internet]. 2019 Jun 1 [cited 2020 Sep 14]:13(6). Available from database: https://www.ncbi.nlm.nih.gov/pmc/articles doi: 10.1371/journal.pone.0197267
* 1 2 3 Balchin R, Linde J, Blackhurst D, Rauch HG, Schonbachler G. Seating away depression? The impact of intensive exercise on depression [Internet]. 2016 August 1 [cited 2020 Sep 12]:200: 218-221. Available from database : https://www.sciencedirect.com/science/article/pii/ doi.org/10.1016/j.jad.2016.04.030
* ↑ Exercise Depression [Internet]. New South Wales, Sydney: Blackdog Institute, 2020. Exercise & Depression; 2020 Apr [cited 2020 September 13]; [about 2 screens]. Available from https://www.blackdoginstitute.org.au/wp-content/uploads/2020/04/5-exercise_depression.pdf
(if you have done the in-text referencing correctly, it will appear here - check the tips on Moodle for details, or of course the help options in wikimedia (or google it)
And add code in so this below appears (see Moodle - 2. Creating your page and editing tips - please look on this )