This post was written by one of our contributors; GP – John Sykes
“If you exercise more your mood will improve.”
This is a message most of us have already heard. Exercise is promoted as an efficacious part of holistic treatment in guidelines for various mental health conditions, including depression. Practitioners can be forgiven for feeling like they are selling the patient short with this advice, as it is not easy to find the enthusiasm to start increasing exercise when that individual may already be lacking in motivation and energy. However, the evidence for activity and exercise being beneficial for low mood is pretty overwhelming, and as a result, experts argue that there needs to be a greater drive to make exercise treatments accessible to those with mental health conditions.
How big a problem is depression?
Depression is very common in the UK with 1 in 4 women and 1 in 10 men requiring treatment for depression in their lives. 1 It is thought to be one of the greatest causes of disability worldwide and there is evidence that inadequate treatment of this condition is widespread. 2,3 Depressive disorders are also associated with an increased risk of other medical conditions, increased healthcare costs and increased risk of premature death. 4
What is depression?
Depression is a condition in which someone has pervasive low mood as well as other symptoms of depression each day for at least two weeks. Other key symptoms include marked loss of interest or pleasure in activities or things that previously brought enjoyment, poor sleep, change in appetite, tiredness, agitation, poor concentration, feelings of worthlessness or inappropriate guilt. Some people experience thoughts of self harm or suicide. Depression may range from mild to severe but the impact it can have on that individual should not be underestimated.
Pathophysiology of Depression
The precise mechanism of depression is not known. There seems to be strong association with genetics, as family, twin and adoption studies have shown, however no single gene has been implicated. 5 Individual specific environmental effects such as life trauma, low social support and family problems certainly play a strong role. There also seems to be a strong association between higher stress levels, as well as the presence of inflammatory markers such as interleukin-1a, tumour necrosis factor-alpha and interleukin-6, which are thought to activate stress pathways and impair the central serotonin system. 6 Those with major depressive disease have been shown to have lower levels of serotonin, noradrenaline and dopamine. The majority of drug medications used to treat depression act to increase levels of these monoamines, which adds further weight to this theory. 7 There are many other potential theories for the pathophysiology of depression, including impaired circadian rhythm and dysfunction of specific brain regions, but no one cause or theory of the above has been decided on. Basically, its complex!
How does Exercise work in reducing depression?
Physical fitness appears to confer resilience, which is defined as “the ability to withstand, recover and grow in the face of stressors and channelling demands”. This seems to serve as a stress resistant resource for both physical and mental health. This theory has been tested in cross-sectional and prospective studies that show those with high exercise levels have fewer health problems when they encounter stress. 8 Here are some of the possible biological mechanisms underlying these benefits:
Blunting or optimising neuroendocrine stress (HPA and SNS) – Chronic stress leads to dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic nervous system and the immune system. Physical fitness appears to serve as a buffer against this chronic stress. 9 It does so by attenuating the response of the HPA axis to chronic stress by reducing cortisol production and reduce noradrenaline release. Both the HPA axis and the sympathetic nervous system have an impact on immune function, which when corrected by exercise, shows to have positive effect on immune function too.
Reducing inflammation – Physical activity is known to cause an anti-inflammatory state. It has this effect by reducing levels of visceral fat in the body, which reduces production of inflammatory proteins. Physical activity also has a role in stimulating the production of anti-inflammatory cytokines from skeletal muscle, which creates a cascade of protein signalling that acts to reduce inflammation. Lower levels of chronic inflammation are evidenced by reduced levels of ‘C-reactive protein’ (CRP) in those who exercise more frequently. 10
Increasing growth factor expression and neural plasticity – There are four potential mechanisms which appear to play a role in growth factor expression and neural plasticity. Exercise increases -endorphin, vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF) and serotonin, which all play a role in reversing decreased rates of neurogenesis, another mechanism postulated to be responsible for a depressed mood. 10
Modulation of the endocannabinoid system – Increased levels of the proteins which stimulate cannabinoid receptors following exercise suggest this pathway is being upregulated, which is thought to act reduce pain, increase sedation and reduce anxiety. 10
Do the studies prove exercise as an effective treatment?
A comprehensive meta-analysis review of 25 studies investigating exercise as a treatment, which made adjustments to remove potential bias in the research revealed large and significant antidepressant effects of exercise. 11 One of the most recent randomised controlled trials found that a 12-week exercise program reduced the severity of symptoms of 53 participants with major depressive disorder, who also reported better wellbeing overall and fewer sleep related symptoms. 12
Can exercise prevent depression in the first place?
A large meta-analysis study looked at 49 studies with over 266,000 patients who were free of depression or depressive symptoms at baseline and were followed up for an average of around 7 years. 13 It was found that physical activity consistently protected against the risk of depression and that higher levels of physical activity were associated with a lower risk of developing depression or depressive symptoms. Interestingly, the positive effect of exercise was seen across all age groups and across several geographical locations all around the world.
There is impressive evidence to suggest that being fit actually confers a benefit to reduce the risk of depression. Over 1 million participants without any psychiatric diagnosis at baseline had their cardiorespiratory fitness measured and they were assessed for depressive symptoms during the study follow up period which ranged from 1 to 40 years. Those with low fitness levels had a 75% increased risk of depression and those with medium fitness level had an increased risk of 23%. 14 This suggests that it is not just beneficial to be active but also to be physically fit as well.
The HUNT Cohort study has provided further insight into the protective effects of exercise. Over 33,000 adults who initially had no symptoms of mental health disorder or physical health problems were followed up over an 11-year period. They proposed that 12% of future cases of depression could have been prevented if all participants took part in at least 1 hour of physical activity a week. This recommendation is very encouraging as 1 hour per week is much less than what is recommended by the national guidelines, showing the potential for a large benefit even from a small amount of activity. 15
How does exercise compare to medication?
Exercise as a treatment may be as effective as antidepressant medications. 16
The SMILE study conducted from 2000 to 2005 compared treatment in four groups: supervised exercise in groups; home-based exercise; antidepressant medication; or placebo pill for 16 weeks. All treatment groups had lower depression scores after the treatment period. The remission rate for supervised exercise was 45% compared to 47% in the medication groups, showing very similar effects of the intervention. 17 One year follow up of
this study revealed an increase in remission for exercise participants to 66% and regular exercise during the follow up period predicted reduced depression scores. 18
Some research demonstrates antidepressants offer limited efficacy with remission rates of up to 30% and many sadly cannot tolerate these medications due to side effects. 19,20 It is important to note that medication can be incredibly important in the management of various levels of depression and should never be ignored or neglected in a treatment plan in place of just exercising. The evidence is encouraging as it suggests exercise can be added to management plans for depression alongside standard treatment.
What if exercise is used alongside medication?
Multiple studies have shown an overwhelming benefit of exercise when used in addition to antidepressant medication. This includes studies of varying length using many different forms of activity from light activity and low intensity aerobics to high intensity aerobics and strength training. 16 Higher intensity workouts seemed to show the greatest improvements.
What about resistance training?
A meta-analysis that looked at 44 clinical trials including over 1800 participants shows that resistance exercise training was associated with a significant reduction in depressive symptoms regardless of patients age, sex or health status. The effect was also seen regardless of program duration, session duration, intensity, frequency or total prescribed amount of
resistance exercise across the different studies. 21
Last thoughts on exercise, mental health and wellbeing
People who exercise regularly report a higher quality of life and improved health status – both physically and mentally. 9,22 The relative increases in cardiorespiratory fitness and habitual physical activity are dose dependably associated with greater emotional well-being and lower depressive symptomology in both men and women. 23 Studies have also shown the negative impact of withdrawing or reducing activity, leading to lower mood and an increase in depression symptoms. 24,25 The impact of someone who regularly exercises stopping for just a 2 week period results in increasing depression symptoms, which correlates inversely with their fitness levels. 25
Summary
Given how common depression is in the UK and how effective physical activity appears to be, it is essential that this treatment form is promoted for patients, regardless of their health status, sex or age. 26 It is my hope that healthcare practitioners have the knowledge, confidence and evidence to encourage their patients to partake in regular exercise alongside standard medical treatment.
References
(1) Patient uk – https://patient.info/health/depression-leaflet
(2) Lopez AD, Mathers CD, Ezzati M et al.Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet 2006;367:1747-57.
(3) Kessler RC, Berglund P, Demler O et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 2003;289:3095-105.
(4) Schuch et al 2018 Physical Activity and Incident Depression: A Meta-Analysis of Prospective Cohort Studies. Am J Psychiatry. 2018 Jul 1;175(7):631-648. doi: 10.1176/appi.ajp.2018.17111194. Epub 2018 Apr 25.
(5) Sullivan PF, Neale MC, Kendler KS. Genetic epidemiology of major depression: review and meta-analysis. Am J Psychiatry 2000;157:1552-62.
(6) Hasler. Pathophysiology of depression: do we have any solid evidence of interest to clinicians? World Psychiatry 2010;9:155-161
(7) Belmaker RH, Agam G. Major depressive disorder. N Engl J Med 2008;358:55-68.
(8) Gerber M, Puhse U. 2009 Review article: do exercise and fitness protect against stress-induced health complaints? A review of the literature. Scand. J. Public Health 37, 801–819. (doi:10.1177/1403494809350522)
(9) Silverman and Deuster. Biological mechanisms underlying the role of physical fitness in health and resilience. Interface Focus. 2014 Oct 6;4(5):20140040
(10) Rethorst CD, Wipfli BM and Landers DM. The Antidepressive Effects of Exercise: A Meta-Analysis of Randomised Trials Sports Med 2009; 39 (6): 491-511 0112-1642/09/0006-0491
(11) Schuch FB, Vancampfort D, Richards J, et al: Exercise as a treatment for depression: a meta-analysis adjusting for publication bias. J Psychiatr Res 2016; 77:42–51
(12) Gerber M, Minghetti A, Beck J, Zahner L and Donath L. Is improved fitness following a 12-week exercise program associated with decreased symptom severity, better wellbeing, and fewer sleep complaints in patients with major depressive disorders? A secondary analysis of a randomized controlled trial. J Psychiatr Res 2019 Jun;113:58-64. doi: 10.1016/j.jpsychires.2019.03.011. Epub 2019 Mar 15.
(13) Schuch FB, Vancampfort D, Firth J, Rosenbaum S, Stubbs B et al. Physical Activity and Incident Depression: A Meta-Analysis of Prospective Cohort Studies. Am J Psychiatry 2018 Jul 1;175(7):631-648. doi: 10.1176/appi.ajp.2018.17111194. Epub 2018 Apr 25.
(14) Schuch FB, Vancampfort D, Sui X, et al: Are lower levels of cardiorespiratory fitness associated with incident depression? A systematic review of prospective cohort studies. Prev Med 2016; 93: 159–165
(15) Harvey SB, Overland S, Hatch SL, Wessely S, Mvkletun A, Hotopf M. Exercise and the Prevention of Depression: Results of the HUNT Cohort Study. Am J Psychiatry 2018 Jan 1;175(1):28-36. doi: 10.1176/appi.ajp.2017.16111223. Epub 2017 Oct 3.
(16) Netz Y. Is the Comparison between Exercise and Pharmacologic Treatment of Depression in the Clinical Practice Guideline of the American College of Physicians Evidence-Based. Front Pharmacol. 2017 May 15;8:257. doi:10.3389/fphar.2017.00257. eCollection 2017.
(17) Blumenthal et al. Exercise and Pharmacotherapy in the Treatment of Major Depressive Disorder. Psychosom Med. 2007 ; 69(7): 587–596. doi:10.1097/PSY.0b013e318148c19a.
(18) Hoffman et al. Exercise and Pharmacotherapy in Patients with Major Depression: One-Year Follow-Up of the SMILE Study. Psychosom Med . 2011 ; 73(2): 127–133. doi:10.1097/PSY.0b013e31820433a5.
(19) Sinyor, M., Schaffer, A., Levitt, A., 2010. The sequenced treatment alternatives to relieve depression (STAR*D) trial: a review. Can J Psychiatry 55:126-35.
(20) Gartlehner, G., Gaynes, B. N., Forneris, C., Amick, H. R., Asher, G. N., Morgan, L. C., et al. (2016). Comparative benefits and harms of antidepressant, psychological, complementary, and exercise treatments for major depression: an evidence report for a Clinical Practice Guideline from the American College of Physicians. Ann. Intern. Med. 164, 331–341. doi: 10.7326/M15-1813
(21) Gordon BR, McDowell CP, Hallgren M, Meyer JD, Lyons M, Herring MP. Association of Efficacy of Resistance Exercise Training with Depressive Symptoms: Meta-analysis and Meta-regression Analysis of Randomised Clinical Trials. JAMA Psychiatry. 2018 Jun 1;75(6):566-576. doi: 10.1001/jamapsychiatry.2018.0572.
(22) Fox KR. 1999 The influence of physical activity on mental well-being. Public Health Nutr. 2, 411–418. (doi:10.1017/S1368980099000567)
(23) Galper DI, Trivedi MH, Barlow CE, Dunn AL, Kampert JB. 2006 Inverse association between physical inactivity and mental health in men and women. Med. Sci. Sports Exerc. 38, 173–178. (doi:10.1249/ 01.mss.0000180883.32116.28)
(24) Nabkasorn C, Miyai N, Sootmongkol A, Junprasert S, Yamamoto H, Arita M, Miyashita K. 2006 Effects of physical exercise on depression, neuroendocrine stress hormones and physiological fitness in adolescent females with depressive symptoms. Eur. J. Public Health 16, 179–184. (doi:10.1093/ eurpub/cki159)
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