Elsevier

Biological Psychology

Volume 133, March 2018, Pages 79-84
Biological Psychology

Exercise reduces depression and inflammation but intensity matters

https://doi.org/10.1016/j.biopsycho.2018.01.015Get rights and content

Highlights

  • Exercise intensity matters for management of depression, anxiety and stress.

  • Pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, CRP) examined as a mechanism.

  • Moderate intensity exercise reduced depression and TNF-α.

  • High intensity exercise increased stress and IL-6.

Abstract

Background

Exercise may help to mitigate symptoms of depression by reducing inflammation; however, little is known about the influence of exercise intensity on depressed mood.

Methods

In the present study, sixty-one university students were assigned to six weeks of high-intensity interval training (HIT), moderate continuous training (MCT), or no exercise (CON) during their academic term. We measured changes in depression, anxiety and perceived stress along with pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and C-reactive protein (CRP).

Results

Depression increased for CON, demonstrating how quickly mental health can decline for students during their academic term. In contrast, MCT decreased depression and pro-inflammatory cytokine TNF-α levels. Although HIT decreased depressive symptoms, it also increased perceived stress, TNF-α and IL-6 relative to MCT. This may be due to the higher level of physical stress evoked by the more strenuous exercise protocol.

Conclusions

Taken together, the results suggest that moderate-intensity exercise may be an optimal intensity of exercise for the promotion of mental health by decreasing TNF-α. This is critical for informing the use of exercise as medicine for mental health.

Introduction

Major depression is a common and potentially fatal disorder that represents the leading cause of disability worldwide (Moussavi et al., 2007). The prevailing treatment for depression is a class of drugs known as selective serotonin re-uptake inhibitors (SSRIs) (Nutt et al., 1999); however, SSRIs are only fully effective for one third of depressed patients (Fava & Davidson, 1996). This underscores the critical need for new therapeutic approaches. Inflammation has been identified as a potential contributor to the development of depression (Miller & Raison, 2016), suggesting that anti-inflammatory therapeutics, such as regular physical exercise (Cotman, Berchtold, & Christie, 2007; Gleeson et al., 2011), may be effective at preventing and managing depressive symptoms. However, the optimal intensity of exercise has not been established and this information is critical when determining a prescription. The present study examined the effect of two predominant exercise training protocols: moderate continuous training (MCT) and high-intensity interval training (HIT), on depressive symptoms and pro-inflammatory cytokines in sedentary university students who are known to be at a high risk of developing depression (Ibrahim, Kelly, Adams, & Glazebrook, 2013).

Acute and chronic increases of pro-inflammatory cytokines cause a range of sickness behaviors that overlap with the symptoms of major depression including anhedonia, decreased activity, and social withdrawal (Dantzer, O'Connor, Freund, Johnson, & Kelley, 2008; Reichenberg et al., 2001; Shakhar & Shakhar, 2015; Suarez, Lewis, Krishnan, & Young, 2004; Wright, Strike, Brydon, & Steptoe, 2005). The two key pro-inflammatory cytokines implicated in sickness behavior and its associated depressive symptoms are tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) (Dantzer et al., 2008; Dantzer, 2001; Bluthe et al., 1994). When these cytokines are peripherally injected into the blood (Bluthe et al., 1994), they enter the brain, activate microglia, and amplify cytokine activity (Frank, Baratta, Sprunger, Watkins, & Maier, 2007). This causes changes to neurotransmitter metabolism, neuroendocrine function, and behavioral symptoms that are common in individuals with major depression, suggesting that they may contribute to the etiology of the disorder (Bluthe et al., 1994; Dantzer et al., 2008; Frank et al., 2007; Miller, Maletic, & Raison, 2009). Another pro-inflammatory cytokine associated with depressive symptoms is interleukin-6 (IL-6), which is elevated in individuals with SSRI-resistant depression (O’Brien, Scully, Fitzgerald, Scott, & Dinan, 2007). However, peripherally injecting IL-6 into the blood does not induce depressive symptoms (Brebner, Hayley, Zacharko, Merali, & Anisman, 2000). Unlike TNF-α and IL-1β, IL-6 is produced by skeletal muscle (Pedersen & Febbraio, 2008) and is elevated up to 100 times compared to baseline levels following strenuous exercise (Fischer, 2006). This acute increase in IL-6 from exercise has been shown to inhibit the production of TNF-α (Starkie, Ostrowski, Jauffred, Febbraio, & Pedersen, 2003), suggesting that it may have anti-inflammatory properties in the context of exercise (Gleeson et al., 2011; Pedersen and Febbraio, 2008). Critically, this may be a potential mechanism through which exercise may reduce depressive symptoms. Another inflammatory marker, C-reactive protein (CRP) is produced by hepatocytes in response to increases in IL-6, along with TNF-α, and IL-1β (Rattazzi et al., 2003). CRP is elevated in individuals with higher levels of perceived psychological stress (McDade, Hawkley, & Cacioppo, 2006) and lower levels of positive emotional well-being (Ironson, Banerjee, Fitch, & Krause, 2018), suggesting that it may play a role in the development of depressive symptoms from chronic stress.

Although pharmacotherapeutic approaches designed to reduce these pro-inflammatory cytokines (e.g., TNF-α antagonist etanercept) may help prevent and manage depression (Tyring et al., 2006), cytokine antagonist pharmaceutical drugs may not be suitable for individuals who are otherwise healthy. Instead, regular physical exercise (and its anti-inflammatory properties) may be a viable non-pharmacotherapeutic alternative for reducing depressive symptoms caused by inflammation. Indeed, prior randomized controlled trials have established that exercise can reduce depression (Mead et al., 2009; Nabkasorn et al., 2006) and anxiety (Wipfli, Rethorst, & Landers, 2008) in healthy populations. In clinical populations with chronic inflammatory diseases, regular aerobic exercise reduces depression (Perna et al., 2010) and inflammation (Goldhammer et al., 2005). In clinically depressed individuals, aerobic exercise reduces depressive symptoms (Mead et al., 2009; Rethorst et al., 2013), especially in those with high levels of TNF-α (Rethorst et al., 2013).

However, surprisingly little is known about the effects of exercise on inflammation in non-clinical populations who may be at risk of developing depression. To our knowledge, only two studies (Kop, Weinstein, Deuster, Whittaker, & Tracy, 2008; Poole, Hamer, Wawrzyniak, & Steptoe, 2011) have examined exercise, inflammation and depressive symptoms in non-clinical populations. Both studies recruited non-depressed individuals who engaged in regular physical exercise and examined the impact of withdrawing exercise for two weeks on mood (not depression per se) and cytokines levels. Although both studies reported a decrease in mood among the exercisers who had to withdraw from exercising, the cytokines results were less clear. One study found that IL-6 decreased after two weeks of not exercising, possibly due to the reduced release of IL-6 from the skeletal muscle (Poole et al., 2011); they also found no change in TNF-α, or in anti-inflammatory cytokines interleukin 1 receptor antagonist (IL-1ra) or interleukin 10 (IL-10). In contrast, the other study found no effect on IL-6 or CRP after two weeks of not exercising (Kop et al., 2008). Critically, neither study examined the effects of increasing exercise in sedentary individuals to prevent the development of depressive symptoms.

When evaluating whether exercise is a viable approach for reducing depressive symptoms, it is critical to determine the optimal intensity. Although there is evidence for the benefits of moderate-intensity exercise for reducing both depression (Dunn, Trivedi, Kampert, Clark, & Chambliss, 2005) and inflammation (Goldhammer et al., 2005; Thompson et al., 2010), engaging in a new exercise program can be challenging for sedentary individuals. The recent rise in popularity of high-intensity interval training (HIT) may be more appealing due to its shorter time commitment for similar physiological benefits (Gibala et al., 2006). HIT has also been shown to induce greater functional adaptation of the immune system in athletes (Born, Zinner, & Sperlich, 2017). Furthermore, recent work from our group shows that previous sedentary young adults found HIT to be more enjoyable than traditional forms of moderate-intensity continuous training (MCT) after six weeks (Heisz, Tejada, Paolucci, & Muir, 2016). Indeed, with respect to inflammation, greater release of IL-6 induced by more intense protocols like HIT (Fischer, 2006) may inhibit the production of TNF-α to a greater degree (Petersen & Pedersen, 2005; Starkie et al., 2003) for stronger anti-depressive effects than moderate intensity exercise. However, with respect to mood, there have been equivocal results, and some evidence suggests that HIT may be too strenuous to improve the mood of sedentary individuals and instead, may actually decrease it (Oliveira, Slama, Deslandes, Furtado, & Santos, 2013); that said, the effect of HIT on depression has not been assessed.

The present study examined the effect of six weeks of exercise training on mental health and pro-inflammatory cytokines in university students who are known to be at a higher risk of developing depression than the general population (Ibrahim et al., 2013). During their academic term, the students were randomly assigned to one of three groups: 1) moderate-intensity continuous training (MCT) group, 2) high-intensity interval training (HIT) group, or 3) no training control group (CON). Before and after the intervention, we measured changes in resting-state pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, CRP) and depressive symptoms as well as other associated changes in anxiety and perceived psychological stress (Beiter et al., 2015). We hypothesized that students would have higher perceived psychological stress than population norms (Cohen & Janicki-Deverts, 2012), and that this would be accompanied by increases in depression, anxiety and pro-inflammatory cytokines in the controls. MCT was hypothesized to decrease depressive symptoms and pro-inflammatory cytokines relative to CON; however, it was unclear whether HIT would be similarly effective as MCT at decreasing both depressive symptoms and pro-inflammatory cytokines.

Section snippets

Participants

Sixty-one healthy young adults (72% female) were recruited from McMaster University. Participants were students who met the inclusion criteria of: being a young adult aged 18–30 years old, and partaking in no more than one hour of vigorous physical activity per week prior to joining the study. Participants were stratified by sex and randomly assigned to one of three intervention groups: 1) High-intensity interval training (HIT) group, 2) Moderate-intensity continuous training (MCT) group and 3)

Mental health

Fig. 1 displays the change in depression, anxiety and perceived stress scores across the six-week intervention for the three groups. Table 1 presents pre and post intervention scores for each of the mental health variables. Depression decreased following MCT (p = 0.005, Cohen’s d = 0.83) and HIT (p = 0.012; Cohen’s d = 0.73) relative to CON, but the changes following MCT and HIT were not significantly different from each other (p = 0.77) [main effect of group, F(2, 52) = 5.92, p < 0.01;

Discussion

Exercise may help to mitigate symptoms of depression by reducing inflammation. Until now it has been unclear whether the exercise intensity matters. Our results suggest that it does and that moderate-intensity continuous exercise may be an optimal intensity when prescribing exercise as medicine for mental health.

We assessed university students during their academic term. This demographic is known to be at a higher risk of developing depression (Ibrahim et al., 2013) because of their

Financial disclosures

The authors declare no competing financial interests.

Acknowledgements

This research was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant 296518 to JJH, and NSERC Canada Graduate Scholarship to EMP. DMEB is the Canada Research Chair in Aging and Immunity. DL is the recipient of a CIHR Canada Graduate Scholarship.

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