Review article
Does ceasing exercise induce depressive symptoms? A systematic review of experimental trials including immunological and neurogenic markers

https://doi.org/10.1016/j.jad.2018.02.058Get rights and content

Highlights

  • No trials studied exercise cessation related depressive symptoms (DS) in depression.

  • DS were significantly higher in female participants than in male participants.

  • DS arose without changes in neurotrophic or immune biological markers.

  • High-quality trials in healthy adults and patients with depression are needed.

Abstract

Background

Regular exercise in adults improves depressive symptoms (DS) and major depressive disorder (MDD), however the clinical effects of ceasing exercise are largely unknown.

Methods

Seven databases were searched from inception to December 2017. Eligibility criteria included English language studies investigating the effects of ceasing exercise on DS or MDD in regularly active adults with or without prior DS or MDD. Blood based markers related to exercise cessation (EC) were assessed, if recorded. Studies investigating exercise follow-up periods were excluded.

Results

No studies investigated EC in MDD. Six studies including two RCTS and three studies investigating neurogenic and immune biological markers associated with DS met inclusion criteria (152 healthy adults, females n = 50/32.89%). Compared to baseline, EC increased DS after three days, one week, and two weeks. Female participants had significantly more DS than male participants. Following EC, no changes in brain derived neurotrophic factor (BDNF) or tumour necrosis factor alpha (TNF) were evident, however C-reactive protein (CRP) at week one and interleukin 6 (IL6) at week two were reduced.

Limitations

Quality concerns including risks of attrition and reporting bias limit our confidence in these results.

Conclusions

Ceasing regular exercise increases DS in healthy adults, with greater DS in females than males. Contrary to the cytokine/inflammatory hypothesis of depression, DS were associated with reduced CRP and IL6 and without increased TNF. High quality trials are needed to extend this field of research in both healthy and MDD populations.

Introduction

Major Depressive Disorder (MDD) is a clinical syndrome characterised by low mood accompanied by a constellation of other depressive symptoms (DS) that are sustained for at least two weeks in accordance with diagnostic criteria such as the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 2013). DS can describe both symptoms of MDD that constitute a diagnosable episode of depression, as well as symptoms that do not. However MDD involves psychological symptoms of altered affect, anhedonia or the loss of pleasure in daily activities. Other features can include biological symptoms of appetite, weight, and sleep changes, reduced libido, and cognitive and somatic symptoms. Cognitive symptoms include poor attention, concentration, and memory or ‘pseudo dementia’, whilst somatic symptoms can include fatigue and increases in sensations of pain. Symptoms must be a change from previous function and include the key symptoms of depressed mood and loss of pleasure in daily activities to meet the criteria for MDD. MDD response rates to current pharmacotherapies are low, and up to 50–60% of patients with MDD demonstrate partial or inadequate responses (Fava, 2003), making the identification of alternate therapies a priority research concern, and the attenuation and prevention of DS an important public health issue.

Exercise has been widely investigated for reducing and preventing DS and MDD. Exercise is defined by the American College of Sports Medicine as “a subclass of physical activity… [that is] planned, structured, and repetitive bodily movement done to improve or maintain one or more components of physical fitness” and includes aerobic or cardiorespiratory exercise, strength training, and flexibility (American College of Sports Medicine, 2014). Exercise undertaken three times weekly for at least eight weeks has demonstrated efficacy for treating MDD (Perraton et al., 2010, Stanton and Reaburn, 2014), with effect sizes ranging from moderate (SMD −0.62, 95% CI: − 0.81 − 0.42) to large (0.82 95% CI − 1.12 to − 0.51) (Cooney et al., 2013, Mead et al., 2009, Schuch et al., 2016), although results from higher quality studies can be varied (Krogh et al., 2017). In addition, a mega-analysis of meta-analyses of high quality randomised controlled studies about physical activity for DS found physical activity reduced DS (− 0.50; 95% CI: − 0.93 to − 0.06) (Rebar et al., 2015, Teychenne et al., 2008). Indeed regularly exercising individuals show nearly 45% lower odds of having DS than their sedentary counterparts, and even low doses of activity (up to 150 min/week) can prevent DS in healthy adults (Pareja-Galeano et al., 2016, Teychenne et al., 2008). Both aerobic and resistance exercise programs reduce DS symptoms, although mixed programs can be significantly more effective than aerobic or resistance exercise alone (Rethorst et al., 2009). The efficacy of exercise for MDD and DS has seen the inclusion of exercise in clinical treatment guidelines for affective disorders (Malhi et al., 2015, National Institutes of Health and Care Excellence (NICE), 2016, Scottish Intercollegiate Guidelines Network (SIGN), 2010). Moreover current national and international public health physical activity guidelines for adults prescribe at least 150 min of moderate intensity exercise weekly to maintain health and prevent depression, or 75 min to 150 min of vigorous intensity exercise for added health benefits (Department of Health, 2017a, Department of Health, 2017b, Office of Disease Prevention and Health Promotion, 2017, World Health Organisation, 2017). Adequate physical activity and exercise are therefore important clinical and public health issues.

The clinical efficacy of exercise for improving DS and MDD may arise from the advantageous effects of exercise on monoaminergic function, neurogenesis, and immunity that are evident in rodent and human studies. Exercise involves changes in monoamine metabolism associated markers including monoamines, monoamine receptors, and transporters (Cotman et al., 2007, Ford, 2002, Kasapis and Thompson, 2005, Petersen and Pedersen, 2005, Valkanova et al., 2013), including low intensity (but not high intensity) exercise related activation of serotonergic neurons in the dorsal raphe nucleus (DRN) that are associated with reduced depression-like behaviours in rats (Nishii et al., 2017, Otsuka et al., 2016). During acute exercise, working muscles generate exponential increases in interleukin 6 (IL6) that blunts pro-inflammatory TNF expression, and increases the expression of the soluble TNF receptors, interleukin 10 (IL10), and the interleukin 1 receptor antagonist (IL1ra), with increases in C-reactive protein (CRP) up to 10 h later (Petersen and Pedersen, 2005). This suggests exercise related IL6 could prevent the aetiology of a pro-inflammatory environment via the blunting of TNF and increased IL10 expression. Collectively, the evidence about effects of exercise on DS and MDD suggests the effects of exercise may be mediated through exercise-induced changes in monoamine, neurogenesis, and immune functions.

On the contrary, it is reasonable to suggest that the cessation of exercise could have adverse effects on DS and MDD and related biological functions. Indeed the cessation of exercise has been shown to adversely affect mental health in humans (Weinstein et al., 2017), and the cessation of chronic exercise in mice has been shown to increase anxiety-like and impaired cognition-like behaviours alongside reductions in hippocampal neurogenesis (Kim et al., 2013, Nishijima et al., 2013). This suggests that the cessation of regular exercise in adults could increase DS and MDD. This systematic review of the literature aims to evaluate the published literature on the effects of ceasing regular exercise on DS in adults with or without prior DS or MDD.

Section snippets

Methods

This systematic review was conducted and reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Liberati et al., 2009) in the majority of respects. These include: the title; structured abstract; introductory rationale; objectives; eligibility criteria; information sources; search; study selection; data collection process; data items; risk of bias in individual studies; summary measures; synthesis of results; risk of bias across studies;

Study selection

Data base searches returned 945 reports and 14 additional reports were identified through Google Scholar. All articles were imported into Endnote software (version 8) where 512 duplicates were removed. Screening of titles and abstracts by J.A.M excluded 442 articles not investigating exercise cessation to produce a shortlist of 26 potential reports. The full text of these were then considered by J.A.M to ascertain whether they met the inclusion and exclusion criteria. Contact with authors

Summary of evidence

This systematic review of the literature has investigated the noteworthy and novel question of whether exercise cessation involves increases in DS. In the absence of literature investigating exercise cessation related DS in active patients with MDD or a history of MDD, this study has investigated the effects of ceasing exercise in healthy active adults. In support of our hypothesis, the controlled trials included in this review demonstrated the cessation of aerobic exercise for three days (

Acknowledgements

This research was supported by an Australian Postgraduate Award (to JAM) and Research Training Scholarship (to ATO) from the Australian Government.

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