Physiological Effects of Exercise Training on

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to physical exercise induce physiological effects, which may account ... wait list controls, 1-3 mos of qigong exercise relieved anxiety (pooled SMD = 0.75; 95% ...
Physiological Effects of Exercise Training on Psychological Well-being Roland von Känel, MD

The International 22nd Puijo Symposium From Science to Clinical Practice IV – Neurodegenerative Diseases Kuopio, 27 June, 2014

Division of Psychosomatic Medicine & Department of Clinical Research

Prof. R. von Känel, MD

Types of psychological well-being addressed in this talk • Depression, depressive symptoms, and depression-like behaviours • Anxiety and anxiety-like behaviours • Stress: «feeling stressed» and the stress response Fundamental question to be addressed: Does chronic exposure to physical exercise induce physiological effects, which may account for feelings of depression, anxiety and stress?

Aerobic and resistance (aka metabolic) physical activity have more potent neuroplastic effects than other physical activity subtypes like stretching and relaxation: brain volume; functional activity in the prefrontal and hippocampal areas. Voelcker-Rehage & Niemann, Neurosci Biobehav Rev 2013

Exercise physiology and well-being

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Prof. R. von Känel, MD

Diagnostic Criteria: Major Depressive Disorder & Depressive Episodes Depressed mood or a loss of interest or pleasure in daily activities > 2 weeks Impaired function in social, occupational, and educational activities

At least 5 of 9 symptoms present nearly every day: 1. Depressed mood: e.g., feels sad or empty; appears tearful 2. Decreased interest or pleasure in most activities

3. Significant weight change (5%) or change in appetite 4. Change in sleep: Insomnia or hypersomnia 5. Change in activity: Psychomotor agitation or retardation 6. Fatigue or loss of energy 7. Inappropriate guilt or feelings of worthlessness 8. Diminished ability to think or concentrate, or more indecisiveness 9. Suicidality: Thoughts of death or suicide, or has suicide plan DSM-IV. American Psychiatric Association 1994 Exercise physiology and well-being

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Prof. R. von Känel, MD

Systematic reviews and meta-analyses on effects of exercise training on improvements in psychological well-being • Meta-analysis of 35 studies (1356 participants): compared with no treatment or control intervention, the pooled SMD for depression with exercise treatment was 0.62 (95% CI-0.81 to 0.42). As effective as antidepressant drugs. Cooney et al, Cochrane Database Syst Rev 2013

• Systematic review of 40 studies (2914 sedentary adults with a chronic illness): compared with no treatment, exercise training reduced anxiety symptoms by a mean effect of 0.29 (95% CI 0.23-0.36). Herring et al, Arch Intern Med 2010

• Systematic review of 8 RCTs for anxiety disorders: Exercise is effective as an adjunctive treatment for anxiety disorders. Less effective than antidepressants. Both aerobic and non-aerobic exercise seem to reduce anxiety symptoms. Jayakody et al, Br J Sports Med 2014

• Systematic review and meta-analysis of 7 RCTs (healthy adults): Compared to wait list controls, 1-3 mos of qigong exercise relieved anxiety (pooled SMD = 0.75; 95% CI 1.11 to 0.40) and stress (SMD = 0.88; 95% CI 1.22 to 0.55). Wu et al, BMC Complement Altern Med 2014 Exercise physiology and well-being

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Prof. R. von Känel, MD

Epidemiology: The link between poor psychological well-being and CVD risk is partially explained by exercise behavior with several candidate biological mechanisms accounting for this link

Stressed and depressed individuals report reduced physical activity levels which can explain about 25% of the association between stress / depression and CVD (HPA axis / ANS dysfunction; inflammation) Hamer, Psychosom Med 2012; Hamer et al, J Am Coll Cardiol 2008; Whooley et al, JAMA 2008; Hamer et al, Am J Geriatr Psychiatry 2011; Win et al, Heart 2011; Kamphuis et al, Med Sci Sports Exerc 2007 Exercise physiology and well-being

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Prof. R. von Känel, MD

Association of fitness with levels of atherosclerotic risk markers pre-exercise and post-exercise (e.g. Interleukin-6)

26 hypertensive, 40 normotensive subjects: 20 min of treadmill exercise at 70% VO2max

Inverse correlation between VO2peak and IL-6 at baseline, early and late post-exercise (p‘s A: total body fat mass, CRP

Donges et al, Med Sci Sports Excer 2010

Donges et al, Med Sci Sports Excer 2010

Yoga>A: Baroreceptor sensitivity Eyre & Baune, Brain Behav Immun 2014 Exercise physiology and well-being

Bowman et al, Eur J Clin Invest 1997

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Prof. R. von Känel, MD

Physiologic effects of chronic exercise on animal anxiety-like behaviours • Exercise could exert anxiolytic effects through promotion of anti-inflammatory, antioxidant, and neurothrophic activity in key brain regions (e.g. amygdala, hippocampus, locus coeruleus) with key role of IL-6. Moylan et al, Neurosci Biobehav Rev 2013; Salim et al, Adv Protein Chem Struct Biol 2012

• Induction of oxydative stress through glutathione depletion reduced open-field activity; this behavior did not occur after 2 wks of wheel-running (same effect as observed with an antioxydant) Salim et al, Behav Brain Res 2010

• Wheel-running increases hippocampal neurogenesis and BDNF expression; this effect seems to differently affect anxiety behaviours in rats: Decreased: Duman et al, Brain Res 2008 - Running engages local anxiety inhibiting mechanisms in the ventral hippocampus (e.g. GABA release): Schoenfeld et al, J Neurosci 2013

No change: Pietropaolo et al, Behav Neurosci 2006 Increased: Fuss et al, Hippocampus 2010 - Deletion of running-induced hippocampal neurogenesis by irradiaton prevents development of anxiety behaviour in mice: Fuss et al, PLoS One 2010

• Moderate regular (volunteer) activity seems anxiolytic, while excessive prolonged (forced) activity seems anxiogenic. Leasure & Jones, Neuroscience 2008 Exercise physiology and well-being

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Prof. R. von Känel, MD

A more holistic understanding of how exercise interacts with stress responses and psychological well-being • • • • •

Distraction from negative thoughts Improving self-esteem and self-efficacy Enhancing sense of self-mastery Providing opportunities for socialisation Reducing state anxiety in stress situations

Moylan et al, Neurosci Biobehav Rev 2013; Rimmele et al, Psychoneuroendocrinology 2009 Exercise physiology and well-being

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Prof. R. von Känel, MD

Exercise attenuates cardiovascular reactivity to stress: Attenuated BP increase in response to acute mental stress after exercise • • • • •

Meta-analysis of 15 studies: 500 individuals, aged 17-60 yrs 20-60 min of aerobic exercise (e.g. treadmill) Mental stress test between 10 min and 24 h after exercise bout Systolic BP increase:  4 mmHg Diastolic BP increase: 3 mmHg

Clinical relevance: a) BP lowering medications achieve on average 9 mmHg in SBP b) A decrease of 5 mmHg in SBP reduces mortality risk from myocardial infarction by 9% and from stroke by 14% Cardioprotection? Regular exercisers may show less of an increase in BP in response to daily hassles and stressors over a 24-h window. Hamer et al, Biological Psychology 2006; von Känel, J Hum Hypertens 2008 Exercise physiology and well-being

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Prof. R. von Känel, MD

Summary • The literature proposes a theoretical model of exercise as a modulator of the neuroimmune system with benefits for psychological well-being. • Different exercise subtypes might exert unique immunomodulatory and neuroplastic profiles.

• Need for comparative studies examining exercise subtypes from neuroplasticity and immune perspectives in depression and anxiety. • Rodent studies may help to better understand immunmodulatory mechanistics of exercise training. • Standardizing exercise interventions in terms of duration, intensity, and study populations (e.g. consider age-dependency of the immune system). • Clinical trials examinig immunmodulatory and neuroplastic effects of exercise should include biomarker assessments (e.g. PICs, BDNF). • In vivo microglial imaging techniques (PET has been utilized in depression). Eyre & Baune, Brain Behav Immun 2012, 2014; Moylan et al, Neurosci Biobehav Rev 2013 Exercise physiology and well-being

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