Abstract
Major depression, bipolar disorder, and schizophrenia are severe mental illnesses. Despite receiving psychopharmacological and psychosocial treatments, about half of patients develop a chronic course with residual cognitive and negative symptoms and have a high risk for cardiovascular disease and reduced life expectancy. Therefore, add-on innovative treatment approaches are needed to improve outcome. Aerobic exercise interventions have been shown to improve global functioning, cognition, and negative and depressive symptoms in these patients. The basic mechanism of these exercise-related changes has been reported to be improved brain plasticity, e.g., increased volume of disease-related brain regions such as the hippocampus. The optimal type, duration, and frequency of exercise have not yet been determined and need to be addressed in supervised physical exercise studies. Because of the low physical activity levels, lack of drive related to negative and depressive symptoms, and high prevalence of cardiovascular comorbidities in patients with severe mental illness, besides aiming to improve symptoms of mental illness, exercise interventions should also aim to increase cardiorespiratory fitness, which they should comprehensively assess by direct measurements of maximal oxygen uptake. Based on the recommendations for developing cardiorespiratory fitness by the American College of Sports Medicine, 150 min moderate-intensity training per week or vigorous-intensity exercise training for 75 min per week are appropriate. Most studies have had relatively short intervention periods, so future studies should focus on long-term adherence to exercise by implementing motivational strategies supported by telemedicine and by identifying and targeting typical barriers to exercise in this patient population.
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Introduction
In 2010, more than 25% of the population in Europe was diagnosed with a mental illness [1]. Among mental illnesses, major depression (MDD), bipolar disorder (BD) and schizophrenia (SZ) belong to the 20 most burdensome disorders and result in annual costs of 207 billion euro in Europe. Thus, besides cardiovascular diseases [2, 3], mental disorders—especially MDD—are one of the leading illness-related causes of years lived with disability worldwide [4]. Furthermore, more than 50% of patients in Europe with a mental illness, equivalent to about 25 million Europeans, develop a relapsing, chronic course of their illness with residual symptoms, which are associated with poor functional outcome [5].
Epidemiological research showed that in the last 100 years the long-term outcome of SZ has remained relatively stable [6], despite the introduction of psychotropic medications 70 years ago. Furthermore, psychotropic medications also have not improved outcome dimensions like cognition or negative symptoms. Overall, about 20% of patients with SZ have a good outcome and are able to participate in the primary job market, maintain a stable partnership and have longer phases with no need for psychopharmacological support [7, 8]; about 30% of patients will have a good prognosis but will need to take long-term psychotropic medication, which can have burdensome side effects, especially related to metabolic syndrome [9]; and about 50% of patients will develop a chronic course (defined as continuous symptoms over a period of at least 2 years) with different degrees of residual symptoms and disability [5]. Residual symptoms include cognitive dysfunction, impaired mood, reduced drive, and reduced ability to cope with stress. These individuals have an unfavorable long-term social outcome, meaning that they have difficulties finding a long-term job on the primary job market or maintaining a stable partnership [8].
Besides having a direct influence on functional outcome, environmental risk factors also affect mortality: The mortality rate from physical causes, including suicide is 20-fold higher in patients with unipolar depression than in the general population, 15-fold higher in patients with BD, and 12-fold higher in patients with SZ [10,11,12,13]. Another important cause is the high incidence of medical comorbidities due to unhealthy lifestyle habits, such as high rates of cigarette smoking and low levels of physical activity. Estimates indicate that together suicides and lifestyle-related factors reduce life expectancy by nearly 10 to 20 years compared with the general population [14, 15].
A meta-analysis of data from 29 countries on 6 continents confirmed that people with mental disorders have a significantly higher mortality rate and that, in 65 studies, the highest mortality rate (relative risk 2.54; 95% CI 2.35–2.75) was among patients with psychosis [15,16,17,18]. People with severe mental illness have a higher risk of developing coronary heart disease than controls (adjusted hazard ratio 1.54; 95% CI 1.30–1.82) and a higher rate of autonomic nervous system dysfunction, including diminished heart rate variability, hypertension, alterations of the QT interval, and lipid pattern abnormalities [19]. Unfortunately, the currently available psychopharmacological and psychosocial treatments do not ameliorate or improve these symptoms significantly and therefore do not help to improve functional outcome or increase life expectancy.
Surprisingly few studies have examined whether aerobic exercise combined with diet and psychosocial interventions can reduce the mortality gap between patients with mental disorders and the general population, and the studies included only small samples of patients [20]. The seminal paper by the Lancet Commission [21] identified an unhealthy diet and a sedentary lifestyle as major risk factors for the physical illness burden of patients with MDD, BD, and SZ, diseases that are also collectively referred to as affective and nonaffective psychoses. The paper gives recommendations to influence these modifiable risk factors, e.g., including regularly exercise in treatment programs.
This qualitative review will outline the effects of aerobic exercise on clinical outcome in patients with MDD, BD, and SZ and will evaluate the quality of intervention studies on the basis of the requirements of modern sports medicine.
Physical activity, physical fitness, and medical health outcome in patients with MDD, BD, and SZ
Low physical activity levels and poor cardiorespiratory fitness (CRF) are associated with a high risk of cardiovascular disease and all-cause mortality [22]. Exercise and good CRF play an important role in mitigating cardiovascular disease risk factors, such as metabolic syndrome, which is defined as a combination of increased waist circumference; elevated fasting glucose, triglycerides, and low high-density lipoprotein cholesterol; and high blood pressure [23, 24]. A meta-analysis determined that the risk of metabolic syndrome was elevated in all patients with affective and nonaffective psychoses (32.6%, 95% CI 30.8–34.3%) and that the prevalence did not differ between patients with MDD, BD, or SZ [25].
Another meta-analysis found that patients with MDD had lower levels of physical activity (standardized mean differenc, − 30; 95% CI − 0.40 to 0.21) and higher levels of sedentary behavior (standardized mean difference 0.99; 95% CI 0.01–0.18) than healthy controls [26]. Therefore, researchers concluded that less physically active patients might benefit from specific aerobic exercise interventions aimed at increasing physical fitness [27]. An important aspect to consider in this context is that low physical activity is related to negative symptoms such as amotivation [28], so aerobic exercise interventions must be supervised by experienced sports scientists to ensure that patients adhere to the intervention [29].
Physical fitness and physical activity are low not only in patients with MDD, but also in those with BD [30]. However, this diagnostic group is highly underrepresented in physical activity studies.
A study in patients with SZ showed that low physical fitness was associated with a higher prevalence of metabolic syndrome and more severe cognitive, negative, and positive symptoms [27]. The exercise capacity (measured by the distance covered in the 6-min walking test) of patients with SZ and prediabetes was reduced and the body mass index was increased; in addition, patients with SZ and manifest type 2 diabetes were less physically active [31].
Previous aerobic exercise studies showed the feasibility of endurance training in patients with SZ, and adaptations to aerobic endurance training in patients were comparable to those in healthy controls, as assessed by physical working capacity and maximal achieved power. However, differences were detected in changes of performance at a lactate concentration of 3 mmol/L, i.e., patients with SZ showed an impaired increase in lactate [29].
Different types of interventions have been evaluated that aim to improve physical health in patients with mental illness. A meta-analysis of 47,231 patients with SZ summarized and compared the effects of pharmacological and nonpharmacological interventions [32]. The authors showed that the most effective interventions for weight reduction were individual lifestyle counseling and exercise interventions, followed by psychoeducation, augmentation with the atypical antipsychotic aripiprazole, topiramate add-on therapy, and dietary interventions. The best efficacy in reducing glucose levels was found for a switch from olanzapine (the atypical antipsychotic with the highest risk for metabolic syndrome) to aripiprazole and add-on medication with metformin. Efficacy was also shown for treatment with glucagon-like peptide-1-receptor agonists, dietary interventions, and aripiprazole augmentation. Insulin resistance improved best followed by metformin treatment. Metformin also had the greatest effects on total cholesterol and high-density lipoprotein cholesterol. The best effect on triglycerides and low-density lipoprotein cholesterol was achieved with topiramate. Importantly, only exercise interventions increase exercise capacity [32]. Recent efforts to increase the efficacy of exercise include the use of high-intensity interval training (HIIT). In a randomized controlled HIIT study, compliant patients with overweight and SZ showed improvement in waist circumference, negative symptoms, and psychosocial functioning [33]. HIIT may be a feasible and effective way to improve CRF and metabolic parameters and has been established as such in physical disorders. It may also have more beneficial effects on the metabolic state than more moderate and continuous endurance training methods [20].
Effects of aerobic exercise on symptoms of MDD
Aerobic exercise, often revered to as “endurance exercise”, is defined as physical activity with a predominant metabolic pathway that uses oxygen to meet energy demands (oxidative phosphorylation) and leads to only low blood lactate levels [34]. In practice, aerobic exercise is usually characterized by repeated sequences of physical activity in a light to moderate intensity for extended periods of time. Aerobic exercise improves especially CRF and includes typically activities such as walking, swimming or cycling [35]. Contrastingly, anaerobic exercise refers to short-term high-intensity efforts with a preponderance of metabolic pathways not using oxygen (phosphagens metabolic pathway and glycolytic pathway) [36]. In most studies, the term "anaerobic training" is used to describe high-intensity exercise intervals with a duration of up to several minutes that result in increased lactate levels.
Aerobic exercise studies addressing MDD are summarized in Table 1. An aerobic exercise training study of 12 × 75-min sessions over a period of 4 weeks in patients with SZ and MDD revealed improvements in cognition, which were more pronounced in the patients with SZ; however, the patients with MDD showed a greater reduction in depressive symptoms and anxiety [37]. Aerobic exercise studies in MDD showed that exercise improves working memory and psychosocial functioning and reduces depressive symptoms [38, 39]. In particular, one study provided evidence for an effect of aerobic exercise on remission in MDD by showing that 29.5% of patients with unremitted MDD remitted after 3 months of aerobic exercise treatment [40].
In a randomized, controlled trial, 50 min’ add-on supervised aerobic exercise training 3 times a week for 4 months decreased symptoms of depression, anxiety, and stress compared with pharmacotherapy with antidepressants [41]. After an 8-week walking or running aerobic exercise program in local sports clubs, patients with MDD showed a large reduction in depressive symptoms compared with patients on a waiting list [42]. Moreover, an 8-week study found that high-frequency exercise was superior to low-frequency exercise with respect to depressive symptoms [43]. In an unsupervised study of physical activity in patients with MDD given access to fitness center resources, an increase in moderate-to-vigorous activity was associated with improvements in depressive symptoms [44]. In an 8-week study both aerobic and non-aerobic training methods had favorable effects on depression scores [45].
Different types of exercise have been studied in the last decade. A meta-analysis revealed small effects of aerobic exercise and yoga in outpatients with MDD, whereas the effects of Tai Chi were insufficient to enable conclusions to be drawn [46]. Additionally, aerobic exercise was superior to basic body awareness therapy with respect to depressive symptoms and cardiovascular fitness [47]. In patients with MDD randomized to 4 weeks’ sprint interval training or continuous aerobic exercise training, improvements in CRF were observed in both groups and were associated with improved depressive symptoms, emotional wellbeing, and sleep [48]. In contrast, another study found no improvements in depression score in the Hamilton Rating Scale for Depression after a 4-month strength and aerobic exercise training in patients with MDD [49]. Using mendelian randomization methods on genomic and phenotypic data from the UK biobank, beneficial effects of exercise were detected in depression but not in SZ [50, 51] (Table 1).
Effects of physical activity on symptoms of BD
No interventional studies have examined the effects of exercise in patients with BD. However, in a study examining the effects of N-acetylcysteine treatment, physical activity was not related to improvements in depressive symptoms, although those participants who engaged in higher levels of physical activity had greater improvements in social and occupational functioning [52].
Aerobic exercise training improves cognition and symptoms in patients with SZ
Several studies have demonstrated beneficial effects of physical exercise on symptoms of SZ (Table 2). For example, a well-cited meta-analysis showed that in patients with SZ aerobic exercise improves negative, positive, and depressive symptoms and global functioning, as measured by the Global Assessment of Functioning (GAF) score [53]. In addition, another meta-analysis focusing on cognition demonstrated improved global cognition, working memory, social cognition, and attention after aerobic exercise in patients with SZ [54]. A recent meta-analysis of randomized controlled trials found that aerobic exercise had small beneficial effects on negative symptoms in patients with SZ [55]. Across aerobic exercise studies, symptom improvement was seen in interventions consisting of 90 min of moderate exercise per week [56]. This finding is in line with our own work, which showed that 3 × 30 min of aerobic exercise per week alleviated negative symptoms and significantly improved global functioning and short-term memory in patients with SZ [57, 58]. Moreover, we found preliminary evidence that the improvements in level of functioning might be sustained even after exercise cessation [59].
Effects of aerobic exercise on cognition have been observed also in patients with first-episode SZ. After a 12-week supervised circuit-training program, improvement was seen in processing speed, visual learning, and visual attention domains [60]. In 75 patients with SZ randomized to 12 weeks of either moderate-intensity treadmill exercise or stretching and toning exercise, aerobic exercise improved processing speed and attention [61]. However, in a pilot randomized controlled trial in a small sample, group aerobic exercise over 12 weeks showed similar improvements in cognition and symptoms as treatment as usual [62]. After patients with SZ performed 12 weeks of treadmill training, their general and psychopathology and total score on the Positive and Negative Symptom Scale (PANSS) and aerobic capacity improved [63]. In a 6-month randomized study comparing aerobic exercise with occupational therapy in patients with SZ, exercise reduced symptoms, depression, and need of care and increased cardiovascular fitness [64]. In contrast, after a single session of aerobic exercise and yoga, patients from both groups showed only decreased anxiety and psychological stress and increased subjective wellbeing [65]. In meta-analyses of meditation-based mind–body interventions, small effect sizes have been observed for yoga in SZ [66]. Besides yoga, other exercise interventions such as Tai Chi have been applied in SZ patients and led to improvements in PANSS score, negative symptoms, and aggressive behavior [67]. A study that compared a 12-week Tai Chi program with aerobic exercise showed improved negative and depression symptoms [68]. In a randomized 8-month study of a Greek traditional dancing program, the dancing group showed improved positive and negative symptoms, GAF score, and quality of life compared with a sedentary group [69]. Finally, resistance training was studied in patients with SZ and improved negative symptoms [70] and level of functioning assessed with the GAF [71] (Table 2).
Neuroplasticity effects of aerobic exercise
Animal models and basic research in humans clearly show that aerobic exercise has favorable neurobiological effects. These effects may involve epigenetic alterations, synaptic plasticity, differentiation of glial cells and neurogenesis, the hypothalamus–pituitary–adrenal axis, growth factors, immune-related mechanisms, neurotransmitters, and the endocannabinoid system [72]. In 2103 adults from the general population, CRF, measured as peak oxygen uptake (VO2peak), was related to higher gray matter volume and showed a strong association with gray matter volume of the left middle temporal gyrus, right hippocampus, left orbitofrontal cortex, and bilateral cingulate cortex [73]. A meta-analysis of hippocampal volume in 737 voluntary participants revealed significant positive effects of aerobic exercise on left hippocampal volume but not on total hippocampus volume [74]. These results may be relevant for MDD, BD, and SZ because these brain disorders have been repeatedly shown to involve structural and functional alterations in the hippocampal formation [75, 76]. Moreover, a 7-Tesla magnetic resonance imaging study in older adults found a prominent volume increase in the left cornu ammonis (CA) subregions of the hippocampus and a trend for a volume increase in the left CA4/dentate gyrus after physical activity [77].
Deficits in both episodic and working memory are related to hippocampal abnormalities and are hallmarks of an unfavorable outcome in MDD [78] and SZ [79]. Our first study to investigate the effects of aerobic endurance training in a small sample of patients with multi-episode SZ showed a significant 10% increase in hippocampal volume after 3 months [57]. In our subsequent study in 20 patients, which combined 3 months of aerobic endurance training with cognitive remediation, we found no changes in hippocampal volume in the exercise group [58], but we did find a significant correlation between exercise-related volume increases in the CA4/dentate gyrus subregion of the hippocampus and the SZ polygenic risk score (SZ-PRS, [80]). Using cell-specific PRS, we found that this volume effect in CA4 was also caused by oligodendrocyte precursor cell-related pathways [81], which is also in line with our post-mortem finding of reduced oligodendrocyte number in the CA4 subregion [82]. In SZ and MDD it has been hypothesized that metabolic coupling may link oligodendrocyte to interneuron pathology [83]. Other studies found no changes in total hippocampal volume after aerobic exercise in MDD [84] or SZ [85]. However, after a 12-week aerobic exercise training, hippocampal volume in the CA1 subregion increased in SZ patients, whereas hippocampal vascular volume was unchanged, indicating no effect of aerobic exercise on blood vessels [86]. Additionally, a study that compared aerobic exercise training with table soccer in patients with SZ and healthy controls showed an increased volume of the right entorhinal cortex compared with baseline after 6 weeks’ training [87] and of the left superior, middle, and inferior anterior temporal gyri after 3 months’ training; but patients with SZ who played table soccer showed increased volumes in the motor and anterior cingulate cortices [88]. After 6 weeks’ aerobic exercise training, a magnetic resonance spectroscopy study in patients with SZ found increased N-acetyl-aspartate/total creatine levels in the left dorsolateral prefrontal cortex in both the aerobic exercise and table soccer groups [89], indicating improved neuronal viability. Additionally, a 6-month aerobic exercise program improved the integrity of motor function-related white matter fiber tracts compared with a life-as-usual condition [90].
Taken together, these results indicate that in SZ exercise has neuroplastic effects in brain regions that are affected by the disease itself. The effects of aerobic exercise on brain volume changes and underlying mechanisms warrant further study, not only in patients with SZ but also in those with MDD and BD.
Improvements of CRF in patients with severe mental illness
CRF is an important marker of cardiovascular health and should be comprehensively assessed in both clinical studies and clinical practice [22]. Especially in patients with severe mental illness and negative symptoms such as reduced drive and motivation, CRF serves as a control for the efficacy of an exercise intervention. Because of the above-mentioned low activity levels and high prevalence of cardiovascular comorbidities in patients with severe mental illness, besides aiming to improve symptoms of mental illness exercise interventions should also aim to increase CRF [91].
Several studies have focused on changes of CRF in patients with MDD [42, 45, 47,48,49, 84, 92,93,94,95,96,97,98] (Table 1) and SZ (e.g. [99,100,101,102,103]) (Table 2). Some studies directly measured maximal oxygen uptake (referred to as VO2max or VO2peak) to test changes in CRF in patients with MDD [45, 48, 49, 92, 95, 97, 98] and SZ [57, 63, 64, 85, 90, 99, 100, 103,104,105,106]. These tests are considered the gold standard, but other tests indirectly assessing CRF have been applied. For example, rather than being directly measured by cardiopulmonary exercise testing, VO2max can be estimated by data from a maximal or submaximal stress test. This approach of estimating CRF was used in a few studies in MDD [42, 47, 84, 93] and one in SZ [61]. Submaximal proxy measures can also be used to estimate CRF, e.g., the 6-min walking test, 400-m walking test, and 3-min step test; some studies in SZ have used such tests [69, 101, 102, 107, 108]. Aerobic capacity or endurance capacity can also be measured by an exercise stress test without assessing oxygen uptake, an approach used in studies in MDD [96] and SZ [29, 58, 88].
Besides using different measurement methods, studies differ regarding the training modalities. To date, the effects of anaerobic exercise interventions have been investigated only scarcely. However, there are studies that combined aerobic and anaerobic training elements [90]. In addition, there is a growing body of studies investigating HIIT [33, 47, 98,99,100, 104], which is typically characterized by high-intensity exercise at 4 × 4 min intervals (85–95% of maximum heart rate [HRmax]), with active breaks consisting of 3 min of moderate-intensity exercise (approximately 70% of HRmax). HIIT was shown to be effective in improving CRF in patients with SZ. A small, 8-week study showed that VO2peak increased by 12% in the HIIT group (n = 12) but did not increase in the PC gaming group (n = 7) [104]. These results were confirmed by a recent randomized controlled trial on the effects of 12 weeks’ HIIT on VO2max in 21 patients with SZ. Like the study by Heggelund et al. [104], in this study the control group (n = 26) practiced their PC gaming skills. Although more than half of the patients in the HIIT group showed a significant increase in workload, a significant within-group difference in VO2max was only observed when the physical activity competence of the health care providers was added into the statistical model. This result underlines the importance of professional and experienced supervision when aiming to successfully improve CRF in patients with SZ [99]. The study findings are supported by a similar study in which the training group (n = 25) performed aerobic interval training and received professional adherence support twice a week over the 12-week intervention period. The patients’ VO2peak improved by 10%, while no change was observed in the control group (n = 23), who performed two supervised exercise sessions at the beginning of the study and were subsequently encouraged to continue exercising on their own [100].
To the best of our knowledge, only two studies have evaluated a form of interval training in patients with MDD. Gerber et al. [98] found associations between an increase in VO2max and improvements of symptoms in patients who performed a sprint interval training consisting of 25 repetitions of 30-s high-intensity bursts at 80% of maximal power output, followed by 30 s of total rest. Danielsson et al. [47] reported a significant increase of CRF in the intervention group, which performed intervals of exercise at higher perceived intensity during the aerobic exercise program, although training intensity was not strictly defined.
Exercise training of moderate intensity can also be effective in improving maximal oxygen consumption in patients with MDD [45, 92, 97] and SZ [29, 57, 63, 85, 105]. For example, in the most recent study in SZ, VO2max improved by 18% in patients after a 12-week aerobic exercise program with intensities ranging from 60 to 75% of HRmax (n = 16) but decreased by − 0.5% in the usual care group (n = 17) [105].
Mixed programs consisting of aerobic training combined with resistance training may also have the potential to improve CRF in patients with MDD [49, 94] and SZ [85, 102]. Although three studies measured CRF directly by cardiopulmonary exercise testing [49, 85, 94, 106], Korman et al. [102] used a submaximal test (they assessed functional exercise capacity, a submaximal proxy measure of CRF, as the distance walked during the 6-min walking test). Moreover, two studies that evaluated the effect of dancing programs in SZ showed improvements in performance during the 6-min walking test [69] or the 3-min step test [107]. Overall, little evidence is available on the effects of mixed programs, so further studies are needed that use clearly defined exercise programs and high-quality CRF measurements.
In summary, in patients with severe mental illness aerobic exercise, especially endurance training, has shown beneficial effects on global functioning, cognition, and negative and depressive symptoms. It stimulates synaptic and brain plasticity and affects the volume of specific brain regions, with genetic risk (SZ-PRS) influencing the results. However, despite the growing body of literature, the type, duration, and frequency of exercise needed for beneficial effects in the long term have yet to be determined before aerobic exercise will be used widely in general practice [109]. Some recommendations for further studies can be given from the perspective of sports medicine:
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The American College of Sports Medicine recommends that adults engage in moderate-intensity cardiorespiratory exercise training for ≥ 30 min/day on ≥ 5 days/week for a total of ≥ 150 min/week, or vigorous-intensity cardiorespiratory exercise training for ≥ 20 min/day on ≥ 3 days/week for a total of ≥ 75 min/week [110].
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Further studies are needed to identify the most effective exercise interventions (type, duration, frequency).
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Because most studies were conducted over a relatively short intervention period of 3 to 4 months, were supervised and did not include a follow-up, future studies should focus on long-term adherence to exercise (e.g., by implementing motivational strategies supported by telemedicine and apps and by identifying and targeting typical barriers to exercise in this patient population).
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This patient group has a high prevalence of cardiovascular disease, so researchers should consider measuring the associated risk factors when performing exercise intervention studies.
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CRF should be comprehensively assessed in both clinical studies and clinical practice by direct measurements of maximal oxygen uptake.
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Exercise interventional studies in patients with BD need to be conducted because this patient group is underrepresented.
References
Wittchen HU, Jacobi F, Rehm J, Gustavsson A, Svensson M, Jonsson B, Olesen J, Allgulander C, Alonso J, Faravelli C, Fratiglioni L, Jennum P, Lieb R, Maercker A, van Os J, Preisig M, Salvador-Carulla L, Simon R, Steinhausen HC (2011) The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacol 21:655–679. https://doi.org/10.1016/j.euroneuro.2011.07.018
Collaborators GDaIIaP (2017) Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 390:1211–1259. https://doi.org/10.1016/s0140-6736(17)32154-2
Gustavsson A, Svensson M, Jacobi F, Allgulander C, Alonso J, Beghi E, Dodel R, Ekman M, Faravelli C, Fratiglioni L (2011) Cost of disorders of the brain in Europe 2010. Eur Neuropsychopharmacol 21:718–779
Collaborators GDaI (2020) Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet 396:1204–1222. https://doi.org/10.1016/s0140-6736(20)30925-9
Kessler RC, Angermeyer M, Anthony JC, De Graaf R, Demyttenaere K, Gasquet I, De Girolamo G, Gluzman S, Gureje O, Haro JM (2007) Lifetime prevalence and age-of-onset distributions of mental disorders in the World Health Organization’s World Mental Health Survey Initiative. World Psychiatry 6:168
Kahn RS, Keefe RS (2013) Schizophrenia is a cognitive illness: time for a change in focus. JAMA Psychiat 70:1107–1112
Schennach R, Riedel M, Obermeier M, Spellmann I, Musil R, Jäger M, Schmauss M, Laux G, Pfeiffer H, Naber D (2015) What are residual symptoms in schizophrenia spectrum disorder? Clinical description and 1-year persistence within a naturalistic trial. Eur Arch Psychiatry Clin Neurosci 265:107–116
Häfner H, der Heiden W (2003) Course and outcome of schizophrenia. schizophrenia. Blackwell Science, Oxford, pp 101–141
Hasan A, Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, Thibaut F, Möller H-J, Schizophrenia WTfoTGf (2013) World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 2: update 2012 on the long-term treatment of schizophrenia and management of antipsychotic-induced side effects. World J Biol Psychiatry 14:2–44
Lawrence D, Hancock KJ, Kisely S (2013) The gap in life expectancy from preventable physical illness in psychiatric patients in Western Australia: retrospective analysis of population based registers. BMJ 346:f2539. https://doi.org/10.1136/bmj.f2539
Laursen TM, Munk-Olsen T, Gasse C (2011) Chronic somatic comorbidity and excess mortality due to natural causes in persons with schizophrenia or bipolar affective disorder. PLoS ONE 6:e24597
Jia H, Zack MM, Gottesman II, Thompson WW (2018) Associations of smoking, physical inactivity, heavy drinking, and obesity with quality-adjusted life expectancy among US adults with depression. Value Health 21:364–371
Hällgren J, Ösby U, Westman J, Gissler M (2019) Mortality trends in external causes of death in people with mental health disorders in Sweden, 1987–2010. Scand J Public Health 47:121–126
Ringen PA, Engh JA, Birkenaes AB, Dieset I, Andreassen OA (2014) Increased mortality in schizophrenia due to cardiovascular disease—a non-systematic review of epidemiology, possible causes, and interventions. Front Psychiatry 5:137. https://doi.org/10.3389/fpsyt.2014.00137
Walker ER, McGee RE, Druss BG (2015) Mortality in mental disorders and global disease burden implications: a systematic review and meta-analysis. JAMA Psychiat 72:334–341. https://doi.org/10.1001/jamapsychiatry.2014.2502
Kessing LV, Vradi E, Andersen PK (2015) Life expectancy in bipolar disorder. Bipolar Disord 17:543–548
Laursen TM, Wahlbeck K, Hällgren J, Westman J, Ösby U, Alinaghizadeh H, Gissler M, Nordentoft M (2013) Life expectancy and death by diseases of the circulatory system in patients with bipolar disorder or schizophrenia in the Nordic countries. PLoS ONE 8:e67133
Laursen TM, Musliner KL, Benros ME, Vestergaard M, Munk-Olsen T (2016) Mortality and life expectancy in persons with severe unipolar depression. J Affect Disord 193:203–207
De Hert M, Detraux J, Vancampfort D (2018) The intriguing relationship between coronary heart disease and mental disorders. Dialogues Clin Neurosci 20:31–40
Schmitt A, Maurus I, Rossner MJ, Roh A, Lembeck M, von Wilmsdorff M, Takahashi S, Rauchmann B, Keeser D, Hasan A, Malchow B, Falkai P (2018) Effects of aerobic exercise on metabolic syndrome, cardiorespiratory fitness, and symptoms in schizophrenia include decreased mortality. Front Psychiatry 9:690. https://doi.org/10.3389/fpsyt.2018.00690
Firth J, Siddiqi N, Koyanagi A, Siskind D, Rosenbaum S, Galletly C, Allan S, Caneo C, Carney R, Carvalho AF (2019) The lancet psychiatry commission: a blueprint for protecting physical health in people with mental illness. Lancet Psychiatry 6:675–712
Ross R, Blair SN, Arena R, Church TS, Després J-P, Franklin BA, Haskell WL, Kaminsky LA, Levine BD, Lavie CJ (2016) Importance of assessing cardiorespiratory fitness in clinical practice: a case for fitness as a clinical vital sign: a scientific statement from the American Heart Association. Circulation 134:e653–e699
Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr (2005) Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Circulation 112:2735–2752
Alberti KGMM, Zimmet P, Shaw J (2006) Metabolic syndrome—a new world-wide definition. A consensus statement from the international diabetes federation. Diabet Med 23:469–480
Vancampfort D, Stubbs B, Mitchell AJ, De Hert M, Wampers M, Ward PB, Rosenbaum S, Correll CU (2015) Risk of metabolic syndrome and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder: a systematic review and meta-analysis. World Psychiatry 14:339–347. https://doi.org/10.1002/wps.20252
Schuch F, Vancampfort D, Firth J, Rosenbaum S, Ward P, Reichert T, Bagatini NC, Bgeginski R, Stubbs B (2017) Physical activity and sedentary behavior in people with major depressive disorder: a systematic review and meta-analysis. J Affect Disord 210:139–150
Vancampfort D, Probst M, Scheewe T, De Herdt A, Sweers K, Knapen J, van Winkel R, De Hert M (2013) Relationships between physical fitness, physical activity, smoking and metabolic and mental health parameters in people with schizophrenia. Psychiatry Res 207:25–32
Vancampfort D, De Hert M, Vansteenkiste M, De Herdt A, Scheewe TW, Soundy A, Stubbs B, Probst M (2013) The importance of self-determined motivation towards physical activity in patients with schizophrenia. Psychiatry Res 210:812–818
Keller-Varady K, Hasan A, Schneider-Axmann T, Hillmer-Vogel U, Adomssent B, Wobrock T, Schmitt A, Niklas A, Falkai P, Malchow B (2016) Endurance training in patients with schizophrenia and healthy controls: differences and similarities. Eur Arch Psychiatry Clin Neurosci 266:461–473. https://doi.org/10.1007/s00406-015-0651-8
Vancampfort D, Stubbs B, Sienaert P, Wyckaert S, De Hert M, Soundy A, Probst M (2016) A comparison of physical fitness in patients with bipolar disorder, schizophrenia and healthy controls. Disabil Rehabil 38:2047–2051
Vancampfort D, De Hert M, Sweers K, De Herdt A, Detraux J, Probst M (2013) Diabetes, physical activity participation and exercise capacity in patients with schizophrenia. Psychiatry Clin Neurosci 67:451–456
Vancampfort D, Firth J, Correll CU, Solmi M, Siskind D, De Hert M, Carney R, Koyanagi A, Carvalho AF, Gaughran F (2019) The impact of pharmacological and non-pharmacological interventions to improve physical health outcomes in people with schizophrenia: a meta-review of meta-analyses of randomized controlled trials. World Psychiatry 18:53–66
Romain AJ, Fankam C, Karelis AD, Letendre E, Mikolajczak G, Stip E, Abdel-Baki A (2019) Effects of high intensity interval training among overweight individuals with psychotic disorders: a randomized controlled trial. Schizophr Res 210:278–286
Hargreaves M, Spriet LL (2020) Skeletal muscle energy metabolism during exercise. Nat Metab 2:817–828
WHO (2010) Global recommendations on physical activity for health. World Health Organization
Chamari K, Padulo J (2015) ‘Aerobic’and ‘Anaerobic’terms used in exercise physiology: a critical terminology reflection. Sports Medicine-Open 1:1–4
Oertel-Knochel V, Mehler P, Thiel C, Steinbrecher K, Malchow B, Tesky V, Ademmer K, Prvulovic D, Banzer W, Zopf Y, Schmitt A, Hansel F (2014) Effects of aerobic exercise on cognitive performance and individual psychopathology in depressive and schizophrenia patients. Eur Arch Psychiatry Clin Neurosci 264:589–604. https://doi.org/10.1007/s00406-014-0485-9
Toups M, Carmody T, Greer T, Rethorst C, Grannemann B, Trivedi MH (2017) Exercise is an effective treatment for positive valence symptoms in major depression. J Affect Disord 209:188–194
Greer TL, Trombello JM, Rethorst CD, Carmody TJ, Jha MK, Liao A, Grannemann BD, Chambliss HO, Church TS, Trivedi MH (2016) Improvements in psychosocial functioning and health-related quality of life following exercise augmentation in patients with treatment response but nonremitted major depressive disorder: results from the TREAD study. Depress Anxiety 33:870–881
Rethorst CD, South CC, Rush AJ, Greer TL, Trivedi MH (2017) Prediction of treatment outcomes to exercise in patients with nonremitted major depressive disorder. Depress Anxiety 34:1116–1122
Carneiro LS, Fonseca AM, Vieira-Coelho MA, Mota MP, Vasconcelos-Raposo J (2015) Effects of structured exercise and pharmacotherapy vs. pharmacotherapy for adults with depressive symptoms: a randomized clinical trial. J Psychiatr Res 71:48–55
Doose M, Ziegenbein M, Hoos O, Reim D, Stengert W, Hoffer N, Vogel C, Ziert Y, Sieberer M (2015) Self-selected intensity exercise in the treatment of major depression: a pragmatic RCT. Int J Psychiatry Clin Pract 19:266–275. https://doi.org/10.3109/13651501.2015.1082599
Legrand F, Heuze JP (2007) Antidepressant effects associated with different exercise conditions in participants with depression: a pilot study. J Sport Exerc Psychol 29:348–364
Patten CA, Vickers KS, Lewis BA, Finnie SB, Wheeldon TJ, Decker PA, Stevens S, Hathaway JC, Reese MM, Seime RJ (2019) Feasibility trial of an unsupervised, facility-based exercise programme for depressed outpatients. Psychol Health Med 24:320–332
Martinsen EW, Hoffart A, Solberg Ø (1989) Comparing aerobic with nonaerobic forms of exercise in the treatment of clinical depression: a randomized trial. Compr Psychiatry 30:324–331
Seshadri A, Adaji A, Orth SS, Singh B, Clark MM, Frye MA, Fuller-Tyszkiewicz M, and McGillivray J (2020) Exercise, yoga, and tai chi for treatment of major depressive disorder in outpatient settings: a systematic review and meta-analysis. Prim Care Companion CNS disord 23
Danielsson L, Papoulias I, Petersson E-L, Carlsson J, Waern M (2014) Exercise or basic body awareness therapy as add-on treatment for major depression: a controlled study. J Affect Disord 168:98–106
Minghetti A, Faude O, Hanssen H, Zahner L, Gerber M, Donath L (2018) Sprint interval training (SIT) substantially reduces depressive symptoms in major depressive disorder (MDD): a randomized controlled trial. Psychiatry Res 265:292–297
Krogh J, Saltin B, Nordentoft M (2009) The DEMO trial: a randomized, parallel-group, observer-blinded clinical trial of strength versus aerobic versus relaxation training for patients with mild to moderate depression. J Clin Psychiatry 70:790–800
Choi KW, Chen CY, Stein MB, Klimentidis YC, Wang MJ, Koenen KC, Smoller JW (2019) Assessment of bidirectional relationships between physical activity and depression among adults: a 2-sample mendelian randomization study. JAMA Psychiat 76:399–408. https://doi.org/10.1001/jamapsychiatry.2018.4175
Papiol S, Schmitt A, Maurus I, Rossner MJ, Schulze TG, Falkai P (2021) Association between physical activity and schizophrenia: results of a 2-sample Mendelian randomization analysis. JAMA Psychiat 78:441–444. https://doi.org/10.1001/jamapsychiatry.2020.3946
Ashton MM, Mohebbi M, Turner A, Marx W, Berk M, Malhi GS, Ng CH, Cotton SM, Dodd S, Sarris J (2020) Physical activity as a predictor of clinical trial outcomes in bipolar depression: a subanalysis of a mitochondrial-enhancing nutraceutical randomized controlled trial. Can J Psychiatry 65:306–318
Dauwan M, Begemann MJ, Heringa SM, Sommer IE (2016) Exercise improves clinical symptoms, quality of life, global functioning, and depression in schizophrenia: a systematic review and meta-analysis. Schizophr Bull 42:588–599. https://doi.org/10.1093/schbul/sbv164
Firth J, Stubbs B, Rosenbaum S, Vancampfort D, Malchow B, Schuch F, Elliott R, Nuechterlein KH, Yung AR (2017) Aerobic exercise improves cognitive functioning in people with schizophrenia: a systematic review and meta-analysis. Schizophr Bull 43:546–556. https://doi.org/10.1093/schbul/sbw115
Sabe M, Kaiser S, Sentissi O (2019) Physical exercise for negative symptoms of schizophrenia: Systematic review of randomized controlled trials and meta-analysis. Gen Hosp Psychiatry 62:13–20. https://doi.org/10.1016/j.genhosppsych.2019.11.002
Firth J, Cotter J, Elliott R, French P, Yung AR (2015) A systematic review and meta-analysis of exercise interventions in schizophrenia patients. Psychol Med 45:1343–1361. https://doi.org/10.1017/s0033291714003110
Pajonk FG, Wobrock T, Gruber O, Scherk H, Berner D, Kaizl I, Kierer A, Muller S, Oest M, Meyer T, Backens M, Schneider-Axmann T, Thornton AE, Honer WG, Falkai P (2010) Hippocampal plasticity in response to exercise in schizophrenia. Arch Gen Psychiatry 67:133–143. https://doi.org/10.1001/archgenpsychiatry.2009.193
Malchow B, Keller K, Hasan A, Dorfler S, Schneider-Axmann T, Hillmer-Vogel U, Honer WG, Schulze TG, Niklas A, Wobrock T, Schmitt A, Falkai P (2015) Effects of endurance training combined with cognitive remediation on everyday functioning, symptoms, and cognition in multiepisode schizophrenia patients. Schizophr Bull 41:847–858. https://doi.org/10.1093/schbul/sbv020
Falkai P, Maurus I, Schmitt A, Malchow B, Schneider-Axmann T, Röll L, Papiol S, Wobrock T, Hasan A, Keeser D (2021) Improvement in daily functioning after aerobic exercise training in schizophrenia is sustained after exercise cessation. Eur Arch Psychiatry Clin Neurosci 271:1201–1203. https://doi.org/10.1007/s00406-021-01282-8
Hallgren M, Skott M, Ekblom Ö, Firth J, Schembri A, Forsell Y (2019) Exercise effects on cognitive functioning in young adults with first-episode psychosis: FitForLife. Psychol Med 49:431–439
Su CY, Wang PW, Lin YJ, Tang TC, Liu MF, Chen MD (2016) The effects of aerobic exercise on cognition in schizophrenia: a 3-month follow-up study. Psychiatry Res 244:394–402. https://doi.org/10.1016/j.psychres.2016.08.011
Shimada T, Ito S, Makabe A, Yamanushi A, Takenaka A, Kobayashi M (2019) Aerobic exercise and cognitive functioning in schizophrenia: a pilot randomized controlled trial. Psychiatry Res 282:112638
Curcic D, Stojmenovic T, Djukic-Dejanovic S, Dikic N, Vesic-Vukasinovic M, Radivojevic N, Andjelkovic M, Borovcanin M, Djokic G (2017) Positive impact of prescribed physical activity on symptoms of schizophrenia: randomized clinical trial. Psychiatr Danub 29:459–465
Scheewe TW, Backx FJ, Takken T, Jorg F, van Strater AC, Kroes AG, Kahn RS, Cahn W (2013) Exercise therapy improves mental and physical health in schizophrenia: a randomised controlled trial. Acta Psychiatr Scand 127:464–473. https://doi.org/10.1111/acps.12029
Vancampfort D, De Hert M, Knapen J, Wampers M, Demunter H, Deckx S, Maurissen K, Probst M (2011) State anxiety, psychological stress and positive well-being responses to yoga and aerobic exercise in people with schizophrenia: a pilot study. Disabil Rehabil 33:684–689
Vancampfort D, Stubbs B, Van Damme T, Smith L, Hallgren M, Schuch F, Deenik J, Rosenbaum S, Ashdown-Franks G, Mugisha J (2020) The efficacy of meditation-based mind-body interventions for mental disorders: a meta-review of 17 meta-analyses of randomized controlled trials. J Psychiatr Res 134:181–191
Kang R, Wu Y, Li Z, Jiang J, Gao Q, Yu Y, Gao K, Yan Y, He Y (2016) Effect of community-based social skills training and tai-chi exercise on outcomes in patients with chronic schizophrenia: a randomized, one-year study. Psychopathology 49:345–355
Ho RT, Fong TC, Wan AH, Au-Yeung FS, Wong CP, Ng WY, Cheung IK, Lo PH, Ng S, Chan CL (2016) A randomized controlled trial on the psychophysiological effects of physical exercise and Tai-chi in patients with chronic schizophrenia. Schizophr Res 171:42–49
Kaltsatou A, Kouidi E, Fountoulakis K, Sipka C, Theochari V, Kandylis D, Deligiannis A (2015) Effects of exercise training with traditional dancing on functional capacity and quality of life in patients with schizophrenia: a randomized controlled study. Clin Rehabil 29:882–891
Andrade e Silva B, Cassilhas RC, Attux C, Cordeiro Q, Gadelha AL, Telles BA, Bressan RA, Ferreira FN, Rodstein PH, Daltio CS (2015) A 20-week program of resistance or concurrent exercise improves symptoms of schizophrenia: results of a blind, randomized controlled trial. Rev Bras Psiquiatr 37:271–279
Maurus I, Mantel C, Keller-Varady K, Schmitt A, Lembeck M, Röh A, Papazova I, Falkai P, Schneider-Axmann T, Hasan A (2020) Resistance training in patients with schizophrenia: concept and proof of principle trial. J Psychiatr Res 120:72–82
Maurus I, Hasan A, Röh A, Takahashi S, Rauchmann BS, Keeser D, Malchow B, Schmitt A, Falkai P (2019) Neurobiological effects of aerobic exercise, with a focus on patients with schizophrenia. Eur Arch Psychiatry Clin Neurosci 269:1–17
Wittfeld K, Jochem C, Dörr M, Schminke U, Gläser S, Bahls M, Markus MRP, Felix SB, Leitzmann MF, Ewert R, Bülow R, Völzke H, Janowitz D, Baumeister SE, Grabe HJ (2020) Cardiorespiratory fitness and gray matter volume in the temporal, frontal, and cerebellar regions in the general population. Mayo Clin Proc 95:44–56. https://doi.org/10.1016/j.mayocp.2019.05.030
Firth J, Stubbs B, Vancampfort D, Schuch F, Lagopoulos J, Rosenbaum S, Ward PB (2018) Effect of aerobic exercise on hippocampal volume in humans: a systematic review and meta-analysis. Neuroimage 166:230–238. https://doi.org/10.1016/j.neuroimage.2017.11.007
Adriano F, Caltagirone C, Spalletta G (2012) Hippocampal volume reduction in first-episode and chronic schizophrenia: a review and meta-analysis. Neuroscientist 18:180–200
Wise T, Radua J, Via E, Cardoner N, Abe O, Adams TM, Amico F, Cheng Y, Cole J, Périco CdAM (2017) Common and distinct patterns of grey-matter volume alteration in major depression and bipolar disorder: evidence from voxel-based meta-analysis. Mol Psychiatry 22:1455–1463
Rosano C, Guralnik J, Pahor M, Glynn NW, Newman AB, Ibrahim TS, Erickson K, Cohen R, Shaaban CE, MacCloud RL (2017) Hippocampal response to a 24-month physical activity intervention in sedentary older adults. Am J Geriatr Psychiatry 25:209–217
Gotlib IH, Joormann J (2010) Cognition and depression: current status and future directions. Annu Rev Clin Psychol 6:285–312
Green MF (2016) Impact of cognitive and social cognitive impairment on functional outcomes in patients with schizophrenia. J Clin Psychiatry 77(Suppl 2):8–11. https://doi.org/10.4088/JCP.14074su1c.02
Papiol S, Popovic D, Keeser D, Hasan A, Schneider-Axmann T, Degenhardt F, Rossner MJ, Bickeböller H, Schmitt A, Falkai P (2017) Polygenic risk has an impact on the structural plasticity of hippocampal subfields during aerobic exercise combined with cognitive remediation in multi-episode schizophrenia. Transl Psychiatry 7:e1159
Papiol S, Keeser D, Hasan A, Schneider-Axmann T, Raabe F, Degenhardt F, Rossner MJ, Bickeböller H, Cantuti-Castelvetri L, Simons M (2019) Polygenic burden associated to oligodendrocyte precursor cells and radial glia influences the hippocampal volume changes induced by aerobic exercise in schizophrenia patients. Transl Psychiatry 9:1–8
Falkai P, Malchow B, Wetzestein K, Nowastowski V, Bernstein H-G, Steiner J, Schneider-Axmann T, Kraus T, Hasan A, Bogerts B (2016) Decreased oligodendrocyte and neuron number in anterior hippocampal areas and the entire hippocampus in schizophrenia: a stereological postmortem study. Schizophr Bull 42:S4–S12
Schmitt A, Simons M, Cantuti-Castelvetri L, Falkai P (2019) A new role for oligodendrocytes and myelination in schizophrenia and affective disorders? Springer
Krogh J, Rostrup E, Thomsen C, Elfving B, Videbech P, Nordentoft M (2014) The effect of exercise on hippocampal volume and neurotrophines in patients with major depression—a randomized clinical trial. J Affect Disord 165:24–30
Scheewe TW, van Haren NE, Sarkisyan G, Schnack HG, Brouwer RM, de Glint M, Pol HEH, Backx FJ, Kahn RS, Cahn W (2013) Exercise therapy, cardiorespiratory fitness and their effect on brain volumes: a randomised controlled trial in patients with schizophrenia and healthy controls. Eur Neuropsychopharmacol 23:675–685
Woodward M, Gicas K, Warburton D, White R, Rauscher A, Leonova O, Su W, Smith G, Thornton A, Vertinsky A (2018) Hippocampal volume and vasculature before and after exercise in treatment-resistant schizophrenia. Schizophr Res 202:158–165
Takahashi S, Keeser D, Rauchmann B-S, Schneider-Axmann T, Keller-Varady K, Maurus I, Dechent P, Wobrock T, Hasan A, Schmitt A (2020) Effect of aerobic exercise combined with cognitive remediation on cortical thickness and prediction of social adaptation in patients with schizophrenia. Schizophr Res 216:397–407
Malchow B, Keeser D, Keller K, Hasan A, Rauchmann BS, Kimura H, Schneider-Axmann T, Dechent P, Gruber O, Ertl-Wagner B, Honer WG, Hillmer-Vogel U, Schmitt A, Wobrock T, Niklas A, Falkai P (2016) Effects of endurance training on brain structures in chronic schizophrenia patients and healthy controls. Schizophr Res 173:182–191. https://doi.org/10.1016/j.schres.2015.01.005
Rauchmann BS, Ghaseminejad F, Keeser D, Keller-Varady K, Schneider-Axmann T, Takahashi S, Karali T, Helms G, Dechent P, Maurus I, Hasan A, Wobrock T, Ertl-Wagner B, Schmitt A, Malchow B, Falkai P (2019) The impact of endurance training and table soccer on brain metabolites in schizophrenia. Brain Imaging Behav. https://doi.org/10.1007/s11682-019-00198-1
Svatkova A, Mandl RC, Scheewe TW, Cahn W, Kahn RS, Hulshoff Pol HE (2015) Physical exercise keeps the brain connected: biking increases white matter integrity in patients with schizophrenia and healthy controls. Schizophr Bull 41:869–878. https://doi.org/10.1093/schbul/sbv033
Vancampfort D, Kimbowa S, Basangwa D, Smith L, Stubbs B, Van Damme T, De Hert M, Mugisha J (2019) Test-retest reliability, concurrent validity and correlates of the two-minute walk test in outpatients with psychosis. Psychiatry Res 282:112619
Kerling A, Tegtbur U, Gützlaff E, Kück M, Borchert L, Ates Z, von Bohlen A, Frieling H, Hüper K, Hartung D, Schweiger U, Kahl KG (2015) Effects of adjunctive exercise on physiological and psychological parameters in depression: a randomized pilot trial. J Affect Disord 177:1–6. https://doi.org/10.1016/j.jad.2015.01.006
Krogh J, Videbech P, Thomsen C, Gluud C, Nordentoft M (2012) DEMO-II trial. Aerobic exercise versus stretching exercise in patients with major depression—a randomised clinical trial. PLoS ONE 7:e48316. https://doi.org/10.1371/journal.pone.0048316
Oeland AM, Laessoe U, Olesen AV, Munk-Jørgensen P (2010) Impact of exercise on patients with depression and anxiety. Nord J Psychiatry 64:210–217. https://doi.org/10.3109/08039480903511373
Hoffman BM, Blumenthal JA, Babyak MA, Smith PJ, Rogers SD, Doraiswamy PM, Sherwood A (2008) Exercise fails to improve neurocognition in depressed middle-aged and older adults. Med Sci Sports Exerc 40:1344–1352. https://doi.org/10.1249/MSS.0b013e31816b877c
Blumenthal JA, Babyak MA, Moore KA, Craighead WE, Herman S, Khatri P, Waugh R, Napolitano MA, Forman LM, Appelbaum M, Doraiswamy PM, Krishnan KR (1999) Effects of exercise training on older patients with major depression. Arch Intern Med 159:2349–2356
Gujral S, Aizenstein H, Reynolds CF III, Butters MA, Grove G, Karp JF, Erickson KI (2019) Exercise for depression: a feasibility trial exploring neural mechanisms. Am J Geriatr Psychiatry 27:611–616
Gerber M, Minghetti A, Beck J, Zahner L, Donath L (2019) 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 113:58–64
Andersen E, Bang-Kittilsen G, Bigseth TT, Egeland J, Holmen TL, Martinsen EW, Stensrud T, Engh JA (2020) Effect of high-intensity interval training on cardiorespiratory fitness, physical activity and body composition in people with schizophrenia: a randomized controlled trial. BMC Psychiatry 20:425. https://doi.org/10.1186/s12888-020-02827-2
Brobakken MF, Nygård M, Güzey IC, Morken G, Reitan SK, Heggelund J, Wang E, Vedul-Kjelsaas E (2019) Aerobic interval training in standard treatment of out-patients with schizophrenia: a randomized controlled trial. Acta Psychiatr Scand 140:498–507. https://doi.org/10.1111/acps.13105
Massa N, Alrohaibani A, Mammino K, Bello M, Taylor N, Cuthbert B, Fargotstein M, Coulter MM, Boatright JH, Nocera J, Duncan E (2020) The effect of aerobic exercise on physical and cognitive outcomes in a small cohort of outpatients with schizophrenia. Brain Plast 5:161–174. https://doi.org/10.3233/bpl-200105
Korman N, Fox H, Skinner T, Dodd C, Suetani S, Chapman J, Parker S, Dark F, Collins C, Rosenbaum S, Siskind D (2020) Feasibility and acceptability of a student-led lifestyle (diet and exercise) intervention within a residential rehabilitation setting for people with severe mental illness, GO HEART (Group Occupation, Health, Exercise And Rehabilitation Treatment). Front Psychiatry 11:319. https://doi.org/10.3389/fpsyt.2020.00319
Scheewe TW, Jörg F, Takken T, Deenik J, Vancampfort D, Backx FJG, Cahn W (2019) Low physical activity and cardiorespiratory fitness in people with schizophrenia: a comparison with matched healthy controls and associations with mental and physical health. Front Psychiatry 10:87. https://doi.org/10.3389/fpsyt.2019.00087
Heggelund J, Nilsberg GE, Hoff J, Morken G, Helgerud J (2011) Effects of high aerobic intensity training in patients with schizophrenia: a controlled trial. Nord J Psychiatry 65:269–275. https://doi.org/10.3109/08039488.2011.560278
Kimhy D, Tay C, Vakhrusheva J, Beck-Felts K, Ospina LH, Ifrah C, Parvaz M, Gross JJ, Bartels MN (2021) Enhancement of aerobic fitness improves social functioning in individuals with schizophrenia. Eur Arch Psychiatry Clin Neurosci 271:367–376. https://doi.org/10.1007/s00406-020-01220-0
Scheewe TW, Takken T, Kahn RS, Cahn W, Backx FJ (2012) Effects of exercise therapy on cardiorespiratory fitness in patients with schizophrenia. Med Sci Sports Exerc 44:1834–1842. https://doi.org/10.1249/MSS.0b013e318258e120
Cheng SL, Sun HF, Yeh ML (2017) Effects of an 8-week aerobic dance program on health-related fitness in patients with schizophrenia. J Nurs Res 25:429–435. https://doi.org/10.1097/jnr.0000000000000200
Yoon S, Ryu JK, Kim CH, Chang JG, Lee HB, Kim DH, Roh D (2016) Preliminary effectiveness and sustainability of group aerobic exercise program in patients with schizophrenia. J Nerv Ment Dis 204:644–650. https://doi.org/10.1097/nmd.0000000000000534
Schmitt A, Reich-Erkelenz D, Hasan A, Falkai P (2019) Aerobic exercise in mental disorders: from basic mechanisms to treatment recommendations. Eur Arch Psychiatry Clin Neurosci 269:483–484. https://doi.org/10.1007/s00406-019-01037-6
Garber CE, Blissmer B, Deschenes MR, Franklin BA, Lamonte MJ, Lee IM, Nieman DC, Swain DP (2011) American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Med Sci Sports Exerc 43:1334–1359. https://doi.org/10.1249/MSS.0b013e318213fefb
Font RM, Sanmartín MIF, López LMM, Tabueña NO, Canet SO, Echevarría LSE, Jato MI, Múgjica BD, Tejón SG, and Cabrera LV (2015) The effectiveness of a program of physical activity and diet to modify cardiovascular risk factors in patients with severe mental illness (CAPiCOR study). Int Arch Med 8
Penninx BW, Rejeski WJ, Pandya J, Miller ME, Di Bari M, Applegate WB, Pahor M (2002) Exercise and depressive symptoms: a comparison of aerobic and resistance exercise effects on emotional and physical function in older persons with high and low depressive symptomatology. J Gerontol B Psychol Sci Soc Sci 57:P124–P132
Dubreucq J, Gabayet F, Ycart B, Faraldo M, Melis F, Lucas T, Arnaud B, Bacconnier M, Bakri M, and Cambier G (2020) Improving social function with real-world social-cognitive remediation in schizophrenia: results from the RemedRugby quasi-experimental trial. Eur Psychiatry 63
Larsen LQ, Schnor H, Tersbøl BP, Ebdrup BH, Nordsborg NB, Midtgaard J (2019) The impact of exercise training complementary to early intervention in patients with first-episode psychosis: a qualitative sub-study from a randomized controlled feasibility trial. BMC Psychiatry 19:1–12
Bhatia T, Mazumdar S, Wood J, He F, Gur RE, Gur RC, Nimgaonkar VL, Deshpande SN (2017) A randomised controlled trial of adjunctive yoga and adjunctive physical exercise training for cognitive dysfunction in schizophrenia. Acta Neuropsychiatrica 29:102–114
Duncan MJ, Smith M, Clarke ND, Eyre EL, Wright SL (2016) Dual task performance in older adults: examining visual discrimination performance whilst treadmill walking at preferred and non-preferred speeds. Behav Brain Res 302:100–103
Kimhy D, Vakhrusheva J, Bartels MN, Armstrong HF, Ballon JS, Khan S, Chang RW, Hansen MC, Ayanruoh L, Lister A (2015) The impact of aerobic exercise on brain-derived neurotrophic factor and neurocognition in individuals with schizophrenia: a single-blind, randomized clinical trial. Schizophr Bull 41:859–868
Loh SY, Abdullah A, Bakar AKA, Thambu M, Jaafar NRN (2016) Structured walking and chronic institutionalized schizophrenia inmates: a pilot RCT study on quality of life. Global J Health Sci 8:238
Vancampfort D, Probst M, Stubbs B, Soundy A, De Herdt A, De Hert M (2014) Metabolic syndrome and lung function in schizophrenia: a pilot study. Psychiatry Res 220:58–62
Methapatara W, Srisurapanont M (2011) Pedometer walking plus motivational interviewing program for Thai schizophrenic patients with obesity or overweight: a 12-week, randomized, controlled trial. Psychiatry Clin Neurosci 65:374–380. https://doi.org/10.1111/j.1440-1819.2011.02225.x
Acknowledgements
This research was funded by the grants Klinische Forschergruppe (KFO) 241 and PsyCourse (FA241/16–1) to P. Falkai from the Deutsche Forschungsgemeinschaft (DFG). Further funding was received from the German Federal Ministry of Education and Research (BMBF) through the research network on psychiatric diseases ESPRIT (grant number 01EE1407E) to P. Falkai, A. Hasan, A. Schmitt. The authors thank Jacquie Klesing, BMedSci (Hons), Board-certified Editor in the Life Sciences (ELS), for editing assistance with the manuscript; Ms. Klesing received compensation for her work from the LMU Munich, Germany.
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C.P. Rosenbeiger, I. Maurus, B. Malchow, L. Hattenkofer, P. Heim-Ohmayer, M. Halle, and M. Heitkamp report no conflicts of interest. A. Hasan has been invited to scientific meetings by Lundbeck, Janssen, and Pfizer, and he received paid speakerships from Janssen, Otsuka, and Lundbeck. He was member of Roche, Otsuka, Lundbeck, and Janssen advisory boards. A. Schmitt was an honorary speaker for TAD Pharma and Roche and a member of Roche advisory boards. P. Falkai has been an honorary speaker for AstraZeneca, Bristol Myers Squibb, Lilly, Essex, GE Healthcare, GlaxoSmithKline, Janssen Cilag, Lundbeck, Otsuka, Pfizer, Servier, and Takeda and has been a member of the advisory boards of Janssen-Cilag, AstraZeneca, Lilly, and Lundbeck.
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Falkai, P., Schmitt, A., Rosenbeiger, C.P. et al. Aerobic exercise in severe mental illness: requirements from the perspective of sports medicine. Eur Arch Psychiatry Clin Neurosci 272, 643–677 (2022). https://doi.org/10.1007/s00406-021-01360-x
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DOI: https://doi.org/10.1007/s00406-021-01360-x