Psychological Responses to Acute Exercise in Patients With Stress-induced Exhaustion Disorder: a Cross-over Randomized Trial

Psychological Responses to Acute Exercise in Patients With Stress-induced Exhaustion Disorder: a Cross-over Randomized Trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Psychological Responses to Acute Exercise in Patients With Stress-induced Exhaustion Disorder: a Cross-over Randomized Trial Jenny Kling, Robert Persson Asplund, Örjan Ekblom, Victoria Blom This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5217618/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 24 Jan, 2025 Read the published version in BMC Psychiatry → Version 1 posted 10 You are reading this latest preprint version Abstract Background Understanding acute psychological responses to physical exercise is important since they likely influence the initiation and maintenance of this behavior. Given its effectiveness in reducing symptoms in various psychological disorders, physical exercise should be further explored in Exhaustion Disorder (ED; ICD-10-SE: F43.8A), a condition characterized by persistent exhaustion following long-term psychosocial stress. Currently, no studies are available on the psychological effects of acute exercise in ED patients. Aims This study aims to (1) investigate the psychological responses to acute exercise in ED patients compared to healthy controls and (2) determine if these responses differ between low and moderate exercise intensities. Methods We conducted a two-armed cross-over trial in two groups: ED patients (n = 30) and healthy controls (n = 30). On two separate occasions, participants completed a 22-minute exercise at low or moderate intensity on a cycle ergometer, in randomized order. The main outcome was perceived fatigue, and secondary outcomes were feelings of energy, anxiety, stress, perceived exertion, and perceived psychological discomfort, all measured before, during, and up to 24 hours after exercise. Effects of the exercise conditions were assessed with repeated measures analysis of variance. Results ED patients reported higher exertion and psychological discomfort before and during exercise, higher fatigue, anxiety, and stress but lower energy throughout the trial compared to the controls. ED patients experienced more reduced fatigue and stress after both intensities (p < 0.05), and a more elevated energy after moderate-intensity exercise compared to controls (p < 0.05). No interactions between groups were found for anxiety over time. No differences were observed between pre-exercise and 6 hours or 24 hours post-exercise in any variables. The only intensity effect (p < 0.05) in the ED patients was a more pronounced energy decline 30 minutes after moderate-intensity exercise. Conclusions A 22-minute exercise was perceived as more strenuous by patients with exhaustion disorder and generated greater improvements in feelings of fatigue, energy, and stress compared to healthy individuals, without delayed negative changes. These findings can inform intervention design and guide clinical practice. Trial registration The study was retrospectively registered on 05/30/2024 at Clinical Trials.gov, with trial registration number 2022-04943-01. Exercise Acute Exhaustion disorder Stress Fatigue Energy Anxiety Exercise intensity Figures Figure 1 Figure 2 Figure 3 Background Consequences of chronic psychosocial stress have increasingly contributed to the global issue of mental ill health. Exhaustion disorder (ED) is the primary reason for long-term sick leave in Sweden for all psychiatric and somatic diseases [1]. ED has been recognized in the Swedish edition of the International Statistical Classification of Diseases since 2005 (SE-ICD-10, code F43.8A.) [2]. The diagnosis is characterized by persistent mental and physical exhaustion, and noticeably reduced energy, resulting from identifiable psychosocial stressors that have been present for at least six months, without sufficient recovery. ED shares several symptomatic features with burnout but differs by including preceding non-work-related stressors. Consequently, individuals with ED also score high on burnout [3]. Given that economic and societal costs associated with stress-related disorders, primarily from sick leave and productivity loss, have been estimated at approximately 187 billion USD in the Western World [4] it is imperative that research focuses on feasible and effective treatments [5]. A recent umbrella review showed that habitual exercise is effective in symptom reduction of depression, anxiety, and distress both across multiple populations [6] and specifically for patients with depression and different anxiety- and stress disorders. As ED shares symptoms with several of these conditions, it may be assumed that exercise may hold beneficial effects also for ED. However, the benefits of regular exercise for burnout [7] as well as ED [5] remain inconclusive. Studies made on ED patients and physical activity (PA) interventions have shown that added exercise to a regular treatment gave small [8] or no effects on symptom severity [9]. An important factor in designing feasible and effective treatments for ED that contain PA is the psychological effects of acute exercise, given the likely central role of immediate exercise effects on affect and emotion in motivating sustained PA [10]. Previous research has shown that a 30-minute aerobic exercise bout can reduce mental health symptoms post-exercise across several psychiatric conditions. In patients with depression, it significantly decreased depression symptoms, regardless of exercise intensity [11]. Similarly, for patients with generalized anxiety disorder (GAD), running at a vigorous intensity significantly reduced anxiety and elevated energy, compared to quiet rest [12]. Additionally, moderate-intensity exercise had acute anxiolytic and anti-panic effects compared to quiet rest in patients with panic disorder [13]. In contrast, a meta-analysis on acute exercise effects in people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) showed increased fatigue post-exercise, with larger elevations several hours post-exercise [14]. To our knowledge, no prior study has examined the psychological response to acute exercise in individuals with ED. Consequently, the present study aimed to examine the acute psychological response to exercise in patients with ED compared to a healthy control group. A second study aim was to compare these responses across two exercise intensities - low and moderate. The focus was to assess the exercise-related effects on the primary outcome fatigue, as well as the secondary outcomes energy, anxiety, stress, psychological discomfort, and perceived exertion, as these are central aspects of ED. Increased knowledge may support the development of feasible and effective treatment strategies for this burdened patient group, while also capturing potential short-term benefits for symptom management. Methods Study design and participants To examine the psychological response to acute exercise in individuals with ED compared to healthy individuals, we conducted a two-armed cross-over trial comparing low and moderate exercise intensities in two groups: individuals diagnosed with ED and a healthy control group. Based on power calculations for the primary outcome (fatigue), a sample size of 30 patients with ED and 30 control participants would provide a power of 95% with a two-sided .05 significance level and a medium effect size. Participants were recruited through advertisements via Facebook, Instagram, and LinkedIn. Interested individuals followed an online link to complete a screening questionnaire that contained measures of ED and burnout, along with questions on mental and general health. Karolinska Exhaustion Disorder Scale (KEDS) was developed for the assessment of ED symptoms [15], and the proposed cut-off of 19 for discriminating between healthy subjects and patients with ED was used. Those who appeared eligible were contacted via telephone and were invited to fill out a baseline questionnaire and come to the research lab for a familiarization visit. During this visit, all participants underwent the Mini International Neuropsychiatric Interview 6.0.0. (M.I.N.I.) [16] complemented by questions targeting stress-related disorders in line with ICD-11 criteria [17]. See Fig. 1 for information on participant flow. Inclusion criteria for all participants were: (1) age 35–55 years, (2) fluent in Swedish, and (3) no medical contraindication for participation in PA. Exclusion criteria for all participants were: (1) CFS/ME, (2) chronic pain disorder, (3) recent post-covid, (4) current suicide risk, (5) current drug use or addiction, (6) current or previous bipolar disorder, (7) current or previous psychosis disorder, (8) untreated hypothyroidism, (9) blood pressure > 200/110, or (10) medication with beta-blockers. For inclusion in the ED group, inclusion criteria were: (1) a confirmed diagnosis of ED obtained through regular healthcare, (2) current ED symptomology based on the questionnaires and the diagnostic interview, assessed by a licensed psychologist experienced in working with the patient group, (3) an ED diagnosis not older than 18 months, and (4) not in the acute phase of ED. The control group was required to have self-reported good health as well as none of the specific ED criteria. All participants received written information about the study, were given an opportunity to ask questions, and provided informed consent before inclusion. The study was approved by the Swedish Ethical Review Authority (Approval Nr. 2022-04943-01). Participants were compensated with 1500 SEK upon completion for expenses related to participation, such as travel costs, leave of absence, etc. The study was retrospectively registered on 05/30/2024 at Clinical Trials.gov, with trial registration number 2022-04943-01. Baseline measures Before the familiarization visit, each participant completed an online questionnaire with sociodemographic and general health information, which was used for comparisons between the two groups. The following questionnaires were included: Saltin-Grimby Physical Activity Level Scale (SGPALS) [18], Karolinska Exhaustion Disorder Scale (KEDS) [15], a short version of the Shirom-Melamed Burnout Questionnaire/Measure (SMBM-12) [19], the trait subscale of The State-Trait Anxiety Inventory (STAI-Y2) [20], Patient Health Questionnaire (PHQ-9) [21], and Pittsburgh Sleep Quality Index (PSQI) [22]. Procedure The data collection took place from February 2022 to January 2023 in a laboratory setting at The Swedish School of Sport and Health Sciences (GIH) across three separate days. We provided transportation to GIH by taxi to minimize variations in PA before the test. The first visit served both to familiarize participants with the setting and the research team and to conduct pre-randomization assessments. This included the structured clinical interview previously described, plus measures of blood pressure and body mass. Blood pressure was measured using Digital Blood Pressure Monitor HEM-907 (OMRON, Kyoto, Japan) in a sitting position after at least 20 minutes of seated rest. Further, a submaximal cardiorespiratory fitness (CRF) test, performed on a calibrated mechanically braked cycle ergometer (Model 828E, Monark, Varberg, Sweden), to estimate maximal aerobic capacity (V̇O 2 max) [23]. Before this fitness test, participants were verbally informed about the procedures and introduced to Borg’s 6–20 rating of perceived exertion (RPE) scale [24] and Tanner’s Subjective Units of Distress (SUDS) scale [25] using visual analog scales (VAS). The fitness test began after individual adjustments of the cycle’s seat and handlebars and continued for approximately 8 minutes. The cycling work rate for the first level was set to 32 Watts work rate for 4 minutes, then increased to a personalized higher work rate for approximately 4 minutes. The personalized higher work rate aimed at corresponding to a perceived exertion of 13–16 (somewhat hard to hard) using RPE. The pedal frequency was maintained at 60 RPM throughout the test. V̇O 2 max was estimated using heart rate data collected during the test via an H10 heart rate sensor and Vantage M2 monitor (Polar, Kempele, Finland). The estimated V̇O 2 max was used to determine the intensity level for each participant in the subsequent trial conditions. The familiarization visit lasted approximately 90 minutes, and each of the two experimental visits lasted for about 120 minutes. Study outcomes To assess the effects of exercise on subjective transient feelings of fatigue, energy, anxiety, and stress, the following measures were included at the five time points immediately before, immediately after, 30 minutes after, 6 hours after, and 24 hours after the exercise bout: Fatigue and energy Previous research shows acute exercise effects on energy and fatigue [26], which are also core symptom areas in ED (ICD-10-SE). Feelings of energy and fatigue were measured with the vigor and fatigue subscales of Profile of Mood States (POMS), which assesses short-term affective states. Respondents are instructed to rate how they feel “right now” [27] and a total score on each subscale is calculated. The subscales range from 0 to 28 (fatigue) and 0 to 32 (energy), with higher values indicating higher levels of fatigue and energy respectively. An evaluation has supported its use in experimental settings to measure short-term intensity of energy and fatigue [28]. Anxiety There is support for acute exercise effects on anxiety [10], which is also commonly reported among ED patients [29]. State anxiety was measured using the 20-item state subscale of The State-Trait Anxiety Inventory (STAI-Y1) [20]. Respondents rate how they feel “right now” on a 4-point Likert Scale. A global score of state anxiety is calculated, ranging from 20–80, with higher scores corresponding to higher levels of state anxiety. STAI-Y1 has been extensively used in previous studies of acute exercise [30] and there is support for the STAI-Y1 being sensitive to change in response to acute aerobic exercise [12]. Stress Since ED patients report increased sensitivity to stress [29] and physical activity is a stressor, we included a measure of subjective short-term stress. The Single Item Stress Question (SISQ) [31] was adapted by the researchers performing the study to measure stress “right now” instead of “these days”. Respondents rated their stress level on a 5-point Likert scale, ranging from 1 to 5, with higher ratings corresponding to higher stress. The following measures were included at four time points: one immediately before the exercise, and three time points during the exercise: Perceived Exertion Borg’s 6–20 rating of perceived exertion (RPE) [24] scale was used to assess exertion during exercise. It is a single-item scale ranging from 6 (not strenuous at all) to 20 (maximally strenuous). Psychological discomfort Subjective Units of Distress scale (SUDS) [25] was used to assess subjective psychological discomfort during exercise. Respondents were instructed to rate the level of psychological discomfort on a scale from 0 to 10, with higher values corresponding to more discomfort. Experimental conditions The two experimental conditions, low and moderate exercise intensities, were conducted in a counterbalanced and randomly assigned cross-over design. The allocation sequence of experimental condition order was determined through individual randomization from a computer-generated random order. This was made before data collection started, by a researcher involved in the study (JK). After the familiarization assessment was completed, each participant enrolled in the study was assigned her/his order of experimental conditions consecutively and equally. Researchers involved in the data collection had access to the password-protected document and could prepare for each experimental day accordingly. The exercise intensities were standardized across participants using their estimated maximal aerobic capacity (V̇O 2 max), derived from the submaximal cardiorespiratory fitness tests. Intensities were based on classifications suggested by the American College of Sports Medicine [32] corresponding to 40 percent of V̇O 2 max for low, and 55 percent for moderate exercise intensity. The participants performed the two exercise conditions at a similar time of day, starting either 8:30 or 10:30 in the morning, with at least one week in between sessions. Blinding for condition or group was not practically possible, hence, a detailed script for the researcher was integrated into the test protocol to maintain standardization and thereby internal validity. After receiving verbal instructions on the exercise bout, participants were asked to rate the level of perceived exertion (RPE) and feelings of psychological discomfort (SUDS) on visual analog scales (VAS), followed by individual adjustment of the seat and handlebars. Participants then performed the 22-minute exercise on a cycle ergometer (model 839E, Monark, Varberg, Sweden), equipped with an automatic resistant adjustment feature, allowing participants to work out at their preferred RPM throughout the test while maintaining the intended rate of work. The exercise started with a 6-minute warm-up phase, where the load was gradually increased from 1 minute on 32 Watt, to 2 minutes on 50 percent, and then 2 minutes on 75 percent of the individualized work rate, before returning to 32 Watt for the last minute. Then followed 15 minutes on either low or moderate exercise intensity, which ended with a 1-minute cool-down on 32 Watt. One of the researchers was present during the complete test to ensure correct intensity and length, and the conversation was kept to a minimum. The first post-exercise measurements were followed by approximately 25 minutes of quiet rest in a seated position in an armchair with access to pillows and a blanket. During this quiet rest period talking was kept at a minimum, and participants were not allowed to use electronic devices but could choose from resting or reading magazines provided alternatively bring reading material of their own. The participants were asked to rate their level of perceived exertion and psychological discomfort on visual analog scales during the exercise, at 5, 10, and 15 minutes on the 15-minute exercise at low or moderate intensity. They completed questionnaires to measure fatigue, energy, anxiety, and stress at five time points: immediately before, immediately after, 30 minutes, 6 hours, and 24 hours after exercise. The initial three of these questionnaires were conducted during the experimental visit at GIH using tablets, while the latter two were digitally completed via links received via email. This extended measurement approach was designed to capture the immediate, short-term, and delayed psychological responses to exercise. Statistical analyses Descriptive data from baseline measures were calculated for participant characteristics. Means and standard deviations were calculated for the primary and secondary study outcomes (fatigue, perceived exertion, psychological discomfort, energy, anxiety, stress) for each group for all time points in both conditions. Effects of the exercise conditions were assessed with repeated measures analysis of variance (RM-ANOVA) to determine the main effects of group (ED patients and controls), intensity (low and moderate), and time (four time points for perceived exertion and psychological discomfort (pre, 5, 10, and 15 minutes); five time points for fatigue, energy, anxiety, and stress (pre, post, 30 minutes post, 6 hours post and 24 hours post) and interaction effects for group x time, group x intensity, time x intensity, and group x time x intensity. One control participant was excluded from analyses on fatigue, stress, anxiety, and energy, and one ED participant was excluded from analyses on RPE and SUDS due to missing data. Significant interactions were followed up with paired comparisons, with Bonferroni corrections to reduce the Type 1-error risk. Effects sizes were calculated using generalized eta squared [33]. The level of significance (α) was set to 0.05 for all statistical tests. Assumption checks regarding sphericity, homogeneity of variances (Levene’s) as well as inspecting Q-Q-plots, were performed for all RM-ANOVAs. Mauchly’s Tests of Sphericity performed for all variables were all significant. When the Greenhouse-Geisser value was > .75, Huynh-Feldt correction was applied, and Greenhouse-Geisser correction was used for values < .75. There was overall an issue with skewness and homogeneity of variances for the variables fatigue, anxiety, stress, and psychological discomfort. After natural logarithm (ln) transformation of the variables anxiety and psychological discomfort, skewness was reduced and none (anxiety) or few (psychological discomfort: 25%) of the Levene’s Test showed significant violations of the assumption of homogeneity of variance. Considering the issues with the assumptions of the RM-ANOVAs, significant results were verified with non-parametric tests. All data analyses were performed using Jamovi 2.3.28. Results Participant characteristics Thirty participants with ED (SE-ICD-10, code F43) and thirty age- and sex-matched healthy controls completed the study. Independent samples t-tests showed that ED patients and control participants differed significantly in several health variables (see Table 1 ), and that the groups were similar on demographic variables. Table 1 Baseline participant characteristics for the exhaustion disorder (ED) patients and the healthy controls ED ( n = 30) Control ( n = 30) Sex, women; n (%) 28 (93.3) 28 (93.3) Age, year; mean (SD) 46.3 (5.89) 45.8 (5.55) Highest education; n (%) Primary or upper-secondary 3 (10) 1 (3.33) Higher education 27 (90) 29 (96.67) Employment status; n (%) Full time 24 (80) 28 (93.3) Part-time 3 (10) 1 (3.33) Unemployed 3 (10) 0 (0) Studying 0 (0) 1 (3.33) Current sick leave; n (%) 23 (76.67) 0 (0) * Extend of sick leave; n (%) N/A 25% 1 (3.33) 0 (0) 50% 6 (20) 0 (0) 75% 5 (16.67) 0 (0) 100% 11 (36.67) 0 (0) Self-reported symptom duration, months; mean (SD) 7.05 (5.98) N/A Body Mass Index (BMI); mean (SD) 26.1 (5.39) 25.2 (3.98) Cardiorespiratory fitness (l/min); mean (SD) 2.41 (0.48) 2.85 (0.42) * Physical activity (SGPALS); n (%) * Almost completely inactive 0 (0) 0 (0) Moderately active 17 (56.67) 4 (13.33) * Highly active 11 (36.67) 19 (63.33) * Vigorously active 2 (6.67) 7 (23.33) Psychiatric diagnosis; n (%) * Depression 4 (13.33) 0 (0) * Anxiety disorders 5 (16.67) 0 (0) * Medication; n (%) * Antidepressants 15 (50) 3 (10) * Anxiolytics 2 (6.67) 0 (0) Sleeping medication 2 (6.67) 0 (0) Exhaustion disorder (KEDS); mean (SD) 32 (5.69) 5.6 (3.2) * Burnout (SMBM-12); mean (SD) 5.35 (0.95) 1.80 (0.61) * Trait anxiety (STAI-T); mean (SD) 53.2 (8.39) 36.1 (5.24) * Depression (PHQ-9); mean (SD) 11.9 (4.6) 1.63 (1.25) * Sleep quality (PSQI); mean (SD) 8.4 (2.75) 4.14 (1.51) * * indicates differences between groups at p < 0.05 Changes during exercise in perceived exertion and perceived psychological discomfort Perceived exertion Regarding perceived exertion (RPE) there was a significant interaction effect of time x intensity (η² G = 0.089), and significant main effects of group (η² G = 0.11), time (η² G = 0.82), and intensity (η² G = 0.23) (see Fig. 2 and Table 2 ). The ED group reported significantly higher RPE than the control group, showing that the exercise bouts were perceived as more strenuous for ED patients than for healthy controls. Post hoc tests on the significant time x intensity interaction effect showed that RPE significantly increased throughout all the consecutive time points except from 10 to 15 minutes during the tests with no differences between intensities. The participants reported significantly higher RPE at moderate than at low intensity. For more information on the post hoc tests, see Table S2 in Additional file 1. Table 2 Main and interaction effects of group (exhaustion disorder (ED) and control group), time (pre-, post-, 30 minutes post-, 6 hours post-, and 24 hours post-exercise), and intensity (low and moderate) RM-ANOVA Outcome Group (G) Time (T) Intensity (I) T x G I x G T x I T x I x G η² G ( p ) η² G ( p ) η² G ( p ) η² G ( p ) η² G ( p ) η² G ( p ) η² G ( p ) RPE 0.11 (< .001) 0.82 (< .001) 0.23 (< .001) 0.013 (0.08) 0.005 (0.13) 0.089 (< .001) 0.001 (0.42) lnSUDS 0.20 (< .001) 0.008 (0.11) 0.00 (0.81) 0.002 (0.59) 0.00 (0.71) 0.00 (0.95) 0.00 (0.70) Fatigue 0.49 (< .001) 0.024 (< .001) 0.00 (0.92) 0.025 (< .001) 0.001 (0.44) 0.005 (0.13) 0.008 (0.022) Energy 0.61 (< .001) 0.086 (< .001) 0.001 (0.15) 0.012 (0.014) 0.00 (0.61) 0.006 (0.013) 0.009 (< .001) lnAnxiety 0.47 (< .001) 0.089 (< .001) 0.00 (0.54) (0.005 (0.36) 0.001 (0.17) 0.002 (0.36) 0.002 (0.30) Stress 0.14 (< .001) 0.10 (< .001) 0.00 (0.62) 0.013 (0.034) 0.00 (0.62) 0.002 (0.53) 0.003 (0.49) RPE , Rating of perceived exertion; lnSUDS , subjective units of distress scale Psychological discomfort There was a significant main effect of group (η² G = 0.20) on psychological discomfort (see Fig. 2 and Table 2 ). The ED group experienced more discomfort than the control group. There were no main effects of time or intensity and no interaction effects regarding discomfort. Changes in fatigue, energy, anxiety, and stress after exercise Fatigue For fatigue, there was a significant interaction effect of time x intensity x group (η² G = 0.008). There were significant main effects of group (η² G = 0.49) and time (η² G = 0.024) but not of intensity (see Fig. 3 and Table 2 ). Post hoc tests on the significant time x intensity x group interaction effect (see Table S3, Additional file 1) revealed significant group differences on all time points in fatigue rating, i.e. the ED group reported higher levels of fatigue than the control group throughout all time points. The ED group had a reduction in fatigue immediately after exercise (post) compared to pre-exercise, which was sustained thirty minutes later (30 min post). This pattern was the same across the two intensities. The control group did not have the same direct exercise effect as the ED group. On the contrary, there were no differences between any measure points for the control group at low intensity, while at moderate intensity, the only significant difference between time points was higher fatigue levels 30 minutes post-exercise compared to immediately post-exercise. There were no significant differences between the pre-measure and the measures 6 hours or 24 hours post-exercise for either group. Energy There was a significant interaction effect of time x intensity x group on energy (η² G = 0.009), as well as significant main effects of group (η² G = 0.61) and time (η² G = 0.086) but not of intensity (see Fig. 3 and Table 2 ). Post hoc tests on the significant time x intensity x group interaction effect (see Table S4, Additional file 1) showed significant group differences on all time points in energy rating, i.e. the ED group reported lower energy than the control group throughout all corresponding time points. The ED group had a significant energy increase directly after exercises (post) on both intensities, while for the control group, this effect was significant only after the low-intensity exercise. Both groups had a significant decrease in energy 30 minutes after exercise compared to post-exercise at moderate, but not low, intensity. There were no significant differences in either group between the pre-measures and the measures 6 hours or 24 hours post-exercise. Anxiety There were significant main effects of group (η² G = 0.47) and time (η² G = 0.089), but not of intensity, on anxiety level (see Fig. 3 and Table 2 ). There were no interaction effects. The ED group reported significantly higher anxiety than the control group. Post hoc tests for the main effect of time (see Table S5, Additional file 1) revealed significantly lower anxiety directly after exercise (post) compared to pre-exercise. Anxiety declined even further 30 minutes after exercise, reflected in significantly lower anxiety levels 30 minutes post-exercise compared to post-exercise. There were no significant differences between the pre-measure and the measures 6 hours or 24 hours post-exercise. Stress There was a significant interaction effect of time x group on stress (η² G = 0.013), as well as significant main effects of group (η² G = 0.14) and time (η² G = 0.10) but not of intensity (see Fig. 3 and Table 2 ). Post hoc tests on the time x group interaction effect (see Table S6, Additional file 1) revealed that the ED group reported significantly higher stress levels than the control group on all corresponding time points except at 30 minutes and 6 hours after exercise. Additional group differences were that the ED group, but not the control group, experienced significantly lower stress levels immediately after exercise (post) compared to pre-exercise, which was maintained 30 minutes after exercise. There were no significant differences between the pre-measure and the measures 6 hours or 24 hours post, however, both groups displayed significantly higher stress levels 6 and 24 hours after exercise compared to directly after (post) exercise. Drop-out More eligible participants in the ED group (n = 16) dropped out than in the control group (n = 9) (see Fig. 1 ). The difference can be attributed to more ED patients declining before the study phase with the two experimental exercise visits. 118 out of the 120 exercise sessions were completed. Two participants in the ED group terminated the moderate-intensity exercise before completion. This occurred 10 minutes and 19 minutes respectively into the exercise session, both due to the participants perceiving the feeling of exertion as too high (18 and 20 RPE respectively). Data from the participant who stopped after 19 minutes has been included since almost the complete session was performed and after controlling for that it did not affect the analyses. Discussion To our knowledge, this study is the first to investigate the effects of acute exercise on patients with stress-induced exhaustion disorder (ED). Our primary goal was to examine the psychological responses to acute exercise in ED patients and compare them with those in healthy control participants. Our findings show that a short bout of aerobic exercise can alleviate symptoms experienced by ED patients, hence in line with previous research on the effects of exercise in managing symptoms involving patients with depression and anxiety disorders [11, 12, 13]. As expected, ED patients, compared to healthy controls, reported worse levels of fatigue, energy, anxiety, and stress in general, which reflects the common symptoms of ED. The exercise effects in ED patients differed from those in healthy controls in several ways. ED patients perceived the exercise as more strenuous but experienced greater reductions in fatigue and stress immediately after exercise, which was sustained also after a 30-minute rest post-exercise, along with more pronounced energy increases post-exercise. Additionally, we aimed to explore whether the response varied between low and moderate exercise intensities. We found that ED patients reacted with similar psychological responses to both intensities. During the exercise sessions, the ED patients experienced the activity as more strenuous than the healthy controls. This was expected given that mentally fatigued individuals rate exercise as more strenuous [34], and that marked physical weakness is a symptom of ED (ICD-10-SE). Hence, the higher self-reported exertion in ED patients may be attributed to central fatigue [35], an issue reported in studies on similar disorders [36, 37], rather than solely the physiological processes in exercise seen in overall healthy individuals. Central nervous system-related fatigue affects exercise performance together with peripheral fatigue also in healthy individuals but can be more pronounced in disorders such as ME/CFS and depression [36]. Previous studies in ME/CFS patients have shown higher perceived exertion ratings in relation to heart rate during exercise despite no defect in neuromuscular function, which has been attributed in part to central fatigue [37]. Interestingly, the elevation of exertion did not correspond with that of psychological discomfort. Although ED patients reported greater overall psychological discomfort, they did not experience a higher increase in discomfort compared to healthy controls. This is consistent with previous research in women with ED, showing higher overall SUDS ratings but no difference in psychological distress response compared to a control group when exposed to a mental stressor [38]. Hence, ED patients seem to respond similarly to mental and physical stressors in terms of psychological discomfort. As our study measured both perceived exertion and psychological discomfort during the exercise, the complexity of how exercise is experienced was highlighted. The notion that more strenuous physical activity does not necessarily correspond to increased psychological discomfort has support from previous research, which shows that affective displeasure does not correlate linearly with exercise intensity but instead plateaus at higher intensities above the ventilatory threshold [10], typically correlating to RPE ratings around 13 [39]. Despite the exercise being perceived as more strenuous by the ED group, it elicited more beneficial psychological effects post-exercise. Previous research made primarily on healthy individuals has found that acute exercise consistently increases energy [40]. However, results on fatigue are more heterogeneous, showing that fatigue reduction occurs when baseline fatigue is normal or high and when energy increase post-exercise is substantial [40]. The reductions in fatigue and increased energy in ED patients are hence consistent with these results. A study on college students with elevated fatigue [41] found similar reductions in fatigue after exercise at 50% of V̇O 2 max, resembling our study’s moderate-intensity exercise, but not at 75% of V̇O 2 max. The fatigue reductions in the ED group contrast with the elevated fatigue in ME/CFS patients post-exercise [42], a condition similar to ED characterized by persistent fatigue. This highlights differences between the two conditions. While ED patients experienced lowered fatigue post-exercise, controls did not, likely due to a floor effect, as their pre-exercise fatigue levels were already low (see Table S8, Additional file 1). In previous acute exercise studies showing fatigue-reducing effects, pre-exercise POMS fatigue scores averaged 6.42 [40], allowing for noticeable reductions. Conversely, the control group showed increased fatigue 30 minutes after moderate-intensity exercise. Typically, post-exercise fatigue increases occur when the baseline fatigue level is low [40], as in this study’s control group, but are otherwise also associated with high-intensity and longer-duration exercise [26]. Sustained reductions in fatigue have been observed in both healthy individuals [43] and those with substance abuse [44]. However, a difference from these studies is that participants generally experienced an immediate fatigue-reducing effect, which was not observed in the control group of this study. Both groups experienced elevated energy post-exercise, in line with previous research [40]. For ED patients, this effect was significant at both intensities, while for healthy controls, it was significant only at low intensity, though approaching significance at moderate intensity (p = .089). The lack of a pronounced energy increase from moderate-intensity exercise in the control group might contribute to the explanation of the delayed fatigue observed 30 minutes post-exercise, since energy has been shown to moderate changes in fatigue [40]. Besides a significantly more pronounced energy drop from post-exercise to 30 minutes after exercise at moderate intensity for both groups, and elevated fatigue in the control group 30 minutes after moderate-intensity exercise, the short exercise bouts did not produce significantly different psychological responses based on intensity. Previous research on intensity effects on affective states shows mixed results [10]. Many studies report no intensity effects, while others have found varied or negative effects on higher exercise intensities, particularly for energy and fatigue. However, a meta-analysis suggested greater anxiety-reducing effects at higher intensities due to the exposure, habituation, and reappraisal of bodily sensations similar to anxiety reactions (e.g., elevated heart rate, elevated breathing rate) [30]. Consequently, low-intensity exercise usually does not produce beneficial changes in fatigue, energy, and anxiety, as measured in this study. A more mechanistic study design could shed light on the mechanisms underlying these patterns in ED patients. Previous research generally shows small reductions in state anxiety [30], and an anxiety-reducing effect of the exercise was also observed in this study. The time x group interaction only approached significance (p = .077), making it uncertain how the two groups differed in their responses, but importantly, the ED group did not show increased anxiety after exercise (see Table S8, Additional file 1). Interestingly, anxiety levels decreased further during the 30-minute rest period following exercise, an effect not observed in previous studies, such as a meta-analysis including the same anxiety measure used here [30], or a recent study on depression patients that included a post-exercise rest period [45]. A partial explanation could be that the rest period was particularly valued by the ED patients due to their symptoms of exhaustion. Although not a part of the data collection protocol, anecdotal data indicated that many ED patients viewed the mandatory rest as a welcome treat. Additionally, the self-selected component of the quiet rest, where participants could choose to rest, sleep, read provided magazines, or bring their own reading material, may have contributed to the rest being viewed as an overall positive experience. The stress response curve was similar to that of anxiety, indicating an overlap between the two constructs. A recent meta-analysis on stress reactivity to a mental stressor found no reliable changes in self-reported stress after acute exercise [46], hence again highlighting the need to study mechanisms underlying responses. We believe that the measures 6 and 24 hours after exercise were important, as clinical observations suggest that concerns about delayed post-exercise fatigue and reduced energy often discourage PA in individuals with ED. Recent qualitative research [29] has supported this. Given that the psychological effects of acute exercise are transient, with positive activated affect like energy typically lasting up to 30 minutes [47], we did not expect improvements later in the day or the next morning. However, we considered potential delayed negative psychological effects, similar to those reported by CFS patients [14], especially since ED patients report such expectations [29]. Contrary to these assumptions, neither group showed increased fatigue, anxiety, stress, or decreased energy later in the day or the following morning compared to baseline, which is encouraging findings. It is important to note that this only concerns the short-term effects of single exercise sessions, and no conclusions can be drawn about the effects of repeated exercise. One factor potentially influencing the delayed ratings is the quiet rest post-exercise. It is possible that a rest period after exercise affected the ED group more, since lack of recovery, i.e. “psychophysiological unwinding after effort expenditure” [48] is central in the link between exposure to stressors and negative effects of stress. Hence, the delayed measurements show how exercise followed by 30 minutes of quiet rest affected the participants, not solely exercise. Fatigue, being a central clinical characteristic of ED (3, 29], can be defined as a “persistent sense of physical, emotional, and/or cognitive tiredness or exhaustion” [26] and implies a lack of ability to initialize and maintain mental and physical tasks that require effort and self-motivation. This has implications for the real-world transferability of the high compliance and low exercise sessions drop-out as participants had support in initiating the exercise, and researchers were present during sessions. Social support is an important factor for ED patients with less exercise experience in establishing an exercise routine [49]. Previous research shows that mental fatigue affects the choice of sedentary activities over physical activities, with the only exception being low intensities [50]. So although our results have positive short-term symptom management implications, the effort required to initiate and maintain short exercise sessions might be a considerable obstacle. This must be addressed in intervention design. There is limited data on how generalizable acute exercise studies are to long-term exercise effects. Thus, our study does not answer how ED patients would react psychologically to habitual exercise, warranting further studies. Acute exercise effects can however increase the chance of continuous exercise adherence, with previous research showing that lower levels of fatigue post-exercise correlate with more frequent exercise months later [51]. The beneficial effects of single exercise sessions observed here might thus potentially increase compliance with exercise in ED patients, by enhancing external motivation and limiting negative expectations of exercise consequences. Potential limitations One factor not manipulated in the study was the duration of exercise, which is another aspect influencing the psychological response to exercise. A meta-study on acute exercise effects on fatigue and energy [26] found that while exercise consistently increases feelings of energy, fatigue increases with longer duration, specifically beyond 20 minutes. However, a study comparing various combinations of durations of acute exercise (5–60 minutes) and subsequent rest periods showed no difference in fatigue ratings [43]. The exercise bouts in that study produced mean RPE ratings between 9.7 and 11.9, hence comparable to the low-intensity exercise in our study (see Table S7, Additional file 1). But considering that fatigue is central to ED, it might be that longer durations of exercise beyond 20 minutes affect this group more than many other populations. This highlights that the combination of intensity and duration affects the psychological response and must be considered jointly. Estimation of aerobic capacity was performed using an indirect method. As such, it contains errors larger than those related to direct or maximal test methods. However, maximal tests were deemed unsuitable for the ED group and any comparison to the controls could have been attributed to differences in ability to reach maximal effort. Nonetheless, the errors related to the submaximal, indirect test may have resulted in over- or underestimations, potentially causing participants in both groups to work at a higher or lower work rate than the intended 40% and 55%. We regard this as a random error that increases the variance and potentially results in an underestimation of real changes or differences, but not creating systematic group or time differences. Concerning blood pressure, we have no record on which arm it was measured, so there may have been variations. Since these measures were used solely for exclusion purposes and no participant was approaching the exclusion limit, we consider this a minor limitation. Another limitation regarding internal validity is that some participants may have slept during the resting period after the exercise bouts, which was not systematically registered. We did not include a measure of positive affect during exercise, which could have given a more comprehensive understanding of the psychological response [10]. Future studies should address this. However, one strength of our study is the inclusion of some psychological measures during exercise, which is often overlooked in acute exercise research. Since psychological responses are dynamic and not linear, this, combined with delayed measurements, provides a more complete picture of the psychological response to exercise in ED patients. The sample consisted primarily of women, with two men in each group. This limits the generalizability of the results to men. Gender differences in psychological responses to acute exercise are understudied, but one study [52] on young adults found such differences, with women showing greater improvements than men in fatigue and energy after 30 minutes of vigorous aerobic exercise. Generally, those with worse baseline values for variables such as anxiety [30], and energy level [47] experience significant beneficial effects of the exercise. Since women reported higher baseline problems with these variables, the observed differences might be due to the larger potential for benefits, rather than to gender differences. Experimental studies in a laboratory environment always have the issue of generalizability or external validity. Factors that could have contributed to negative experiences during the exercise (e.g. level of exertion and psychological discomfort) include that the exercise took place in a windowless room without distractions such as music or scenery. Exercising outdoors vs. indoors has been proposed to elicit lower RPE, and listening to music also has been shown to have beneficial effects on RPE [53]. The presence of a researcher during exercise might have affected the participants. Non-systematic observations indicated that some ED patients felt nervous about exercising, especially at moderate intensity, but felt safer in the controlled situation with a researcher present. However, a strength of the study is the comparison of the ED patients to a healthy control group, which allowed reliable conclusions about the psychological response to exercise specific to ED patients. This makes it easier to adjust the exercise recommendations existing for a healthy population. Additionally, the counterbalancing of exercise session order based on intensity enhances the reliability of conclusions about intensity effects, avoiding potential novelty effects on psychological discomfort, stress, and anxiety. Lastly, we had concerns that only ED patients with low symptom levels and limited impairment in important areas of functioning would participate in the study. This was however not substantiated, as demonstrated in the baseline exhaustion ratings and sickness absence (see Table 1 ). The large interest shown by individuals with an ED diagnosis in participating in the study indicates a large interest among them in exercise as an intervention. Further research This study aimed to shed some initial light on how acute exercise affects patients with ED, but several questions remain unanswered. Future studies could include exercise with different durations and higher exercise intensities, as well as explore the influence of different durations of rest post-exercise. The focus was on psychological responses to acute exercise, without exploring underlying processes that govern these responses in ED patients. Studies with a mechanistic focus can contribute to understanding the processes that underlie the psychological changes during and after exercise in ED patients. Research with a focus on susceptibility profiles is also needed, enabling more tailored exercise programs for the different needs of different ED patients. Potential moderators could include symptom severity, exercise level, fitness level, and BMI. While this study focused on aerobic exercise, other types of training, such as strength training, could also have beneficial psychological effects, and warrant further research. Conclusions The results from this study, showing that exercise at both low and moderate intensity can have short-term symptom benefits for ED patients, without adverse delayed symptom effects, are promising. Given that ED patients often fail to reach WHO recommendations for physical activity [54] these beneficial acute effects can be guidance in designing interventions that enhance long-term exercise adherence [10]. Declarations Ethics approval and consent to participate All participants received written information about the study, were given an opportunity to ask questions, and provided informed consent prior to inclusion. The study was approved by the Swedish Ethical Review Authority (Approval Nr. 2022-04943-01) and was conducted in accordance with the ethical principles of the Declaration of Helsinki. Consent for publication Not applicable. Availability of data and materials The data that was analyzed or produced in this study is not openly accessible due to Swedish legislation (the Swedish Ethical Review Act: 2003:460) but the authors can provide access upon reasonable request. For such inquiries, please contact VB. Competing interests The authors declare that they have no competing interests. Funding This study was conducted as part of E-PABS; a center of excellence in physical activity, healthy brain functions, and sustainability, based at The Swedish School of Sport and Health Sciences. The work was supported by the Knowledge Foundation (Grant no GIH 2021/8). The study sponsor had no role in the study design, collection, analysis, or interpretation of data of the study. Further, they had no role in the writing of the report or decision to submit the paper for publication. Authors’ contributions VB and RPA developed the initial idea for the study. VB, JK, RPA, and ÖE contributed to the design of the study in its final form. Data collection was performed by JK, together with individuals named in section Acknowledgements. JK conducted the statistical analyses with substantial input from VB, RPA, and ÖE. JK wrote the manuscript, and all authors provided critical revisions and approved the final version of the manuscript for submission. Acknowledgments The authors extend their sincere gratitude to all participants who made this study possible. Special thanks also to Amanda Lönn, who assisted with administration and practical aspects of data collection as well as contributed valuable input on the study protocols. We also want to acknowledge Emma Forsén Mantilla, Erik von Campenhausen, and Marcus Colling Holmberg for their efforts during the data collection. References Försäkringskassan. Sjukfrånvaro i psykiatriska diagnoser - En registerstudie av Sveriges arbetande befolkning i åldern 20–69 år. Analys och prognos; 2020 p. 108. Report No.: Socialförsäkringsrapport 2020:8. Available from: https://www.forsakringskassan.se/download/18.7fc616c01814e179a9f329/1656660446139/sjukfranvaro-i-psykiatriska-diagnoser-socialforsakringsrapport-2020-8.pdf. Accessed 29 Aug 2024. Socialstyrelsen. 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Supplementary Files 241007.FAinED.SUPPLEMENTARYMATERIAL.docx Cite Share Download PDF Status: Published Journal Publication published 24 Jan, 2025 Read the published version in BMC Psychiatry → Version 1 posted Editorial decision: Revision requested 25 Nov, 2024 Reviews received at journal 24 Nov, 2024 Reviews received at journal 08 Nov, 2024 Reviewers agreed at journal 08 Nov, 2024 Reviewers agreed at journal 27 Oct, 2024 Reviewers invited by journal 25 Oct, 2024 Editor invited by journal 14 Oct, 2024 Editor assigned by journal 12 Oct, 2024 Submission checks completed at journal 12 Oct, 2024 First submitted to journal 07 Oct, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5217618","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":382145839,"identity":"55cd3814-4363-473b-a6b0-73b1f2baf24f","order_by":0,"name":"Jenny Kling","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6UlEQVRIiWNgGAWjYBACxgYwlSDDBmQ/YDA4QLwWHqAWZgOitEBBAg+QYJNgYCBCC3N777HHPAxpPHzS7dcqvxTcYZBvbyDgsJ5z6cY8DDk8bDJnym7LGDxjMDhDwCbGGTlm0jwMFTxsEjlptyUMDjMYSCQQ0DL/DUJLMUiL/PwHhGzhAWkBOkwi/RjjB6AWhhv4dQD9kmMmOccgDWQLszSDwWEegzMEHGbYfsZM4k1Fspz8jPSHH3/8OSwn336AgJYGBgYmHgMQk8eAGRg7PAScxcAgD3LcDzCT/QGUMQpGwSgYBaMAFQAA1Pg8hQ25jkMAAAAASUVORK5CYII=","orcid":"","institution":"Swedish School of Sport and Health Sciences","correspondingAuthor":true,"prefix":"","firstName":"Jenny","middleName":"","lastName":"Kling","suffix":""},{"id":382145844,"identity":"ecbd47d3-a8a0-4f9b-9bde-392524516df3","order_by":1,"name":"Robert Persson Asplund","email":"","orcid":"","institution":"Swedish School of Sport and Health Sciences","correspondingAuthor":false,"prefix":"","firstName":"Robert","middleName":"Persson","lastName":"Asplund","suffix":""},{"id":382145845,"identity":"01984764-8551-4e65-9bae-75ea4195833f","order_by":2,"name":"Örjan Ekblom","email":"","orcid":"","institution":"Swedish School of Sport and Health Sciences","correspondingAuthor":false,"prefix":"","firstName":"Örjan","middleName":"","lastName":"Ekblom","suffix":""},{"id":382145846,"identity":"83eea574-49a5-4201-9887-6cb6ab0bc725","order_by":3,"name":"Victoria Blom","email":"","orcid":"","institution":"Swedish School of Sport and Health Sciences","correspondingAuthor":false,"prefix":"","firstName":"Victoria","middleName":"","lastName":"Blom","suffix":""}],"badges":[],"createdAt":"2024-10-07 11:08:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5217618/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5217618/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12888-025-06484-1","type":"published","date":"2025-01-24T15:58:18+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":71805865,"identity":"4045e458-8c63-487d-bee3-36d2437a001b","added_by":"auto","created_at":"2024-12-18 17:32:06","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":337740,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart showing the inclusion/exclusion process. ED, exhaustion disorder; ME/CFS, myalgic encephalomyelitis/chronic fatigue syndrome; AD, adjustment disorder. Adverse reactions: one control participant experienced chest pain, and another groin pain, upon which the exercise was immediately terminated, further participation ceased, and the participants were followed up with appropriate action.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5217618/v1/111008b343feb4fbc22119db.png"},{"id":71805335,"identity":"3a463783-9d23-498e-a0e1-b4c343c70480","added_by":"auto","created_at":"2024-12-18 17:24:06","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":172614,"visible":true,"origin":"","legend":"\u003cp\u003eChange over time in perceived exertion (RPE) range 6-20 and ln-transformed psychological discomfort (lnSUDS) during exercise.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5217618/v1/901d2f4d33881796dd2c41fc.png"},{"id":71805336,"identity":"64233b9d-655f-4567-8471-45fff5dc3598","added_by":"auto","created_at":"2024-12-18 17:24:06","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":313559,"visible":true,"origin":"","legend":"\u003cp\u003eChanges over time in fatigue (POMS) range 0-28, energy (POMS) range 0-32, stress range 1-5, and ln-transformed anxiety (lnSTAI-Y1).\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-5217618/v1/ccac7ecc568b8ad4846d5648.png"},{"id":74858537,"identity":"908a483c-b50e-4d72-86f5-4e339598d91d","added_by":"auto","created_at":"2025-01-27 16:11:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1804639,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5217618/v1/fb66a886-1460-449a-ac0e-1e3c15896d3e.pdf"},{"id":71805332,"identity":"58e7a7c3-0422-43c1-8632-67b99b005ce2","added_by":"auto","created_at":"2024-12-18 17:24:06","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":77379,"visible":true,"origin":"","legend":"","description":"","filename":"241007.FAinED.SUPPLEMENTARYMATERIAL.docx","url":"https://assets-eu.researchsquare.com/files/rs-5217618/v1/9597cb3305a5e8dcc26fea8c.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003ePsychological Responses to Acute Exercise in Patients With Stress-induced Exhaustion Disorder: a Cross-over Randomized Trial\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eConsequences of chronic psychosocial stress have increasingly contributed to the global issue of mental ill health. Exhaustion disorder (ED) is the primary reason for long-term sick leave in Sweden for all psychiatric and somatic diseases [1]. ED has been recognized in the Swedish edition of the International Statistical Classification of Diseases since 2005 (SE-ICD-10, code F43.8A.) [2]. The diagnosis is characterized by persistent mental and physical exhaustion, and noticeably reduced energy, resulting from identifiable psychosocial stressors that have been present for at least six months, without sufficient recovery. ED shares several symptomatic features with burnout but differs by including preceding non-work-related stressors. Consequently, individuals with ED also score high on burnout [3]. Given that economic and societal costs associated with stress-related disorders, primarily from sick leave and productivity loss, have been estimated at approximately 187\u0026nbsp;billion USD in the Western World [4] it is imperative that research focuses on feasible and effective treatments [5].\u003c/p\u003e \u003cp\u003eA recent umbrella review showed that habitual exercise is effective in symptom reduction of depression, anxiety, and distress both across multiple populations [6] and specifically for patients with depression and different anxiety- and stress disorders. As ED shares symptoms with several of these conditions, it may be assumed that exercise may hold beneficial effects also for ED. However, the benefits of regular exercise for burnout [7] as well as ED [5] remain inconclusive. Studies made on ED patients and physical activity (PA) interventions have shown that added exercise to a regular treatment gave small [8] or no effects on symptom severity [9].\u003c/p\u003e \u003cp\u003eAn important factor in designing feasible and effective treatments for ED that contain PA is the psychological effects of acute exercise, given the likely central role of immediate exercise effects on affect and emotion in motivating sustained PA [10]. Previous research has shown that a 30-minute aerobic exercise bout can reduce mental health symptoms post-exercise across several psychiatric conditions. In patients with depression, it significantly decreased depression symptoms, regardless of exercise intensity [11]. Similarly, for patients with generalized anxiety disorder (GAD), running at a vigorous intensity significantly reduced anxiety and elevated energy, compared to quiet rest [12]. Additionally, moderate-intensity exercise had acute anxiolytic and anti-panic effects compared to quiet rest in patients with panic disorder [13]. In contrast, a meta-analysis on acute exercise effects in people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) showed increased fatigue post-exercise, with larger elevations several hours post-exercise [14].\u003c/p\u003e \u003cp\u003eTo our knowledge, no prior study has examined the psychological response to acute exercise in individuals with ED. Consequently, the present study aimed to examine the acute psychological response to exercise in patients with ED compared to a healthy control group. A second study aim was to compare these responses across two exercise intensities - low and moderate. The focus was to assess the exercise-related effects on the primary outcome fatigue, as well as the secondary outcomes energy, anxiety, stress, psychological discomfort, and perceived exertion, as these are central aspects of ED. Increased knowledge may support the development of feasible and effective treatment strategies for this burdened patient group, while also capturing potential short-term benefits for symptom management.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eStudy design and participants\u003c/p\u003e \u003cp\u003eTo examine the psychological response to acute exercise in individuals with ED compared to healthy individuals, we conducted a two-armed cross-over trial comparing low and moderate exercise intensities in two groups: individuals diagnosed with ED and a healthy control group. Based on power calculations for the primary outcome (fatigue), a sample size of 30 patients with ED and 30 control participants would provide a power of 95% with a two-sided .05 significance level and a medium effect size. Participants were recruited through advertisements via Facebook, Instagram, and LinkedIn. Interested individuals followed an online link to complete a screening questionnaire that contained measures of ED and burnout, along with questions on mental and general health. Karolinska Exhaustion Disorder Scale (KEDS) was developed for the assessment of ED symptoms [15], and the proposed cut-off of 19 for discriminating between healthy subjects and patients with ED was used. Those who appeared eligible were contacted via telephone and were invited to fill out a baseline questionnaire and come to the research lab for a familiarization visit. During this visit, all participants underwent the Mini International Neuropsychiatric Interview 6.0.0. (M.I.N.I.) [16] complemented by questions targeting stress-related disorders in line with ICD-11 criteria [17]. See Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e for information on participant flow.\u003c/p\u003e \u003cp\u003eInclusion criteria for all participants were: (1) age 35\u0026ndash;55 years, (2) fluent in Swedish, and (3) no medical contraindication for participation in PA. Exclusion criteria for all participants were: (1) CFS/ME, (2) chronic pain disorder, (3) recent post-covid, (4) current suicide risk, (5) current drug use or addiction, (6) current or previous bipolar disorder, (7) current or previous psychosis disorder, (8) untreated hypothyroidism, (9) blood pressure\u0026thinsp;\u0026gt;\u0026thinsp;200/110, or (10) medication with beta-blockers. For inclusion in the ED group, inclusion criteria were: (1) a confirmed diagnosis of ED obtained through regular healthcare, (2) current ED symptomology based on the questionnaires and the diagnostic interview, assessed by a licensed psychologist experienced in working with the patient group, (3) an ED diagnosis not older than 18 months, and (4) not in the acute phase of ED. The control group was required to have self-reported good health as well as none of the specific ED criteria.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e All participants received written information about the study, were given an opportunity to ask questions, and provided informed consent before inclusion. The study was approved by the Swedish Ethical Review Authority (Approval Nr. 2022-04943-01). Participants were compensated with 1500 SEK upon completion for expenses related to participation, such as travel costs, leave of absence, etc. The study was retrospectively registered on 05/30/2024 at Clinical Trials.gov, with trial registration number 2022-04943-01.\u003c/p\u003e \u003cp\u003eBaseline measures\u003c/p\u003e \u003cp\u003eBefore the familiarization visit, each participant completed an online questionnaire with sociodemographic and general health information, which was used for comparisons between the two groups. The following questionnaires were included: Saltin-Grimby Physical Activity Level Scale (SGPALS) [18], Karolinska Exhaustion Disorder Scale (KEDS) [15], a short version of the Shirom-Melamed Burnout Questionnaire/Measure (SMBM-12) [19], the trait subscale of The State-Trait Anxiety Inventory (STAI-Y2) [20], Patient Health Questionnaire (PHQ-9) [21], and Pittsburgh Sleep Quality Index (PSQI) [22].\u003c/p\u003e \u003cp\u003eProcedure\u003c/p\u003e \u003cp\u003eThe data collection took place from February 2022 to January 2023 in a laboratory setting at The Swedish School of Sport and Health Sciences (GIH) across three separate days. We provided transportation to GIH by taxi to minimize variations in PA before the test. The first visit served both to familiarize participants with the setting and the research team and to conduct pre-randomization assessments. This included the structured clinical interview previously described, plus measures of blood pressure and body mass. Blood pressure was measured using Digital Blood Pressure Monitor HEM-907 (OMRON, Kyoto, Japan) in a sitting position after at least 20 minutes of seated rest. Further, a submaximal cardiorespiratory fitness (CRF) test, performed on a calibrated mechanically braked cycle ergometer (Model 828E, Monark, Varberg, Sweden), to estimate maximal aerobic capacity (V̇O\u003csub\u003e2\u003c/sub\u003e max) [23]. Before this fitness test, participants were verbally informed about the procedures and introduced to Borg\u0026rsquo;s 6\u0026ndash;20 rating of perceived exertion (RPE) scale [24] and Tanner\u0026rsquo;s Subjective Units of Distress (SUDS) scale [25] using visual analog scales (VAS). The fitness test began after individual adjustments of the cycle\u0026rsquo;s seat and handlebars and continued for approximately 8 minutes. The cycling work rate for the first level was set to 32 Watts work rate for 4 minutes, then increased to a personalized higher work rate for approximately 4 minutes. The personalized higher work rate aimed at corresponding to a perceived exertion of 13\u0026ndash;16 (somewhat hard to hard) using RPE. The pedal frequency was maintained at 60 RPM throughout the test. V̇O\u003csub\u003e2\u003c/sub\u003e max was estimated using heart rate data collected during the test via an H10 heart rate sensor and Vantage M2 monitor (Polar, Kempele, Finland). The estimated V̇O\u003csub\u003e2\u003c/sub\u003e max was used to determine the intensity level for each participant in the subsequent trial conditions. The familiarization visit lasted approximately 90 minutes, and each of the two experimental visits lasted for about 120 minutes.\u003c/p\u003e \u003cp\u003eStudy outcomes\u003c/p\u003e \u003cp\u003eTo assess the effects of exercise on subjective transient feelings of fatigue, energy, anxiety, and stress, the following measures were included at the five time points immediately before, immediately after, 30 minutes after, 6 hours after, and 24 hours after the exercise bout:\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eFatigue and energy\u003c/h2\u003e \u003cp\u003ePrevious research shows acute exercise effects on energy and fatigue [26], which are also core symptom areas in ED (ICD-10-SE). Feelings of energy and fatigue were measured with the vigor and fatigue subscales of Profile of Mood States (POMS), which assesses short-term affective states. Respondents are instructed to rate how they feel \u0026ldquo;right now\u0026rdquo; [27] and a total score on each subscale is calculated. The subscales range from 0 to 28 (fatigue) and 0 to 32 (energy), with higher values indicating higher levels of fatigue and energy respectively. An evaluation has supported its use in experimental settings to measure short-term intensity of energy and fatigue [28].\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eAnxiety\u003c/h3\u003e\n\u003cp\u003eThere is support for acute exercise effects on anxiety [10], which is also commonly reported among ED patients [29]. State anxiety was measured using the 20-item state subscale of The State-Trait Anxiety Inventory (STAI-Y1) [20]. Respondents rate how they feel \u0026ldquo;right now\u0026rdquo; on a 4-point Likert Scale. A global score of state anxiety is calculated, ranging from 20\u0026ndash;80, with higher scores corresponding to higher levels of state anxiety. STAI-Y1 has been extensively used in previous studies of acute exercise [30] and there is support for the STAI-Y1 being sensitive to change in response to acute aerobic exercise [12].\u003c/p\u003e\n\u003ch3\u003eStress\u003c/h3\u003e\n\u003cp\u003eSince ED patients report increased sensitivity to stress [29] and physical activity is a stressor, we included a measure of subjective short-term stress. The Single Item Stress Question (SISQ) [31] was adapted by the researchers performing the study to measure stress \u0026ldquo;right now\u0026rdquo; instead of \u0026ldquo;these days\u0026rdquo;. Respondents rated their stress level on a 5-point Likert scale, ranging from 1 to 5, with higher ratings corresponding to higher stress.\u003c/p\u003e \u003cp\u003eThe following measures were included at four time points: one immediately before the exercise, and three time points during the exercise:\u003c/p\u003e\n\u003ch3\u003ePerceived Exertion\u003c/h3\u003e\n\u003cp\u003eBorg\u0026rsquo;s 6\u0026ndash;20 rating of perceived exertion (RPE) [24] scale was used to assess exertion during exercise. It is a single-item scale ranging from 6 (not strenuous at all) to 20 (maximally strenuous).\u003c/p\u003e\n\u003ch3\u003ePsychological discomfort\u003c/h3\u003e\n\u003cp\u003eSubjective Units of Distress scale (SUDS) [25] was used to assess subjective psychological discomfort during exercise. Respondents were instructed to rate the level of psychological discomfort on a scale from 0 to 10, with higher values corresponding to more discomfort.\u003c/p\u003e \u003cp\u003eExperimental conditions\u003c/p\u003e \u003cp\u003eThe two experimental conditions, low and moderate exercise intensities, were conducted in a counterbalanced and randomly assigned cross-over design. The allocation sequence of experimental condition order was determined through individual randomization from a computer-generated random order. This was made before data collection started, by a researcher involved in the study (JK). After the familiarization assessment was completed, each participant enrolled in the study was assigned her/his order of experimental conditions consecutively and equally. Researchers involved in the data collection had access to the password-protected document and could prepare for each experimental day accordingly. The exercise intensities were standardized across participants using their estimated maximal aerobic capacity (V̇O\u003csub\u003e2\u003c/sub\u003e max), derived from the submaximal cardiorespiratory fitness tests. Intensities were based on classifications suggested by the American College of Sports Medicine [32] corresponding to 40 percent of V̇O\u003csub\u003e2\u003c/sub\u003e max for low, and 55 percent for moderate exercise intensity.\u003c/p\u003e \u003cp\u003eThe participants performed the two exercise conditions at a similar time of day, starting either 8:30 or 10:30 in the morning, with at least one week in between sessions. Blinding for condition or group was not practically possible, hence, a detailed script for the researcher was integrated into the test protocol to maintain standardization and thereby internal validity. After receiving verbal instructions on the exercise bout, participants were asked to rate the level of perceived exertion (RPE) and feelings of psychological discomfort (SUDS) on visual analog scales (VAS), followed by individual adjustment of the seat and handlebars. Participants then performed the 22-minute exercise on a cycle ergometer (model 839E, Monark, Varberg, Sweden), equipped with an automatic resistant adjustment feature, allowing participants to work out at their preferred RPM throughout the test while maintaining the intended rate of work. The exercise started with a 6-minute warm-up phase, where the load was gradually increased from 1 minute on 32 Watt, to 2 minutes on 50 percent, and then 2 minutes on 75 percent of the individualized work rate, before returning to 32 Watt for the last minute. Then followed 15 minutes on either low or moderate exercise intensity, which ended with a 1-minute cool-down on 32 Watt. One of the researchers was present during the complete test to ensure correct intensity and length, and the conversation was kept to a minimum. The first post-exercise measurements were followed by approximately 25 minutes of quiet rest in a seated position in an armchair with access to pillows and a blanket. During this quiet rest period talking was kept at a minimum, and participants were not allowed to use electronic devices but could choose from resting or reading magazines provided alternatively bring reading material of their own.\u003c/p\u003e \u003cp\u003eThe participants were asked to rate their level of perceived exertion and psychological discomfort on visual analog scales during the exercise, at 5, 10, and 15 minutes on the 15-minute exercise at low or moderate intensity. They completed questionnaires to measure fatigue, energy, anxiety, and stress at five time points: immediately before, immediately after, 30 minutes, 6 hours, and 24 hours after exercise. The initial three of these questionnaires were conducted during the experimental visit at GIH using tablets, while the latter two were digitally completed via links received via email. This extended measurement approach was designed to capture the immediate, short-term, and delayed psychological responses to exercise.\u003c/p\u003e \u003cp\u003eStatistical analyses\u003c/p\u003e \u003cp\u003eDescriptive data from baseline measures were calculated for participant characteristics. Means and standard deviations were calculated for the primary and secondary study outcomes (fatigue, perceived exertion, psychological discomfort, energy, anxiety, stress) for each group for all time points in both conditions. Effects of the exercise conditions were assessed with repeated measures analysis of variance (RM-ANOVA) to determine the main effects of group (ED patients and controls), intensity (low and moderate), and time (four time points for perceived exertion and psychological discomfort (pre, 5, 10, and 15 minutes); five time points for fatigue, energy, anxiety, and stress (pre, post, 30 minutes post, 6 hours post and 24 hours post) and interaction effects for group x time, group x intensity, time x intensity, and group x time x intensity. One control participant was excluded from analyses on fatigue, stress, anxiety, and energy, and one ED participant was excluded from analyses on RPE and SUDS due to missing data. Significant interactions were followed up with paired comparisons, with Bonferroni corrections to reduce the Type 1-error risk. Effects sizes were calculated using generalized eta squared [33]. The level of significance (α) was set to 0.05 for all statistical tests. Assumption checks regarding sphericity, homogeneity of variances (Levene\u0026rsquo;s) as well as inspecting Q-Q-plots, were performed for all RM-ANOVAs. Mauchly\u0026rsquo;s Tests of Sphericity performed for all variables were all significant. When the Greenhouse-Geisser value was \u0026gt;\u0026thinsp;.75, Huynh-Feldt correction was applied, and Greenhouse-Geisser correction was used for values\u0026thinsp;\u0026lt;\u0026thinsp;.75. There was overall an issue with skewness and homogeneity of variances for the variables fatigue, anxiety, stress, and psychological discomfort. After natural logarithm (ln) transformation of the variables anxiety and psychological discomfort, skewness was reduced and none (anxiety) or few (psychological discomfort: 25%) of the Levene\u0026rsquo;s Test showed significant violations of the assumption of homogeneity of variance. Considering the issues with the assumptions of the RM-ANOVAs, significant results were verified with non-parametric tests. All data analyses were performed using Jamovi 2.3.28.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eParticipant characteristics\u003c/p\u003e \u003cp\u003e Thirty participants with ED (SE-ICD-10, code F43) and thirty age- and sex-matched healthy controls completed the study. Independent samples t-tests showed that ED patients and control participants differed significantly in several health variables (see Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), and that the groups were similar on demographic variables.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline participant characteristics for the exhaustion disorder (ED) patients and the healthy controls\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eED (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex, women;\u003c/b\u003e \u003cb\u003en\u003c/b\u003e \u003cb\u003e(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (93.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (93.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge, year; mean (SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46.3 (5.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45.8 (5.55)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHighest education;\u003c/b\u003e \u003cb\u003en\u003c/b\u003e \u003cb\u003e(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary or upper-secondary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (3.33)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigher education\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (96.67)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEmployment status;\u003c/b\u003e \u003cb\u003en\u003c/b\u003e \u003cb\u003e(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFull time\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (93.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePart-time\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (3.33)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnemployed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStudying\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (3.33)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCurrent sick leave;\u003c/b\u003e \u003cb\u003en\u003c/b\u003e \u003cb\u003e(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e23 (76.67)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0 (0) *\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eExtend of sick leave;\u003c/b\u003e \u003cb\u003en\u003c/b\u003e \u003cb\u003e(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (3.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e75%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (16.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (36.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSelf-reported symptom duration, months; mean (SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.05 (5.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBody Mass Index (BMI); mean (SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.1 (5.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.2 (3.98)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCardiorespiratory fitness (l/min); mean (SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e2.41 (0.48)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e2.85 (0.42)\u0026nbsp;*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePhysical activity (SGPALS);\u003c/b\u003e \u003cb\u003en\u003c/b\u003e \u003cb\u003e(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlmost completely inactive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerately active\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e17 (56.67)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e4 (13.33)\u0026nbsp;*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHighly active\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e11 (36.67)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e19 (63.33)\u0026nbsp;*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVigorously active\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (23.33)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePsychiatric diagnosis;\u003c/b\u003e \u003cb\u003en\u003c/b\u003e \u003cb\u003e(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDepression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e4 (13.33)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0 (0)\u0026nbsp;*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnxiety disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e5 (16.67)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0 (0)\u0026nbsp;*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedication;\u003c/b\u003e \u003cb\u003en\u003c/b\u003e \u003cb\u003e(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntidepressants\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e15 (50)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e3 (10)\u0026nbsp;*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnxiolytics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSleeping medication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eExhaustion disorder (KEDS); mean (SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e32 (5.69)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e5.6 (3.2)\u0026nbsp;*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBurnout (SMBM-12); mean (SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e5.35 (0.95)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e1.80 (0.61)\u0026nbsp;*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTrait anxiety (STAI-T); mean (SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e53.2 (8.39)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e36.1 (5.24)\u0026nbsp;*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDepression (PHQ-9); mean (SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e11.9 (4.6)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e1.63 (1.25)\u0026nbsp;*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSleep quality (PSQI); mean (SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e8.4 (2.75)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e4.14 (1.51)\u0026nbsp;*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e\u003cb\u003e*\u003c/b\u003e indicates differences between groups at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eChanges during exercise in perceived exertion and perceived psychological discomfort\u003c/p\u003e\n\u003ch3\u003ePerceived exertion\u003c/h3\u003e\n\u003cp\u003eRegarding perceived exertion (RPE) there was a significant interaction effect of time x intensity (η\u0026sup2;\u003csub\u003eG\u003c/sub\u003e = 0.089), and significant main effects of group (η\u0026sup2;\u003csub\u003eG\u003c/sub\u003e = 0.11), time (η\u0026sup2;\u003csub\u003eG\u003c/sub\u003e = 0.82), and intensity (η\u0026sup2;\u003csub\u003eG\u003c/sub\u003e = 0.23) (see Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The ED group reported significantly higher RPE than the control group, showing that the exercise bouts were perceived as more strenuous for ED patients than for healthy controls. Post hoc tests on the significant time x intensity interaction effect showed that RPE significantly increased throughout all the consecutive time points except from 10 to 15 minutes during the tests with no differences between intensities. The participants reported significantly higher RPE at moderate than at low intensity. For more information on the post hoc tests, see Table S2 in Additional file 1.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMain and interaction effects of group (exhaustion disorder (ED) and control group), time (pre-, post-, 30 minutes post-, 6 hours post-, and 24 hours post-exercise), and intensity (low and moderate) RM-ANOVA\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGroup (G)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTime (T)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIntensity (I)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eT x G\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eI x G\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eT x I\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eT x I x G\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eη\u0026sup2;\u003csub\u003eG\u003c/sub\u003e (\u003cem\u003ep\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eη\u0026sup2;\u003csub\u003eG\u003c/sub\u003e (\u003cem\u003ep\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eη\u0026sup2;\u003csub\u003eG\u003c/sub\u003e (\u003cem\u003ep\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eη\u0026sup2;\u003csub\u003eG\u003c/sub\u003e (\u003cem\u003ep\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eη\u0026sup2;\u003csub\u003eG\u003c/sub\u003e (\u003cem\u003ep\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eη\u0026sup2;\u003csub\u003eG\u003c/sub\u003e (\u003cem\u003ep\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eη\u0026sup2;\u003csub\u003eG\u003c/sub\u003e (\u003cem\u003ep\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRPE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.11 (\u0026lt;\u0026thinsp;.001)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.82 (\u0026lt;\u0026thinsp;.001)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.23 (\u0026lt;\u0026thinsp;.001)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.013 (0.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.005 (0.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.089 (\u0026lt;\u0026thinsp;.001)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.001 (0.42)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003elnSUDS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.20 (\u0026lt;\u0026thinsp;.001)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.008 (0.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.00 (0.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.002 (0.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.00 (0.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.00 (0.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.00 (0.70)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFatigue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.49 (\u0026lt;\u0026thinsp;.001)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.024 (\u0026lt;\u0026thinsp;.001)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.00 (0.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.025 (\u0026lt;\u0026thinsp;.001)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.001 (0.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.005 (0.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.008 (0.022)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEnergy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.61 (\u0026lt;\u0026thinsp;.001)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.086 (\u0026lt;\u0026thinsp;.001)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001 (0.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.012 (0.014)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.00 (0.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.006 (0.013)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.009 (\u0026lt;\u0026thinsp;.001)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003elnAnxiety\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.47 (\u0026lt;\u0026thinsp;.001)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.089 (\u0026lt;\u0026thinsp;.001)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.00 (0.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(0.005 (0.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.001 (0.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.002 (0.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.002 (0.30)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStress\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.14 (\u0026lt;\u0026thinsp;.001)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.10 (\u0026lt;\u0026thinsp;.001)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.00 (0.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.013 (0.034)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.00 (0.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.002 (0.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.003 (0.49)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eRPE\u003c/em\u003e, Rating of perceived exertion; \u003cem\u003elnSUDS\u003c/em\u003e, subjective units of distress scale\u003c/p\u003e\n\u003ch3\u003ePsychological discomfort\u003c/h3\u003e\n\u003cp\u003eThere was a significant main effect of group (η\u0026sup2;\u003csub\u003eG\u003c/sub\u003e = 0.20) on psychological discomfort (see Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The ED group experienced more discomfort than the control group. There were no main effects of time or intensity and no interaction effects regarding discomfort.\u003c/p\u003e \u003cp\u003eChanges in fatigue, energy, anxiety, and stress after exercise\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eFatigue\u003c/h2\u003e \u003cp\u003eFor fatigue, there was a significant interaction effect of time x intensity x group (η\u0026sup2;\u003csub\u003eG\u003c/sub\u003e = 0.008). There were significant main effects of group (η\u0026sup2;\u003csub\u003eG\u003c/sub\u003e = 0.49) and time (η\u0026sup2;\u003csub\u003eG\u003c/sub\u003e = 0.024) but not of intensity (see Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Post hoc tests on the significant time x intensity x group interaction effect (see Table S3, Additional file 1) revealed significant group differences on all time points in fatigue rating, i.e. the ED group reported higher levels of fatigue than the control group throughout all time points. The ED group had a reduction in fatigue immediately after exercise (post) compared to pre-exercise, which was sustained thirty minutes later (30 min post). This pattern was the same across the two intensities. The control group did not have the same direct exercise effect as the ED group. On the contrary, there were no differences between any measure points for the control group at low intensity, while at moderate intensity, the only significant difference between time points was higher fatigue levels 30 minutes post-exercise compared to immediately post-exercise. There were no significant differences between the pre-measure and the measures 6 hours or 24 hours post-exercise for either group.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eEnergy\u003c/h2\u003e \u003cp\u003eThere was a significant interaction effect of time x intensity x group on energy (η\u0026sup2;\u003csub\u003eG\u003c/sub\u003e = 0.009), as well as significant main effects of group (η\u0026sup2;\u003csub\u003eG\u003c/sub\u003e = 0.61) and time (η\u0026sup2;\u003csub\u003eG\u003c/sub\u003e = 0.086) but not of intensity (see Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Post hoc tests on the significant time x intensity x group interaction effect (see Table S4, Additional file 1) showed significant group differences on all time points in energy rating, i.e. the ED group reported lower energy than the control group throughout all corresponding time points. The ED group had a significant energy increase directly after exercises (post) on both intensities, while for the control group, this effect was significant only after the low-intensity exercise. Both groups had a significant decrease in energy 30 minutes after exercise compared to post-exercise at moderate, but not low, intensity. There were no significant differences in either group between the pre-measures and the measures 6 hours or 24 hours post-exercise.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eAnxiety\u003c/h2\u003e \u003cp\u003eThere were significant main effects of group (η\u0026sup2;\u003csub\u003eG\u003c/sub\u003e = 0.47) and time (η\u0026sup2;\u003csub\u003eG\u003c/sub\u003e = 0.089), but not of intensity, on anxiety level (see Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). There were no interaction effects. The ED group reported significantly higher anxiety than the control group. Post hoc tests for the main effect of time (see Table S5, Additional file 1) revealed significantly lower anxiety directly after exercise (post) compared to pre-exercise. Anxiety declined even further 30 minutes after exercise, reflected in significantly lower anxiety levels 30 minutes post-exercise compared to post-exercise. There were no significant differences between the pre-measure and the measures 6 hours or 24 hours post-exercise.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eStress\u003c/h2\u003e \u003cp\u003eThere was a significant interaction effect of time x group on stress (η\u0026sup2;\u003csub\u003eG\u003c/sub\u003e = 0.013), as well as significant main effects of group (η\u0026sup2;\u003csub\u003eG\u003c/sub\u003e = 0.14) and time (η\u0026sup2;\u003csub\u003eG\u003c/sub\u003e = 0.10) but not of intensity (see Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Post hoc tests on the time x group interaction effect (see Table S6, Additional file 1) revealed that the ED group reported significantly higher stress levels than the control group on all corresponding time points except at 30 minutes and 6 hours after exercise. Additional group differences were that the ED group, but not the control group, experienced significantly lower stress levels immediately after exercise (post) compared to pre-exercise, which was maintained 30 minutes after exercise. There were no significant differences between the pre-measure and the measures 6 hours or 24 hours post, however, both groups displayed significantly higher stress levels 6 and 24 hours after exercise compared to directly after (post) exercise.\u003c/p\u003e \u003cp\u003eDrop-out\u003c/p\u003e \u003cp\u003eMore eligible participants in the ED group (n\u0026thinsp;=\u0026thinsp;16) dropped out than in the control group (n\u0026thinsp;=\u0026thinsp;9) (see Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The difference can be attributed to more ED patients declining before the study phase with the two experimental exercise visits. 118 out of the 120 exercise sessions were completed. Two participants in the ED group terminated the moderate-intensity exercise before completion. This occurred 10 minutes and 19 minutes respectively into the exercise session, both due to the participants perceiving the feeling of exertion as too high (18 and 20 RPE respectively). Data from the participant who stopped after 19 minutes has been included since almost the complete session was performed and after controlling for that it did not affect the analyses.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo our knowledge, this study is the first to investigate the effects of acute exercise on patients with stress-induced exhaustion disorder (ED). Our primary goal was to examine the psychological responses to acute exercise in ED patients and compare them with those in healthy control participants. Our findings show that a short bout of aerobic exercise can alleviate symptoms experienced by ED patients, hence in line with previous research on the effects of exercise in managing symptoms involving patients with depression and anxiety disorders [11, 12, 13]. As expected, ED patients, compared to healthy controls, reported worse levels of fatigue, energy, anxiety, and stress in general, which reflects the common symptoms of ED. The exercise effects in ED patients differed from those in healthy controls in several ways. ED patients perceived the exercise as more strenuous but experienced greater reductions in fatigue and stress immediately after exercise, which was sustained also after a 30-minute rest post-exercise, along with more pronounced energy increases post-exercise. Additionally, we aimed to explore whether the response varied between low and moderate exercise intensities. We found that ED patients reacted with similar psychological responses to both intensities.\u003c/p\u003e \u003cp\u003eDuring the exercise sessions, the ED patients experienced the activity as more strenuous than the healthy controls. This was expected given that mentally fatigued individuals rate exercise as more strenuous [34], and that marked physical weakness is a symptom of ED (ICD-10-SE). Hence, the higher self-reported exertion in ED patients may be attributed to central fatigue [35], an issue reported in studies on similar disorders [36, 37], rather than solely the physiological processes in exercise seen in overall healthy individuals. Central nervous system-related fatigue affects exercise performance together with peripheral fatigue also in healthy individuals but can be more pronounced in disorders such as ME/CFS and depression [36]. Previous studies in ME/CFS patients have shown higher perceived exertion ratings in relation to heart rate during exercise despite no defect in neuromuscular function, which has been attributed in part to central fatigue [37].\u003c/p\u003e \u003cp\u003eInterestingly, the elevation of exertion did not correspond with that of psychological discomfort. Although ED patients reported greater overall psychological discomfort, they did not experience a higher increase in discomfort compared to healthy controls. This is consistent with previous research in women with ED, showing higher overall SUDS ratings but no difference in psychological distress response compared to a control group when exposed to a mental stressor [38]. Hence, ED patients seem to respond similarly to mental and physical stressors in terms of psychological discomfort. As our study measured both perceived exertion and psychological discomfort during the exercise, the complexity of how exercise is experienced was highlighted. The notion that more strenuous physical activity does not necessarily correspond to increased psychological discomfort has support from previous research, which shows that affective displeasure does not correlate linearly with exercise intensity but instead plateaus at higher intensities above the ventilatory threshold [10], typically correlating to RPE ratings around 13 [39].\u003c/p\u003e \u003cp\u003eDespite the exercise being perceived as more strenuous by the ED group, it elicited more beneficial psychological effects post-exercise. Previous research made primarily on healthy individuals has found that acute exercise consistently increases energy [40]. However, results on fatigue are more heterogeneous, showing that fatigue reduction occurs when baseline fatigue is normal or high and when energy increase post-exercise is substantial [40]. The reductions in fatigue and increased energy in ED patients are hence consistent with these results. A study on college students with elevated fatigue [41] found similar reductions in fatigue after exercise at 50% of V̇O\u003csub\u003e2\u003c/sub\u003e max, resembling our study\u0026rsquo;s moderate-intensity exercise, but not at 75% of V̇O\u003csub\u003e2\u003c/sub\u003e max. The fatigue reductions in the ED group contrast with the elevated fatigue in ME/CFS patients post-exercise [42], a condition similar to ED characterized by persistent fatigue. This highlights differences between the two conditions. While ED patients experienced lowered fatigue post-exercise, controls did not, likely due to a floor effect, as their pre-exercise fatigue levels were already low (see Table S8, Additional file 1). In previous acute exercise studies showing fatigue-reducing effects, pre-exercise POMS fatigue scores averaged 6.42 [40], allowing for noticeable reductions.\u003c/p\u003e \u003cp\u003eConversely, the control group showed increased fatigue 30 minutes after moderate-intensity exercise. Typically, post-exercise fatigue increases occur when the baseline fatigue level is low [40], as in this study\u0026rsquo;s control group, but are otherwise also associated with high-intensity and longer-duration exercise [26]. Sustained reductions in fatigue have been observed in both healthy individuals [43] and those with substance abuse [44]. However, a difference from these studies is that participants generally experienced an immediate fatigue-reducing effect, which was not observed in the control group of this study.\u003c/p\u003e \u003cp\u003eBoth groups experienced elevated energy post-exercise, in line with previous research [40]. For ED patients, this effect was significant at both intensities, while for healthy controls, it was significant only at low intensity, though approaching significance at moderate intensity (p\u0026thinsp;=\u0026thinsp;.089). The lack of a pronounced energy increase from moderate-intensity exercise in the control group might contribute to the explanation of the delayed fatigue observed 30 minutes post-exercise, since energy has been shown to moderate changes in fatigue [40].\u003c/p\u003e \u003cp\u003eBesides a significantly more pronounced energy drop from post-exercise to 30 minutes after exercise at moderate intensity for both groups, and elevated fatigue in the control group 30 minutes after moderate-intensity exercise, the short exercise bouts did not produce significantly different psychological responses based on intensity. Previous research on intensity effects on affective states shows mixed results [10]. Many studies report no intensity effects, while others have found varied or negative effects on higher exercise intensities, particularly for energy and fatigue. However, a meta-analysis suggested greater anxiety-reducing effects at higher intensities due to the exposure, habituation, and reappraisal of bodily sensations similar to anxiety reactions (e.g., elevated heart rate, elevated breathing rate) [30]. Consequently, low-intensity exercise usually does not produce beneficial changes in fatigue, energy, and anxiety, as measured in this study. A more mechanistic study design could shed light on the mechanisms underlying these patterns in ED patients.\u003c/p\u003e \u003cp\u003ePrevious research generally shows small reductions in state anxiety [30], and an anxiety-reducing effect of the exercise was also observed in this study. The time x group interaction only approached significance (p\u0026thinsp;=\u0026thinsp;.077), making it uncertain how the two groups differed in their responses, but importantly, the ED group did not show increased anxiety after exercise (see Table S8, Additional file 1). Interestingly, anxiety levels decreased further during the 30-minute rest period following exercise, an effect not observed in previous studies, such as a meta-analysis including the same anxiety measure used here [30], or a recent study on depression patients that included a post-exercise rest period [45]. A partial explanation could be that the rest period was particularly valued by the ED patients due to their symptoms of exhaustion. Although not a part of the data collection protocol, anecdotal data indicated that many ED patients viewed the mandatory rest as a welcome treat. Additionally, the self-selected component of the quiet rest, where participants could choose to rest, sleep, read provided magazines, or bring their own reading material, may have contributed to the rest being viewed as an overall positive experience. The stress response curve was similar to that of anxiety, indicating an overlap between the two constructs. A recent meta-analysis on stress reactivity to a mental stressor found no reliable changes in self-reported stress after acute exercise [46], hence again highlighting the need to study mechanisms underlying responses.\u003c/p\u003e \u003cp\u003eWe believe that the measures 6 and 24 hours after exercise were important, as clinical observations suggest that concerns about delayed post-exercise fatigue and reduced energy often discourage PA in individuals with ED. Recent qualitative research [29] has supported this. Given that the psychological effects of acute exercise are transient, with positive activated affect like energy typically lasting up to 30 minutes [47], we did not expect improvements later in the day or the next morning. However, we considered potential delayed negative psychological effects, similar to those reported by CFS patients [14], especially since ED patients report such expectations [29]. Contrary to these assumptions, neither group showed increased fatigue, anxiety, stress, or decreased energy later in the day or the following morning compared to baseline, which is encouraging findings. It is important to note that this only concerns the short-term effects of single exercise sessions, and no conclusions can be drawn about the effects of repeated exercise. One factor potentially influencing the delayed ratings is the quiet rest post-exercise. It is possible that a rest period after exercise affected the ED group more, since lack of recovery, i.e. \u0026ldquo;psychophysiological unwinding after effort expenditure\u0026rdquo; [48] is central in the link between exposure to stressors and negative effects of stress. Hence, the delayed measurements show how exercise followed by 30 minutes of quiet rest affected the participants, not solely exercise.\u003c/p\u003e \u003cp\u003eFatigue, being a central clinical characteristic of ED (3, 29], can be defined as a \u0026ldquo;persistent sense of physical, emotional, and/or cognitive tiredness or exhaustion\u0026rdquo; [26] and implies a lack of ability to initialize and maintain mental and physical tasks that require effort and self-motivation. This has implications for the real-world transferability of the high compliance and low exercise sessions drop-out as participants had support in initiating the exercise, and researchers were present during sessions. Social support is an important factor for ED patients with less exercise experience in establishing an exercise routine [49]. Previous research shows that mental fatigue affects the choice of sedentary activities over physical activities, with the only exception being low intensities [50]. So although our results have positive short-term symptom management implications, the effort required to initiate and maintain short exercise sessions might be a considerable obstacle. This must be addressed in intervention design.\u003c/p\u003e \u003cp\u003eThere is limited data on how generalizable acute exercise studies are to long-term exercise effects. Thus, our study does not answer how ED patients would react psychologically to habitual exercise, warranting further studies. Acute exercise effects can however increase the chance of continuous exercise adherence, with previous research showing that lower levels of fatigue post-exercise correlate with more frequent exercise months later [51]. The beneficial effects of single exercise sessions observed here might thus potentially increase compliance with exercise in ED patients, by enhancing external motivation and limiting negative expectations of exercise consequences.\u003c/p\u003e \u003cp\u003ePotential limitations\u003c/p\u003e \u003cp\u003eOne factor not manipulated in the study was the duration of exercise, which is another aspect influencing the psychological response to exercise. A meta-study on acute exercise effects on fatigue and energy [26] found that while exercise consistently increases feelings of energy, fatigue increases with longer duration, specifically beyond 20 minutes. However, a study comparing various combinations of durations of acute exercise (5\u0026ndash;60 minutes) and subsequent rest periods showed no difference in fatigue ratings [43]. The exercise bouts in that study produced mean RPE ratings between 9.7 and 11.9, hence comparable to the low-intensity exercise in our study (see Table S7, Additional file 1). But considering that fatigue is central to ED, it might be that longer durations of exercise beyond 20 minutes affect this group more than many other populations. This highlights that the combination of intensity and duration affects the psychological response and must be considered jointly.\u003c/p\u003e \u003cp\u003eEstimation of aerobic capacity was performed using an indirect method. As such, it contains errors larger than those related to direct or maximal test methods. However, maximal tests were deemed unsuitable for the ED group and any comparison to the controls could have been attributed to differences in ability to reach maximal effort. Nonetheless, the errors related to the submaximal, indirect test may have resulted in over- or underestimations, potentially causing participants in both groups to work at a higher or lower work rate than the intended 40% and 55%. We regard this as a random error that increases the variance and potentially results in an underestimation of real changes or differences, but not creating systematic group or time differences. Concerning blood pressure, we have no record on which arm it was measured, so there may have been variations. Since these measures were used solely for exclusion purposes and no participant was approaching the exclusion limit, we consider this a minor limitation. Another limitation regarding internal validity is that some participants may have slept during the resting period after the exercise bouts, which was not systematically registered.\u003c/p\u003e \u003cp\u003eWe did not include a measure of positive affect during exercise, which could have given a more comprehensive understanding of the psychological response [10]. Future studies should address this. However, one strength of our study is the inclusion of some psychological measures during exercise, which is often overlooked in acute exercise research. Since psychological responses are dynamic and not linear, this, combined with delayed measurements, provides a more complete picture of the psychological response to exercise in ED patients.\u003c/p\u003e \u003cp\u003eThe sample consisted primarily of women, with two men in each group. This limits the generalizability of the results to men. Gender differences in psychological responses to acute exercise are understudied, but one study [52] on young adults found such differences, with women showing greater improvements than men in fatigue and energy after 30 minutes of vigorous aerobic exercise. Generally, those with worse baseline values for variables such as anxiety [30], and energy level [47] experience significant beneficial effects of the exercise. Since women reported higher baseline problems with these variables, the observed differences might be due to the larger potential for benefits, rather than to gender differences.\u003c/p\u003e \u003cp\u003eExperimental studies in a laboratory environment always have the issue of generalizability or external validity. Factors that could have contributed to negative experiences during the exercise (e.g. level of exertion and psychological discomfort) include that the exercise took place in a windowless room without distractions such as music or scenery. Exercising outdoors vs. indoors has been proposed to elicit lower RPE, and listening to music also has been shown to have beneficial effects on RPE [53]. The presence of a researcher during exercise might have affected the participants. Non-systematic observations indicated that some ED patients felt nervous about exercising, especially at moderate intensity, but felt safer in the controlled situation with a researcher present.\u003c/p\u003e \u003cp\u003eHowever, a strength of the study is the comparison of the ED patients to a healthy control group, which allowed reliable conclusions about the psychological response to exercise specific to ED patients. This makes it easier to adjust the exercise recommendations existing for a healthy population. Additionally, the counterbalancing of exercise session order based on intensity enhances the reliability of conclusions about intensity effects, avoiding potential novelty effects on psychological discomfort, stress, and anxiety.\u003c/p\u003e \u003cp\u003eLastly, we had concerns that only ED patients with low symptom levels and limited impairment in important areas of functioning would participate in the study. This was however not substantiated, as demonstrated in the baseline exhaustion ratings and sickness absence (see Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The large interest shown by individuals with an ED diagnosis in participating in the study indicates a large interest among them in exercise as an intervention.\u003c/p\u003e \u003cp\u003eFurther research\u003c/p\u003e \u003cp\u003eThis study aimed to shed some initial light on how acute exercise affects patients with ED, but several questions remain unanswered. Future studies could include exercise with different durations and higher exercise intensities, as well as explore the influence of different durations of rest post-exercise. The focus was on psychological responses to acute exercise, without exploring underlying processes that govern these responses in ED patients. Studies with a mechanistic focus can contribute to understanding the processes that underlie the psychological changes during and after exercise in ED patients. Research with a focus on susceptibility profiles is also needed, enabling more tailored exercise programs for the different needs of different ED patients. Potential moderators could include symptom severity, exercise level, fitness level, and BMI. While this study focused on aerobic exercise, other types of training, such as strength training, could also have beneficial psychological effects, and warrant further research.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe results from this study, showing that exercise at both low and moderate intensity can have short-term symptom benefits for ED patients, without adverse delayed symptom effects, are promising. Given that ED patients often fail to reach WHO recommendations for physical activity [54] these beneficial acute effects can be guidance in designing interventions that enhance long-term exercise adherence [10].\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eAll participants received written information about the study, were given an opportunity to ask questions, and provided informed consent prior to inclusion. The study was approved by the Swedish Ethical Review Authority (Approval Nr. 2022-04943-01) and was conducted in accordance with the ethical principles of the Declaration of Helsinki.\u003c/p\u003e\n\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\n\u003cp\u003eAvailability of data and materials\u003c/p\u003e\n\u003cp\u003eThe data that was analyzed or produced in this study is not openly accessible due to Swedish legislation (the Swedish Ethical Review Act: 2003:460) but the authors can provide access upon reasonable request. For such inquiries, please contact VB.\u003c/p\u003e\n\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThis study was conducted as part of E-PABS; a center of excellence in physical activity, healthy brain functions, and sustainability, based at The Swedish School of Sport and Health Sciences. The work was supported by the Knowledge Foundation (Grant no GIH 2021/8). The study sponsor had no role in the study design, collection, analysis, or interpretation of data of the study. Further, they had no role in the writing of the report or decision to submit the paper for publication.\u003c/p\u003e\n\n\u003cp\u003eAuthors\u0026rsquo; contributions\u003c/p\u003e\n\u003cp\u003eVB and RPA developed the initial idea for the study. VB, JK, RPA, and \u0026Ouml;E contributed to the design of the study in its final form. Data collection was performed by JK, together with individuals named in section Acknowledgements. JK conducted the statistical analyses with substantial input from VB, RPA, and \u0026Ouml;E. JK wrote the manuscript, and all authors provided critical revisions and approved the final version of the manuscript for submission.\u003c/p\u003e\n\n\u003cp\u003eAcknowledgments\u003c/p\u003e\n\u003cp\u003eThe authors extend their sincere gratitude to all participants who made this study possible. Special thanks also to Amanda L\u0026ouml;nn, who assisted with administration and practical aspects of data collection as well as contributed valuable input on the study protocols. We also want to acknowledge Emma Fors\u0026eacute;n Mantilla, Erik von Campenhausen, and Marcus Colling Holmberg for their efforts during the data collection.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eF\u0026ouml;rs\u0026auml;kringskassan. 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Glob Health Action. 2023 Dec 31;16(1):2212950.\u003c/li\u003e\n\u003cli\u003eHarris S, Stratford P, Bray SR. Is It Really Worth the Effort? Examining the Effects of Mental Fatigue on Physical Activity Effort Discounting. J Sport Exerc Psychol. 2022 Oct 21;44(6):409-419. \u003c/li\u003e\n\u003cli\u003eKwan BM, Bryan A. In-task and post-task affective response to exercise: translating exercise intentions into behaviour. Br J Health Psychol. 2010 Feb;15(Pt 1):115-31.\u003c/li\u003e\n\u003cli\u003eMcDowell CP, Campbell MJ, Herring MP. Sex-Related Differences in Mood Responses to Acute Aerobic Exercise. Med Sci Sports Exerc. 2016 Sep;48(9):1798-802. \u003c/li\u003e\n\u003cli\u003eHutchinson, J. C. (2021). Perceived effort and exertion. In Z. Zenko \u0026amp; L. Jones (Eds.), Essentials of exercise and sport psychology: An open access textbook (pp. 294\u0026ndash;315). Society for Transparency, Openness, and Replication in Kinesiology. https://doi.org/10.51224/B1013\u003c/li\u003e\n\u003cli\u003eLindeg\u0026aring;rd A, Jonsdottir IH, B\u0026ouml;rjesson M, Lindwall M, Gerber M. Changes in mental health in compliers and non-compliers with physical activity recommendations in patients with stress-related exhaustion. BMC Psychiatry. 2015 Nov 4;15:272.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-psychiatry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bpsy","sideBox":"Learn more about [BMC Psychiatry](http://bmcpsychiatry.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bpsy/default.aspx","title":"BMC Psychiatry","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Exercise, Acute, Exhaustion disorder, Stress, Fatigue, Energy, Anxiety, Exercise intensity","lastPublishedDoi":"10.21203/rs.3.rs-5217618/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5217618/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eUnderstanding acute psychological responses to physical exercise is important since they likely influence the initiation and maintenance of this behavior. Given its effectiveness in reducing symptoms in various psychological disorders, physical exercise should be further explored in Exhaustion Disorder (ED; ICD-10-SE: F43.8A), a condition characterized by persistent exhaustion following long-term psychosocial stress. Currently, no studies are available on the psychological effects of acute exercise in ED patients.\u003c/p\u003e\u003ch2\u003eAims\u003c/h2\u003e \u003cp\u003eThis study aims to (1) investigate the psychological responses to acute exercise in ED patients compared to healthy controls and (2) determine if these responses differ between low and moderate exercise intensities.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe conducted a two-armed cross-over trial in two groups: ED patients (n\u0026thinsp;=\u0026thinsp;30) and healthy controls (n\u0026thinsp;=\u0026thinsp;30). On two separate occasions, participants completed a 22-minute exercise at low or moderate intensity on a cycle ergometer, in randomized order. The main outcome was perceived fatigue, and secondary outcomes were feelings of energy, anxiety, stress, perceived exertion, and perceived psychological discomfort, all measured before, during, and up to 24 hours after exercise. Effects of the exercise conditions were assessed with repeated measures analysis of variance.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eED patients reported higher exertion and psychological discomfort before and during exercise, higher fatigue, anxiety, and stress but lower energy throughout the trial compared to the controls. ED patients experienced more reduced fatigue and stress after both intensities (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), and a more elevated energy after moderate-intensity exercise compared to controls (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). No interactions between groups were found for anxiety over time. No differences were observed between pre-exercise and 6 hours or 24 hours post-exercise in any variables. The only intensity effect (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) in the ED patients was a more pronounced energy decline 30 minutes after moderate-intensity exercise.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eA 22-minute exercise was perceived as more strenuous by patients with exhaustion disorder and generated greater improvements in feelings of fatigue, energy, and stress compared to healthy individuals, without delayed negative changes. These findings can inform intervention design and guide clinical practice.\u003c/p\u003e\u003ch2\u003eTrial registration\u003c/h2\u003e \u003cp\u003eThe study was retrospectively registered on 05/30/2024 at Clinical Trials.gov, with trial registration number 2022-04943-01.\u003c/p\u003e","manuscriptTitle":"Psychological Responses to Acute Exercise in Patients With Stress-induced Exhaustion Disorder: a Cross-over Randomized Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-18 17:24:01","doi":"10.21203/rs.3.rs-5217618/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-11-25T06:56:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-25T00:21:03+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-08T12:03:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"101709407909420841935131360433560350682","date":"2024-11-08T09:40:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"300132842857344356354277079515145169587","date":"2024-10-27T10:19:16+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-10-25T07:54:02+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-10-14T18:49:12+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-10-12T17:06:12+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-10-12T17:05:18+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Psychiatry","date":"2024-10-07T10:59:07+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-psychiatry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bpsy","sideBox":"Learn more about [BMC Psychiatry](http://bmcpsychiatry.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bpsy/default.aspx","title":"BMC Psychiatry","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"924b6e63-c484-48c1-8237-6e987a5b670b","owner":[],"postedDate":"December 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-01-27T16:05:11+00:00","versionOfRecord":{"articleIdentity":"rs-5217618","link":"https://doi.org/10.1186/s12888-025-06484-1","journal":{"identity":"bmc-psychiatry","isVorOnly":false,"title":"BMC Psychiatry"},"publishedOn":"2025-01-24 15:58:18","publishedOnDateReadable":"January 24th, 2025"},"versionCreatedAt":"2024-12-18 17:24:01","video":"","vorDoi":"10.1186/s12888-025-06484-1","vorDoiUrl":"https://doi.org/10.1186/s12888-025-06484-1","workflowStages":[]},"version":"v1","identity":"rs-5217618","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5217618","identity":"rs-5217618","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}