Jacob D. Meyer

Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease characterized by intense and debilitating fatigue not due to physical activity that has persisted for at least 6 months, post-exertional malaise, unrefreshing sleep, and accompanied by a number of secondary symptoms, including sore throat, memory and concentration impairment, headache, and muscle/joint pain. In patients with post-exertional malaise, significant worsening of symptoms occurs following physical exertion and exercise challenge serves as a useful method for identifying biomarkers for exertion intolerance. Evidence suggests that intestinal dysbiosis and systemic responses to gut microorganisms may play a role in the symptomology of ME/CFS. As such, we hypothesized that post-exertion worsening of ME/CFS symptoms could be due to increased bacterial translocation from the intestine into the systemic circulation. To test this hypothesis, we collected symptom reports and blood and stool samples from ten clinically characterized ME/CFS patients and ten matched healthy controls before and 15 minutes, 48 hours, and 72 hours after a maximal exercise challenge. Microbiomes of blood and stool samples were examined. Stool sample microbiomes differed between ME/CFS patients and healthy controls in the abundance of several major bacterial phyla. Following maximal exercise challenge, there was an increase in relative abundance of 6 of the 9 major bacterial phyla/genera in ME/CFS patients from baseline to 72 hours post-exercise compared to only 2 of the 9 phyla/genera in controls (p = 0.005). There was also a significant difference in clearance of specific bacterial phyla from blood following exercise with high levels of bacterial sequences maintained at 72 hours post-exercise in ME/CFS patients versus clearance in the controls. These results provide evidence for a systemic effect of an altered gut microbiome in ME/CFS patients compared to controls. Upon exercise challenge, there were significant changes in the abundance of major bacterial phyla in the gut in ME/CFS patients not observed in healthy controls. In addition, compared to controls clearance of bacteria from the blood was delayed in ME/CFS patients following exercise. These findings suggest a role for an altered gut microbiome and increased bacterial translocation following exercise in ME/CFS patients that may account for the profound post-exertional malaise experienced by ME/CFS patients.

Influence of exercise intensity for improving depressed mood in depression: a dose-response study

INTRODUCTION Exercise effectively improves mood in major depressive disorder (MDD), but the optimal exercise stimulus to improve depressed mood is unknown. PURPOSE To determine the dose-response relationship of acute exercise intensity with depressed mood responses to exercise in MDD. We hypothesized that the acute response to exercise would differ between light, moderate, and hard intensity exercise with higher intensities yielding more beneficial responses. METHODS Once weekly, 24 women (age: 38.6±14.0) diagnosed with MDD underwent a 30-minute session at one of three steady-state exercise intensities (light, moderate, hard; rating of perceived exertion 11, 13 or 15) or quiet rest on a stationary bicycle. Depressed mood was evaluated with the Profile of Mood States before, 10 and 30 minutes post-exercise. RESULTS Exercise reduced depressed mood 10 and 30 minutes following exercise, but this effect was not influenced by exercise intensity. Participants not currently taking antidepressants (n=10) had higher baseline depression scores, but did not demonstrate a different antidepressant response to exercise compared to those taking antidepressants. CONCLUSIONS To acutely improve depressed mood, exercise of any intensity significantly improved feelings of depression with no differential effect following light, moderate, or hard exercise. Pharmacological antidepressant usage did not limit the mood-enhancing effect of acute exercise. Acute exercise should be used as a symptom management tool to improve mood in depression, with even light exercise an effective recommendation. These results need to be replicated and extended to other components of exercise prescription (e.g., duration, frequency, mode) to optimize exercise guidelines for improving depression.

Responses to Exercise Differ For Chronic Fatigue Syndrome Patients with Fibromyalgia

UNLABELLED Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are chronic multisymptom illnesses with substantial clinical and diagnostic overlap. We have previously shown that, when controlling for aerobic fitness and accounting for comorbid FM, CFS patients do not exhibit abnormal cardiorespiratory responses during maximal aerobic exercise compared with healthy controls, despite differences in pain and exertion. PURPOSE The purpose of the present study was to examine cardiac and perceptual responses to steady-state submaximal exercise in CFS patients and healthy controls. METHODS Twenty-one CFS patients (13 CFS with comorbid FM (CFS + FM)) and 14 controls completed 20 min of submaximal cycling exercise. Impedance cardiography was used to determine cardiac responses during exercise. Systolic blood pressure (SBP), RPE, and leg muscle pain were also measured. Data were analyzed using a doubly multivariate, repeated-measures MANOVA to model the exercise response. RESULTS There was a significant multivariate time-by-group interaction (P < 0.05). The CFS + FM group exhibited an exercise response characterized by higher stroke index, ventilatory equivalents for oxygen and carbon dioxide and RPE, lower SBP, and similar HR responses compared to controls. CONCLUSIONS The present results extend on our previous work with maximal exercise and show that CFS and CFS + FM differ in their responses to steady-state exercise. These results highlight the importance of accounting for comorbid conditions when conducting CFS research, particularly when examining psychophysiological responses to exercise.

Neural consequences of post-exertion malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Post exertion malaise is one of the most debilitating aspects of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, yet the neurobiological consequences are largely unexplored. The objective of the study was to determine the neural consequences of acute exercise using functional brain imaging. Fifteen female Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients and 15 healthy female controls completed 30min of submaximal exercise (70% of peak heart rate) on a cycle ergometer. Symptom assessments (e.g. fatigue, pain, mood) and brain imaging data were collected one week prior to and 24h following exercise. Functional brain images were obtained during performance of: 1) a fatiguing cognitive task - the Paced Auditory Serial Addition Task, 2) a non-fatiguing cognitive task - simple number recognition, and 3) a non-fatiguing motor task - finger tapping. Symptom and exercise data were analyzed using independent samples t-tests. Cognitive performance data were analyzed using mixed-model analysis of variance with repeated measures. Brain responses to fatiguing and non-fatiguing tasks were analyzed using linear mixed effects with cluster-wise (101-voxels) alpha of 0.05. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients reported large symptom changes compared to controls (effect size ≥0.8, p<0.05). Patients and controls had similar physiological responses to exercise (p>0.05). However, patients exercised at significantly lower Watts and reported greater exertion and leg muscle pain (p<0.05). For cognitive performance, a significant Group by Time interaction (p<0.05), demonstrated pre- to post-exercise improvements for controls and worsening for patients. Brain responses to finger tapping did not differ between groups at either time point. During number recognition, controls exhibited greater brain activity (p<0.05) in the posterior cingulate cortex, but only for the pre-exercise scan. For the Paced Serial Auditory Addition Task, there was a significant Group by Time interaction (p<0.05) with patients exhibiting increased brain activity from pre- to post-exercise compared to controls bilaterally for inferior and superior parietal and cingulate cortices. Changes in brain activity were significantly related to symptoms for patients (p<0.05). Acute exercise exacerbated symptoms, impaired cognitive performance and affected brain function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients. These converging results, linking symptom exacerbation with brain function, provide objective evidence of the detrimental neurophysiological effects of post-exertion malaise.

Psychobiological Responses to Preferred and Prescribed Intensity Exercise in Major Depressive Disorder.

Exercise acutely improves mood in major depressive disorder (MDD). However, it is unknown whether benefits differ depending on whether exercise intensity is self-selected or prescribed. PURPOSE This study aimed to compare psychological and biological responses to preferred and prescribed steady-state exercise intensities to a patient-selected preferred intensity. METHOD Female adults (N = 24, age = 38.6 ± 14.0 yr) diagnosed with MDD completed four 30-min sessions of cycling exercise at three prescribed intensities (RPE of 11, 13, and 15) and one session with a self-selected intensity (preferred). Order was randomized and counterbalanced. Depressed mood (DM) was evaluated before, 10 min, and 30 min postexercise using the Profile of Mood States. Serum brain-derived neurotrophic factor (BDNF) was measured before and within 10 min postexercise. Changes in BDNF and DM for the preferred session were compared with the following prescribed sessions: 1) performed at the most similar intensity (matched on RPE; closest) and 2) with the greatest improvement in DM (greatest). RESULTS Compared with the preferred session, improvement in DM was significantly larger after the greatest session (30 min postexercise: -11.8 ± 7.4 vs -3.4 ± 4.8), and the BDNF response was significantly greater after the closest session (5.4 ± 6.9 vs -1.4 ± 9.8 ng·mL). CONCLUSIONS Permitting patients to select their own exercise intensity did not maximize improvements in mood. Further, preferred intensity exercise was also associated with a smaller BDNF response. Overall, the results suggest that exercise undertaken to improve mood should be prescribed on an individual basis in MDD and not necessarily based on the patients preferred intensity. Clinicians, psychologists, and other practitioners should consider providing clear exercise intensity recommendations for symptom management in depression rather than allowing patients to self-select their intensity.

Post-exertion malaise in chronic fatigue syndrome: symptoms and gene expression

Background: A primary complaint of chronic fatigue syndrome (CFS) patients is post-exertion malaise, which is a worsening of symptoms following activities such as exercise. Purpose: To examine the link between gene expression for metabolite, adrenergic, immune, and glucocorticoid receptors on leukocytes and symptoms (pain, fatigue, and mood) following a maximal exercise test. Methods: Thirteen CFS patients and 11 healthy participants matched on age and fitness underwent blood draws and completed questionnaires immediately before, and 15 minutes, 48 hours, and 72 hours following, maximal exercise. Symptom and genetic measures collected before and after exercise were compared using a doubly multivariate repeated-measures analysis of variance. Results: This comparison of CFS and healthy participants resulted in a significant multivariate main effect for Group (p < 0.05). Univariate analyses indicated group differences for adrenergic α-2A and glucocorticoid (NR3C1) receptor messenger ribonucleic acid and symptoms of fatigue and confusion. Changes in gene expression were significantly correlated with symptoms. Conclusions: Results suggest that increased glucocorticoid sensitivity may contribute to the symptoms of post-exertion malaise in CFS. As NR3C1 interacts with other transcription factors, investigating the resulting cascades may lead to greater understanding of the biological mechanism of post-exertion malaise. This finding, if confirmed, could lead to novel approaches to prevent symptom exacerbation in CFS.

Relationships between cardiorespiratory fitness, hippocampal volume, and episodic memory in a population at risk for Alzheimer's disease

Cardiorespiratory fitness (CRF) has been shown to be related to brain health in older adults. In individuals at risk for developing Alzheimers disease (AD), CRF may be a modifiable risk factor that could attenuate anticipated declines in brain volume and episodic memory. The objective of this study was to determine the association between CRF and both hippocampal volume and episodic memory in a cohort of cognitively healthy older adults with familial and/or genetic risk for Alzheimers disease (AD).

Meeting physical activity recommendations may be protective against temporal lobe atrophy in older adults at risk for Alzheimer's disease

Physical activity (PA) is associated with brain health in older adults. However, it is unknown whether the current physical activity recommendations (PAR) impart substantive benefit. The objective of this study was to compare temporal lobe volumes between older adults who met PAR and those who did not.

Relationships between serum BDNF and the antidepressant effect of acute exercise in depressed women

OBJECTIVE Brain-derived neurotrophic factor (BDNF) has recently emerged as one potential mechanism with which exercise improves mood in major depressive disorder (MDD). This study examined the relationship between changes in serum total BDNF and mood following acute exercise in MDD. It was hypothesized that acute exercise would increase BDNF in an intensity-dependent manner and that changes in BDNF would be significantly related to improvement in depressed mood post-exercise. METHODS Twenty-four women (age: 38.6±14.0years) with MDD exercised for 30min on a stationary bicycle at light, moderate and hard exercise intensities and performed a quiet rest session using a within-subjects, randomized and counter-balanced design. Before, 10 and 30min after each session, participants completed the profile of mood states (POMS). Blood was drawn before and within 10min after completion of each session and serum total BDNF (sBDNF) was measured by enzyme-linked immunosorbent assay. Acute exercise-induced changes in POMS Depression and sBDNF were analyzed via 4 session (quiet rest, light, moderate, hard) by 2 measurement (pre, post) ANOVA. Secondary analyses examined the effects of baseline mood and antidepressant usage on sBDNF. RESULTS Exercise resulted in an acute improvement in depressed mood that was not intensity dependent (p>0.05), resulting in significant acute increases in sBDNF (p=0.006) that were also not intensity-dependent (p>0.05). Acute changes in sBDNF were not significantly correlated to changes in POMS depression at 10m (r=-0.171, p=0.161) or 30m (r=-0.151, p=0.215) post-exercise. The fourteen participants taking antidepressant medications exhibited lower post-exercise sBDNF (p=0.015) than the participants not currently taking antidepressants, although mood responses were similar. CONCLUSION Acute exercise is an effective mood-enhancing stimulus, although sBDNF does not appear to play a role in this short-term response. Patients who are not currently taking antidepressant medications and those who have greater pre-exercise depression may experience a greater sBDNF response to exercise, but the clinical significance of this is currently unclear. Circulating BDNF levels are unlikely to be altered by steady-state acute exercise in a linear dose-dependent manner. This does not eliminate its potential relevance in the antidepressant response to chronic exercise training, but suggests that other mechanisms are involved in the acute affective response to exercise in depression.

Symptom variability following acute exercise in myalgic encephalomyelitis/chronic fatigue syndrome: a perspective on measuring post-exertion malaise

ABSTRACT Background: Consensus for an operational definition of post-exertion malaise (PEM) and which symptoms best characterize PEM has not been established and may be due to variability within and between studies. Purpose: Determine the magnitude of the effect of maximal and submaximal physical exertion on multiple myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) symptoms that are associated with PEM and explore variability among two studies in which mood, fatigue, and pain symptoms were measured before and after exercise. Methods: Symptoms were measured before, and 48 and 72 hours after exercise in study 1 (ME/CFS = 13; Controls = 11) and before and 24 hours after exercise in study 2 (ME/CFS = 15, Controls = 15). Between-study variability was examined by comparing Hedges d effect sizes (95% CI) from studies 1 and 2. Within-patient group variability was examined via inspection of dot density plots. Results: In study 1, large increases in general fatigue (Δ = 1.05), reduced motivation (Δ = 0.93), feelings of fatigue (Δ = 0.90), feelings of confusion (Δ = 0.93), and total mood disturbance (Δ = 0.90) were found at 72 hours. In study 2, a large increase in affective/sensory pain (Δ = 0.79) was found at 24 hours. Dot density plots in both studies revealed substantial variability among people with ME/CFS relative to healthy control participants. Conclusions: PEM symptoms are variable among people with ME/CFS and several gaps in the literature need to be addressed before guidelines for measuring PEM in the clinical or research setting can be established.