Chronotropic incompetence of the heart is associated with exercise intolerance in patients with schizophrenia.

The elevated cardiovascular risk of patients with schizophrenia contributes to a reduced life expectancy of 15-20years. This study investigated whether cardiac autonomic dysfunction (CADF) in schizophrenia is related to chronotropic incompetence, an established cardiovascular risk marker. We investigated thirty-two patients suffering from paranoid schizophrenia and thirty-two control subjects matched for age, sex, body mass index and fat free mass. A cardiopulmonary exercise test (CPET) was performed to study heart rate responses to exercise as well as submaximal (ventilatory threshold 1, VT1) and maximal endurance capacities (peak oxygen consumption, VO2peak; peak power output, Ppeak). In addition, epinephrine and norepinephrine levels were assessed in a subset of patients. Fitness parameters were significantly reduced in all patients. Most investigated physiological parameters were significantly different at rest as well as during peak exercise being in line with previously described CADF in schizophrenia. In particular, 14 out of 32 patients were classified as chronotropically incompetent whereas no control subject was below the cut-off value. In addition, a positive correlation of a slope reflecting chronotropic incompetence with peak oxygen uptake (p<0.001) was observed in patients only indicating a close correlation to the lack of physical fitness. The catecholamine increase was reduced in patients after exercise. This study identified a novel cardiac risk factor in patients with schizophrenia. Moreover, it seems to be associated with reduced physical fitness and indicates targets for exercise intervention studies. Future studies are warranted to elucidate pathophysiological mechanisms of this cardiac condition.

Changes in fMRI activation in anterior hippocampus and motor cortex during memory retrieval after an intense exercise intervention.

Strong evidence indicates that regular aerobic training induces beneficial effects on cognitive functions. The present controlled fMRI study was designed to investigate the impact of a short-term intense aerobic exercise on the pattern of functional activation during the retrieval of learned pair-associates in 17 young and healthy male adults compared to 17 matched control subjects. We further aimed to relate putative changes in hippocampal activation to postulated changes in the exercised-induced brain derived neurotrophic factor (BDNF). The supervised exercise program was performed on a bicycle ergometer and lasted six weeks, with three aerobic sessions per week. We found profound improvement of physical fitness in most subjects indicated by the target parameter 'individual anaerobic threshold'. Significant improvements in the cognitive performance were detected in the exercise group, but also in the control group. We observed significant differences in the activation pattern of the left anterior hippocampus during the pair-associates task after the intervention. We could also show a significant positive correlation between changes in exercise-induced BDNF and left anterior hippocampal activation. Moreover, we observed the brain's motor network to be significantly stronger activated after the exercise intervention. Thus, our results suggest BDNF dependent activation changes of the hippocampus in addition to previously described structural changes after exercise.

Hippocampal-Brainstem Connectivity Associated with Vagal Modulation after an Intense Exercise Intervention in Healthy Men.

Regular physical exercise leads to increased vagal modulation of the cardiovascular system. A combination of peripheral and central processes has been proposed to underlie this adaptation. However, specific changes in the central autonomic network have not been described in human in more detail. We hypothesized that the anterior hippocampus known to be influenced by regular physical activity might be involved in the development of increased vagal modulation after a 6 weeks high intensity intervention in young healthy men (exercise group: n = 17, control group: n = 17). In addition to the determination of physical capacity before and after the intervention, we used resting state functional magnetic resonance imaging and simultaneous heart rate variability assessment. We detected a significant increase of the power output at the anaerobic threshold of 11.4% (p < 0.001), the maximum power output Pmax of 11.2% (p < 0.001), and VO2max adjusted for body weight of 4.7% (p < 0.001) in the exercise group (EG). Comparing baseline (T0) and post-exercise (T1) values of parasympathetic modulation of the exercise group, we observed a trend for a decrease in heart rate (p < 0.06) and a significant increase of vagal modulation as indicated by RMSSD (p < 0.026) during resting state. In the whole brain analysis, we found that the connectivity pattern of the right anterior hippocampus (aHC) was specifically altered to the ventromedial anterior cortex, the dorsal striatum and to the dorsal vagal complex (DVC) in the brainstem. Moreover, we observed a highly significant negative correlation between increased RMSSD after exercise and decreased functional connectivity from the right aHC to DVC (r = -0.69, p = 0.003). This indicates that increased vagal modulation was associated with functional connectivity between aHC and the DVC. In conclusion, our findings suggest that exercise associated changes in anterior hippocampal function might be involved in increased vagal modulation.

Hippocampal structure, metabolism, and inflammatory response after a 6-week intense aerobic exercise in healthy young adults: a controlled trial.

Interventional studies suggest that changes in physical fitness affect brain function and structure. We studied the influence of high intensity physical exercise on hippocampal volume and metabolism in 17 young healthy male adults during a 6-week exercise program compared with matched controls. We further aimed to relate these changes to hypothesized changes in exercised-induced brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). We show profound improvement of physical fitness in most subjects and a positive correlation between the degree of fitness improvement and increased BDNF levels. We unexpectedly observed an average volume decrease of about 2%, which was restricted to right hippocampal subfields CA2/3, subiculum, and dentate gyrus and which correlated with fitness improvement and increased BDNF levels negatively. This result indicates that mainly those subjects who did not benefit from the exercise program show decreased hippocampal volume, reduced BDNF levels, and increased TNF-α concentrations. While spectroscopy results do not indicate any neuronal loss (unchanged N-acetylaspartate levels) decreased glutamate-glutamine levels were observed in the right anterior hippocampus in the exercise group only. Responder characteristics need to be studied in more detail. Our results point to an important role of the inflammatory response after exercise on changes in hippocampal structure.

The relation of autonomic function to physical fitness in patients suffering from alcohol dependence.

BACKGROUND: Reduced cardio-vascular health has been found in patients suffering from alcohol dependence. Low cardio-respiratory fitness is an independent predictor of cardio-vascular disease. METHODS: We investigated physical fitness in 22 alcohol-dependent patients 10 days after acute alcohol withdrawal and compared results with matched controls. The standardized 6-min walk test (6 MWT) was used to analyze the relationship of autonomic dysfunction and physical fitness. Ventilatory indices and gas exchanges were assessed using a portable spiroergometric system while heart rate recordings were obtained separately. We calculated walking distance, indices of heart rate variability and efficiency parameters of heart rate and breathing. In addition, levels of exhaled carbon monoxide were measured in all participants to account for differences in smoking behaviour. Multivariate analyses of variance (MANOVA) were performed to investigate differences between patients and controls with regard to autonomic and efficiency parameters. RESULTS: Patients walked a significantly shorter distance in comparison to healthy subjects during the 6 MWT. Significantly decreased heart rate variability was observed before and after the test in patients when compared to controls, while no such difference was observed during exercise. The efficiency parameters indicated significantly reduced efficiency in physiological regulation when the obtained parameters were normalized to the distance. DISCUSSION: The 6 MWT is an easily applied instrument to measure physical fitness in alcohol dependent patients. It can also be used during exercise interventions. Reduced physical fitness, as observed in our study, might partly be caused by autonomic dysfunction, leading to less efficient regulation of physiological processes during exercise.

Exercise reveals the interrelation of physical fitness, inflammatory response, psychopathology, and autonomic function in patients with schizophrenia.

Maintaining and improving fitness are associated with a lower risk of premature death from cardiovascular disease. Patients with schizophrenia are known to exercise less and have poorer health behaviors than average. Physical fitness and physiological regulation during exercise tasks have not been investigated to date among patients with schizophrenia. We studied autonomic modulation in a stepwise exhaustion protocol in 23 patients with schizophrenia and in matched controls, using spirometry and lactate diagnostics. Parameters of physical capacity were determined at the aerobic, anaerobic, and vagal thresholds (VT), as well as for peak output. VT was correlated with psychopathology, as assessed by the Positive and Negative Syndrome Scale, with the inflammatory markers IL-1ß, IL-6, and TNF-α and with peak output. The MANOVA for heart and breathing rates, as well as for vagal modulation and complexity behavior of heart rate, indicated a profound lack of vagal modulation at all intensity levels, even after the covariate carbon monoxide concentration was introduced as a measure of smoking behavior. Significantly decreased physical capacity was demonstrated at the aerobic, anaerobic, and VT in patients. After the exercise task, reduced vagal modulation in patients correlated negatively with positive symptoms and with levels of IL-6 and TNF-α. This study shows decreased physical capacity in patients with schizophrenia. Upcoming intervention studies need to take into account the autonomic imbalance, which might predispose patients to arrhythmias during exercise. Results of inflammatory parameters are suggestive of a reduced activity of the anti-inflammatory cholinergic pathway in patients, leading to a pro-inflammatory state.