Michael T. Bergen

Metabolic and cardiovascular effects of a progressive exercise test in patients with chronic fatigue syndrome

PURPOSE To evaluate the aerobic power (as maximum volume of oxygen consumed [VO2 max]) of women with chronic fatigue syndrome (CFS). PATIENTS AND METHODS Twenty-one women with CFS and 22 sedentary healthy controls (CON) were studied at the CFS Cooperative Research Center Exercise Laboratory at the VA Medical Center, East Orange, New Jersey. Performance was measured on an incremental treadmill protocol walking to exhaustion. Expired gases were analyzed by a metabolic system, heart rate was recorded continuously, and ratings of perceived exertion (RPE) were taken at each workload. The groups were divided into those who achieved VO2 max (CFS-MAX and CON-MAX) and those who stopped at a submaximal level (CFS-NOMAX and CON-NOMAX) by using standard criteria. RESULTS Seventeen CON and 10 CFS subjects achieved VO2 max. The VO2 max (mL/kg/min) of the CFS-MAX (28.1 +/- 5.1) was lower than that of the CON-MAX (32.1 +/- 4.3, P = 0.05). The CFS-MAX achieved 98 +/- 11% of predicted VO2 max. The CFS group had a higher RPE at the same absolute workloads as controls (P < 0.01) but not the same relative workloads. CONCLUSION Compared with normal controls, women with CFS have an aerobic power indicating a low normal fitness level with no indication of cardiopulmonary abnormality. Our CFS group could withstand a maximal treadmill exercise test without a major exacerbation in either fatigue or other symptoms of their illness.

Persistent stress-induced sensitization of adrenocortical and startle responses

We assessed the functional adrenocortical and behavioral state of rats previously exposed to repeated stressor presentations. In Experiment 1, the whole-body startle response to threshold (91 dB) and suprathreshold (96 dB) stimuli was assessed in rats given 3 daily sessions (3DS) of 40, 2-mA tailshocks. The 3DS rats showed an exaggerated startle response to the threshold auditory stimulus 4 days poststressor compared to nonshocked controls (CON). An exaggerated startle response in stressed rats was not evident either 1 day or 10 days poststressor. In Experiment 2, adrenocortical sensitization and behavioral reactivity were assessed in rats exposed to 1 day (1DS) or 3 days of our stress regimen. Stressed rats exhibited elevated basal plasma corticosterone (CORT) levels 1 day poststressor which recovered by 9 days poststressor. Stressed rats also exhibited suppressed open-field activity 4 days poststressor. On the 10th day poststressor, rats were exposed to a single tailshock. The 1DS and 3DS rats showed both a sensitized and prolonged CORT response to stressor reexposure compared to control rats which received only the single tailshock. In addition, on the 11th day poststressor 3DS rats exhibited a moderate recapitulation of the elevated basal CORT levels seen after the initial stressor exposures. Thus, exposure to our stress regimen produces a chronic stress state in rats characterized by persistent behavioral and adrenocortical sensitization, as well as suppressed open-field activity and elevated basal CORT levels. Rats exhibiting a chronic stress state may be appropriate as a model for the study of stress-related psychophysiological illnesses, such as posttraumatic stress disorder.

Vagal tone is reduced during paced breathing in patients with the chronic fatigue syndrome

Patients with chronic fatigue syndrome (CFS) often complain of an inability to maintain activity levels and a variety of autonomic-like symptoms that make everyday activiry intolerable at times. The purpose of the study was to determine if there were differences in vagal activiry at fixed breathing rates in women with CFS. Twelve women with the diagnosis of CFS between the ages of 32 and 59 years volunteered for the study. Healthy women, who were between the ages of 30 and 49, served as controls. Full signal electrocardiograph and respiratory signals were collected during a paced breathing protocol of three fixed breathing rates (8, 12 and 18 breaths/min) performed in the sitting and standing postures. Vagal activity was analyzed by means of heart rate spectral analysis to determine the subjects response to specific breathing rates and postures. Heart rate variability was used as a non-invasive method of measuring the parasympathetic component of the autonomic nervous system. Using this method, although there was significantly less vagal power in the sitting versus the standing postures for both groups, the overall vagal power was significantly lower (p < 0.034) in the CFS group versus healthy controls. Vagal power was also significantly lower (p < 0.01 to p < 0.05) at all breathing rates in both postures except while standing and breathing at 18 breaths/min. Knowledge of the differences in vagal activity for CFS patients may allow stratification for the analysis of other research variables.

Immunologic parameters in chronic fatigue syndrome, major depression, and multiple sclerosis

The purpose of this study was to evaluate the immune dysfunction hypothesis of chronic fatigue syndrome (CFS) by comparing immunologic data from patients with CFS with data from patients with other fatiguing illnesses--major depression and multiple sclerosis (MS)--and with data from healthy sedentary controls. The subjects were 65 healthy sedentary controls, 71 CFS patients (41 with no axis-I diagnosis), 23 patients with mild MS, and 21 patients with major depression. Blood was sampled and assayed for the following: (1) immunologic serologic variables--circulating immune complexes (i.e., Raji cell and C1q binding), immunoglobulins A, E, G, and M, and IgG subclasses; (2) cell surface activation markers--the proportion of CD4+ cells expressing CD45RA+ and CD45RO+ and the proportion of CD8+ cells expressing CD38+, CD11b-, HLA-DR+ and CD28+; and (3) natural killer (NK) total cell count as well as the proportion of lymphocytes expressing NK cell surface markers (i.e., CD3-/CD16+ and CD56+. Of the 18 variables studied, differences between CFS patients and controls were found only for IgG1 and IgG3. When CFS patients were stratified by the presence or absence of concurrent axis-I disease, it was the group with axis-I disorder that had the lowest IgG1 values-contrary to expectation. When data from patients with MS and major depression were also evaluated, the subclass deficiency was no longer significant. The one group to show evidence for immune activation (i.e., an elevated proportion of CD4+ cells expressing the CD45RA+ activation marker) was the group with mild MS. These data support neither immune dysfunction nor immune activation in CFS or in major depression, for the variables studied. The reductions in IgG subclasses may be an epiphenomenon of patient or control subject composition. In contrast, MS, even in the mild and early stages, as in the patients studied here, is associated with immune activation.

Single-Blind, Placebo Phase-in Trial of Two Escalating Doses of Selegiline in the Chronic Fatigue Syndrome

Aim: To perform a clinical trial of selegiline in 25 patients with chronic fatigue syndrome (CFS) where patients were told they would receive placebo or active agent at different times during the 6-week trial. We chose selegiline, a specific monoamine oxidase (MAO) B receptor inhibitor, because a prior trial of low-dose phenelzine, a nonspecific MAO inhibitor, showed a small but significant therapeutic effect. Methods: Questionnaires comprised of 19 tests of mood, fatigue, functional status and symptom severity were collected at the start and end of the trial as well as 2 weeks after its start. The trial was done in three 2-week blocks: in the first, 2 placebo pills were given per day; in the next, one 5-mg tablet of agent and one placebo were given per day, and in the last, a 5-mg tablet of agent was given twice a day. The plan was to compare the changes in the 19 tests during the placebo phase to those found in the active treatment phase in 19 patients completing the trial. Findings: Significant improvement in 3 variables – tension/anxiety, vigor and sexual relations – was found. A significant pattern of improvement compared to worsening was found for the 19 self-report vehicles during active treatment as compared with placebo treatment. Evidence for an antidepressant effect of the drug was not found. Conclusions: Selegiline has a small but significant therapeutic effect in CFS which appears independent of an antidepressant effect.

Short-term predictive changes in the dynamics of disparity vergence eye movements.

Repetitive stimulation of the disparity vergence system to large convergent step stimuli has been shown to increase the dynamics of subsequent responses to smaller step stimuli. Here we show that decreases in the dynamics of both disparity convergence and divergence eye movements can be induced using a frequently occurring small amplitude conditioning stimulus to modify responses to a larger, occasionally presented test stimulus. In one experiment, a simple conditioning stimulus consisting of repetitive 1 degrees step stimuli was used to modify the dynamic vergence response to an occasional 4 degrees step test stimulus. An experimental trial consisted of three phases: baseline, conditioning, and recovery. The baseline and recovery phases used only the 4 degrees test stimuli. The dynamic characteristics of the responses to test stimuli were quantified by measuring the magnitude of the peak velocity. A statistically significant change was observed between the dynamics of conditioned responses compared to baseline and recovery responses indicting modification by the conditioning stimuli. During recovery, the response dynamics returned to levels near baseline levels showing that the decrease in response dynamics was caused by the conditioning stimulus, not fatigue. Another experiment showed that the response dynamics to large stimuli could be decreased whereas the dynamics of small stimuli could be increased by the same intermediate conditioning stimulus. Other experiments suggest that the modifications are due to a predictive mechanism. The results indicate that the dynamics of disparity vergence eye movements are malleable and depend to some extent on the amplitude of preceding stimuli.

Facilitated acquisition of the classically conditioned eyeblink response in women taking oral contraceptives.

Although anecdotal reports suggest that associative learning processes are affected by menstrual phase, empirical evidence has been equivocal. Moreover, there is a dearth of research concerning fluctuations of artificial or exogenous female hormones on learning and memory. Therefore, in this preliminary study we assessed learning in women who take oral contraceptives and those who do not during the three phases of the menstrual cycle: early, middle, and later cycle. The behavioral assessment included short-trace eyeblink conditioning, acoustic startle reactivity, and a fine motor coordination task (grooved pegboard). Oral contraceptive users generally acquired the conditioned eyeblink response better than non-users. Similar enhancements were observed for fine motor coordination and startle responsiveness. Further research will need to distinguish whether the hormone influence is upon the associative processes or the sensory-motor pathways involved in nonassociative learning.

Cardiovascular Evaluation of Electronic Control Device Exposure in Law Enforcement Trainees: A Multisite Study

Objective: Occupational health risk with regard to training exercises is a relatively under studied domain for law enforcement officers. One potential health risk is exposure to electronic control devices (ECDs). Methods: Seven different training facilities in six states participated. Law enforcement trainees (N = 118) were exposed to Taser Internationals (Scottsdale, AZ) X26® for up to 5 seconds. Results: There was no evidence of cardiac or skeletal muscle breakdown. Exposure did not adversely affect electrocardiogram (ECG) morphology obtained 24 hours after exposure in 99 trainees. For two trainees with preexisting ECG abnormalities, ECG morphology differed in the post-ECD samples. Conclusions: The results from this large, multisite study suggest that, for most trainees, ECD exposure does not represent a significant health risk. Further investigation is warranted for cardiac vulnerability and potential interactions with ECD exposure.

Impaired associative learning in chronic fatigue syndrome

PATIENTS with chronic fatigue syndrome (CFS) report cognitive difficulties (impaired attention, memory and reasoning). Neuropsychological tests have failed to consistently find cognitive impairments to the degree reported by CFS patients. We tested patients with CFS and sedentary controls in protocols designed to measure sensory reactivity and acquisition of the classically conditioned eyeblink response. Patients with CFS exhibited normal sensitivity and responsivity to acoustic stimuli. However, CFS patients displayed impaired acquisition of the eyeblink response using a delayed-type conditioning paradigm. Sensitivity and responsivity to the airpuff stimulus were normal. In the absence of sensory/motor abnormalities, impaired acquisition of the classically conditioned eyeblink response indicates an associative deficit. These data suggest organic brain dysfunction within a defined neural substrate in CFS patients.

Respiratory and Cardiovascular Response during Electronic Control Device Exposure in Law Enforcement Trainees

Objective: Law enforcement represents a large population of workers who may be exposed to electronic control devices (ECDs). Little is known about the potential effect of exposure to these devices on respiration or cardiovascular response during current discharge. Methods: Participants (N = 23) were trainees exposed to 5 s of an ECD (Taser X26®) as a component of training. Trainees were asked to volitionally inhale during exposure. Respiratory recordings involved a continuous waveform recorded throughout the session including during the exposure period. Heart rate was calculated from a continuous pulse oximetry recording. Results: The exposure period resulted in the cessation of normal breathing patterns in all participants and in particular a decrease in inspiratory activity. No significant changes in heart rate during ECD exposure were found. Conclusion: This is the first study to examine breathing patterns during ECD exposure with the resolution to detect changes over this discrete period of time. In contrast to reports suggesting respiration is unaffected by ECDs, present evidence suggests that voluntary inspiration is severely compromised. There is no evidence of cardiac disruption during ECD exposure.