Daniel E. Vigo

Heart rate variability response to mental arithmetic stress in patients with schizophrenia: Autonomic response to stress in schizophrenia

BACKGROUNDnThe vulnerability-stress hypothesis is an established model of schizophrenia symptom formation. We sought to characterise the pattern of the cardiac autonomic response to mental arithmetic stress in patients with stable schizophrenia.nnnMETHODSnWe performed heart rate variability (HRV) analysis on recordings obtained before, during, and after a standard test of autonomic function involving mental stress in 25 patients with DSM-IV schizophrenia (S) and 25 healthy individuals (C).nnnRESULTSnPatients with schizophrenia had a normal response to the mental arithmetic stress test. Relative contributions of low-frequency (LF) HRV and high-frequency (HF) HRV influences on heart rate in patients were similar to controls both at rest (LF 64+/-19% (S) vs. 56+/-16% (C); HF 36+/-19% (S) vs. 44+/-16% (C), t=1.52, p=0.136) and during mental stress, with increased LF (S: 76+/-12%, C: 74+/-11%) and decreased HF (S: 24+/-12%, C: 26+/-11%) in the latter study condition. Whilst healthy persons recovered the resting pattern of HRV immediately after stress termination (LF 60+/-15%, HF 40+/-15%, F=18.5, p<0.001), in patients HRV remained unchanged throughout the observed recovery period, with larger LF (71+/-17%) and lower HF (29+/-17%) compared with baseline (F=7.3, p=0.013).nnnCONCLUSIONSnPatients with schizophrenia exhibit a normal response to the mental arithmetic stress test as a standard test of autonomic function but in contrast with healthy individuals, they maintain stress-related changes of cardiac autonomic function beyond stimulus cessation.

Heart rate variability response to mental arithmetic stress is abnormal in first-degree relatives of individuals with schizophrenia.

BACKGROUNDnSchizophrenia patients exhibit an abnormal autonomic response to mental stress. We sought to determine the cardiac autonomic response to mental arithmetic stress in their unaffected first-degree relatives.nnnMETHODSnHeart rate variability (HRV) analysis was performed on recordings obtained before, during, and after a standard mental arithmetic task to induce mental stress. 22 unaffected first-degree relatives of patients meeting DSM-IV criteria for schizophrenia (R) and 22 healthy individuals (C) were included in this study.nnnRESULTSnPatients relatives (R) had a normal response to the mental arithmetic stress test, showing an increased heart rate compared with controls. They also displayed the characteristic pattern of relative contributions of HRV components that consists of increased low-frequency (LF) HRV and decreased high-frequency (HF) HRV. Recovery of the resting pattern of HRV immediately after stress termination was observed in healthy subjects (LF 62+/-16% vs. 74+/-10% , HF 37+/-16% vs. 25+/-10%, F=9.616, p=0.004), but not in patients relatives (LF 60+/-19% vs. 70+/-13%, HF 40+/-19% vs. 29+/-13%, F=8.4, p=0.056).nnnCONCLUSIONSnFirst-degree relatives of schizophrenia patients exhibit an abnormal pattern of protracted response to mental arithmetic stress, though less intense than that observed in patients in a previous study. This suggests that a pattern of autonomic response to stress may therefore be familial and heritable.

Wavelet transform shows age-related changes of heart rate variability within independent frequency components

Reduction in overall heart rate variability (HRV) associated with aging is determined by a decreased amplitude of heart rate oscillations at all frequency levels, including high frequency (HF) oscillations attributed to respiratory sinus arrhythmia, low frequency (LF) oscillations attributed to Meyer waves and very low frequency (VLF) oscillations of an uncertain origin, presumably linked among others to thermoregulation. However, no studies were conducted to determine whether heart rate oscillations at independent frequency levels show themselves reduced HRV. Wavelet transform was applied to filter specific frequency components of HRV in a sample of younger (21-34 years old) and older (68-85 years old) healthy subjects. HRV indexes were measured within HF, LF and VLF components. The standard deviation of all RR intervals (SDNN) and the square root of the mean squared differences of successive RR intervals (RMSSD) were used as conventional linear time-domain measures. Sample entropy (SampEn) was used as a measure of nonlinear variability. Aged subjects showed lower SDNN at VLF (p < 0.001), LF (p = 0.007) and HF (p < 0.001). Lower RMSSD was observed in older people at VLF (p < 0.001), LF (p = 0.005) and HF (p < 0.001). SampEn was reduced by aging only at VLF level (p < 0.001). In aged people, linear variability was diminished within all frequency components, while nonlinear variability was lower only at VLF level. Preserved central, nonreflex autonomic modulation over the baroreflex control and the central cardiopulmonary coupling might explain this observation. Potential applications of this method include the study of heart rate regulation during sleep in which a complex interaction between the sympathetic and the parasympathetic activity takes place.

Circadian analysis of myocardial infarction incidence in an Argentine and Uruguayan population

BackgroundThe occurrence of variations in the spectrum of cardiovascular disease between different regions of the world and ethnic groups have been the subject of great interest. This study report the 24-h variation of myocardial infarction (MI) occurrence in patients recruited from CCU located in Argentina and Uruguay.MethodsA cohort of 1063 patients admitted to the CCU within 24 h of the onset of symptoms of an acute MI was examined. MI incidence along the day was computed in 1 h-intervals.ResultsA minimal MI incidence between 03:00 and 07:00 h and the occurrence of a first maximum between 08:00 and 12:00 h and a second maximum between 15:00 and 22:00 h were verified. The best fit curve was a 24 h cosinor (acrophase ~ 19:00 h, accounting for 63 % of variance) together with a symmetrical gaussian bell (maximum at ~ 10:00 h, accounting for 37 % of variance). A similar picture was observed for MI frequencies among different excluding subgroups (older or younger than 70 years; with or without previous symptoms; diabetics or non diabetics; Q wave- or non-Q wave-type MI; anterior or inferior MI location). Proportion between cosinor and gaussian probabilities was maintained among most subgroups except for older patients who had more MI at the afternoon and patients with previous symptoms who were equally distributed among the morning and afternoon maxima.ConclusionThe results support the existence of two maxima (at morning and afternoon hours) in MI incidence in the Argentine and Uruguayan population.

Nonlinear analysis of heart rate variability within independent frequency components during the sleep-wake cycle

Heart rate variability (HRV) is a complex signal that results from the contribution of different sources of oscillation related to the autonomic nervous system activity. Although linear analysis of HRV has been applied to sleep studies, the nonlinear dynamics of HRV underlying frequency components during sleep is less known. We conducted a study to evaluate nonlinear HRV within independent frequency components in wake status, slow-wave sleep (SWS, stages III or IV of non-rapid eye movement sleep), and rapid-eye-movement sleep (REM). The sample included 10 healthy adults. Polysomnography was performed to detect sleep stages. HRV was studied globally during each phase and then very low frequency (VLF), low frequency (LF) and high frequency (HF) components were separated by means of the wavelet transform algorithm. HRV nonlinear dynamics was estimated with sample entropy (SampEn). A higher SampEn was found when analyzing global variability (Wake: 1.53+/-0.28, SWS: 1.76+/-0.32, REM: 1.45+/-0.19, p=0.005) and VLF variability (Wake: 0.13+/-0.03, SWS: 0.19+/-0.03, REM: 0.14+/-0.03, p<0.001) at SWS. REM was similar to wake status regarding nonlinear HRV. We propose nonlinear HRV is a useful index of the autonomic activity that characterizes the different sleep-wake cycle stages.

Depressive symptoms are related to decreased low-frequency heart rate variability in older adults with decompensated heart failure.

Background/Aims: Depression has been associated with increased mortality among individuals with heart failure, but the mechanism for this association is unsettled. Depression is often found to result in autonomic dysfunction which, if present in heart failure, might help explain worsened outcomes. Methods: This study was a cross-sectional evaluation of the relationship between depressive symptoms and cardiac autonomic function, as assessed by short-term heart rate variability (HRV) analysis in aged patients with acute/decompensated heart failure of coronary origin (CHF). A 21-item Hamilton Depression score and measures of short-term HRV were obtained in 31 inpatients ≧65 years of age, 24–72 h after admission to the coronary care unit with a diagnosis of CHF. Results: Clinical depression was present in 22.6% of participants. In the sample as a whole, increasing depressive symptoms were associated with decreased low-frequency HRV. Conclusion: These results may be important in light of recent indications that decreased low-frequency HRV is a predictor of mortality in patients with heart failure.

Nonlinear analysis of heart rate variability in patients with eating disorders

Patients with anorexia nervosa or bulimia nervosa often have signs of autonomic dysfunction potentially deleterious to the heart. The aim of this study was to ascertain the nonlinear properties of heart rate variability in patients with eating disorders. A group of 33 women with eating disorders (14 anorexia, 19 bulimia) and 19 healthy controls were included in the study. Conventional time- and frequency-domain heart rate variability measurements, along with nonlinear heart rate variability measurements including the short-term fractal scaling exponent α and approximate entropy (ApEn) were calculated. Anorexia nervosa patients exhibited decreased values of α, while bulimia nervosa patients had decreased values of ApEn. Low-frequency heart rate variability was decreased in patients with anorexia. In conclusion, these results are compatible with the view that a more severe alteration of cardiac autonomic function is present in anorexia than in bulimia.

Assessing the efficacy of melatonin to curtail benzodiazepine/Z drug abuse

The abuse of benzodiazepine (BZP) and Z drugs has become, due to the tolerance and dependence they produce, a serious public health problem. Thirty years ago, we demonstrated in experimental animals the interaction of melatonin with central BZD receptors, and in 1997 we published the first series of elderly patients who reduced BZP consumption after melatonin treatment. Almost every single neuron in the hypothalamic suprachiasmatic nuclei (SCN), the central pacemaker of the circadian system, contains γ-aminobutyric acid (GABA) and many results in animals point out to a melatonin interaction with GABA-containing neurons. In addition, central-type BZD antagonism, that obliterates GABAA receptor function, blunted most behavioral effects of melatonin including sleep. Melatonin is involved in the regulation of human sleep. This is supported by the temporal relationship between the rise of plasma melatonin levels and sleep propensity as well as by the sleep-promoting effects of exogenously administered melatonin. Both meta-analyses and consensus agreements give support to the therapeutic use of melatonin in sleep disorders. This action is attributed to MT1 and MT2 melatoninergic receptors localized in the SCN, as well as in other brain areas. This review discusses available data on the efficacy of melatonin to curtail chronic BZD/Z drug use in insomnia patients. A major advantage is that melatonin has a very safe profile, it is usually remarkably well tolerated and, in some studies, it has been administered to patients at very large doses and for long periods of time, without any potentiality of abuse. Further studies on this application of melatonin are warranted.

Melatonin, mitochondria, and the metabolic syndrome

A number of risk factors for cardiovascular disease including hyperinsulinemia, glucose intolerance, dyslipidemia, obesity, and elevated blood pressure are collectively known as metabolic syndrome (MS). Since mitochondrial activity is modulated by the availability of energy in cells, the disruption of key regulators of metabolism in MS not only affects the activity of mitochondria but also their dynamics and turnover. Therefore, a link of MS with mitochondrial dysfunction has been suspected since long. As a chronobiotic/cytoprotective agent, melatonin has a special place in prevention and treatment of MS. Melatonin levels are reduced in diseases associated with insulin resistance like MS. Melatonin improves sleep efficiency and has antioxidant and anti-inflammatory properties, partly for its role as a metabolic regulator and mitochondrial protector. We discuss in the present review the several cytoprotective melatonin actions that attenuate inflammatory responses in MS. The clinical data that support the potential therapeutical value of melatonin in human MS are reviewed.

Relationship between Cognitive and Sleep–wake Variables in Asymptomatic Offspring of Patients with Late-onset Alzheimer’s Disease

Early neuropathological changes characteristic of late-onset Alzheimer’s disease (LOAD) involve brain stem and limbic structures that regulate neurovegetative functions, including sleep–wake rhythm. Indeed, sleep pattern is an emerging biomarker and a potential pathophysiological mechanism in LOAD. We hypothesized that cognitively asymptomatic, middle-aged offspring of patients with LOAD (O-LOAD) would display a series of circadian rhythm abnormalities prior to the onset of objective cognitive alterations. We tested 31 children of patients with LOAD (O-LOAD) and 19 healthy individuals without family history of Alzheimer’s disease (control subjects, CS) with basic tests of cognitive function, as well as actigraphy measures of sleep–wake rhythm, cardiac autonomic function, and bodily temperature. Unexpectedly, O-LOAD displayed subtle but significant deficits in verbal episodic memory (Rey Auditory Verbal Learning Test delayed recall 10.6 ± 0.4 vs. 8.6 ± 0.6, t = 4.97, df = 49, p < 0.01) and language (Weschler’s vocabulary 51.4 ± 1.3 vs. 44.3 ± 1.5, t = 2.49, df = 49, p < 0.001) compared to CS, even though all participants had results within the clinically normal range. O-LOAD showed a phase-delayed rhythm of body temperature (2.56 ± 0.47 h vs. 3.8 ± 0.26 h, t = 2.48, df = 40, p = 0.031). Cognitive performance in O-LOAD was associated with a series of cardiac autonomic sleep–wake variables; specifically indicators of greater sympathetic activity at night were related to poorer cognition. The present results suggest sleep pattern deserves further study as a potential neurobiological signature in LOAD, even in middle-aged, at risk individuals.