Worsening of depressive symptoms 6 months after an acute coronary event in older adults is associated with impairment of cardiac autonomic function

Background: Depression increases mortality of coronary patients, and autonomic dysfunction has been proposed as an explanation for this association. Methods: In a sample of 38 adults ≥ 60 years with myocardial infarction or unstable angina, we studied depression (presence of a major depressive episode and 21-item Hamilton depression score) and heart rate variability (HRV) of 550 normal beats shortly after admission to the coronary care unit (CCU). Thirty patients were alive at 6 months and were studied at that time as well. Spectral HRV measurements included power in the high-frequency range (HF, 0.15—0.55 Hz, a measure of parasympathetic activity) and low-frequency range (LF, 0.03—0.15 Hz). Nonspectral HRV measurements included standard deviation of normal beats (SDNN) and two measures of vagal activity: percentage of adjacent cycles differing by >50 ms (pNN50) and the root-mean-square of differences in successive beats (rMSNN). Results: Patients who died within 6 months (n=8) had a higher Hamilton-D score than survivors (13.9±6.5 vs. 18.4±5.6, P=0.039) and were more likely to have an episode of major depression upon admission to the CCU (71 vs. 27%, P=0.027). An increase in Hamilton-D score at 6 months correlated with a decrease in total (r=–0.48, P=0.014), high-frequency (r=–0.49, P=0.007), and low-frequency HRV (r=–0.46, P=0.014). Limitations: Patients belonged to a single institution and there was a small proportion of men. Conclusions: Progression of mood symptoms 6 months after an acute coronary event is associated with an impairment of autonomic control of the heart in elderly individuals.     

QT Interval Prolongation in Future SIDS Victims: A Polysomnographic Study

Objective:

Previous data have suggested that a prolonged QTc interval during the first days of life can be associated with some cases of sudden infant death syndrome (SIDS). Analysis of heart rate variability during sleep in future SIDS victims has shown findings compatible with an imbalance in autonomic tone. We hypothesized that some future SIDS infants could have longer QTc intervals during sleep, compared with healthy control infants, and that this difference would correlate with the autonomic imbalance already found in these infants.

Methods:

QTc intervals and a heart rate autoregressive power spectral analysis were calculated during the same periods in the polysomnographic sleep recordings of 18 infants who eventually died of SIDS and of 18 control infants. The control infants were matched for sex, gestational age, postnatal age, birth weight, and sleep position. The median postnatal age was 8 weeks.

Results:

Compared with control infants, future SIDS victims were characterized by having longer QTc intervals during total sleep (P = 0.019), rapid eye movement sleep (P = 0.045) and non-rapid eye movement sleep (P = 0.029). When the night was divided into 3 equal parts, this difference was always present but was most marked during the last part of the night. There was, respectively, a negative and a positive correlation between parasympathetic activity and sympathovagal balance and median and maximum QTc interval values.

Conclusion:

Compared with QTc intervals in matched control infants, QTc intervals were increased in future SIDS victims. Such a prolongation could be related to the autonomic dysfunction already reported in these patients.

Citation:

Franco P; Groswasser J; Scaillet S; Lanquart JP; Benatar A; Sastre JP; Chevalier P; Kugener B; Kahn A; Lin JS. QT interval prolongation in future SIDS victims: a polysomnographic study. SLEEP 2008;31(12):1691–1699.     

The effect of major depression on postexercise cardiovascular recovery

Major depressive disorder (MDD) is associated with increased cardiovascular (CV) mortality. Dysfunctional autonomic control of the CV system may represent a mechanism explaining this relationship. Poor CV recovery after exercise, indicative of dysfunctional autonomic control of the CV system, predicts CV events and death. This is the first study to examine the association between MDD and postexercise CV recovery. Some 886 patients underwent exercise stress tests. Heart rate (HR), systolic blood pressure, and diastolic blood pressure were measured at rest, peak exercise, 1 min, and 5 min after exercise. Patients with MDD had slower HR recovery (p=.026) 1 min after exercise than non-MDD patients. No other effects of MDD were found. MDD is accompanied by a dysregulation in autonomic control of exercise-related CV recovery, suggesting that depressed individuals have a slow parasympathetic recovery from exercise.     

肝内胆汁淤积症孕鼠的胎鼠心率功率谱变化与猝死的关系

应用皮下注射雌、孕激素建立妊娠肝内胆汁淤积(ICP)大鼠模型,通过Powerlab生物信号处理系统Chart5软件引导妊娠第21d胎鼠宫内心电图,分析胎鼠心率变异性(HRV)频域指标低频带(LF)、高频带(HF)及LF/HF值,探讨肝内胆汁淤积症孕鼠的胎鼠心脏自主神经系统变化与猝死的关系。结果显示,(1)ICP模型组孕鼠血清总胆汁酸水平为(78.5±4.5)μmol/L,正常对照组为(24.6±3.6)μmol/L,两组差异有极显著性;P<0.01;(2)ICP模型组实验开始时胎鼠心电图显示正常,持续观察29.3±6.4min后出现胎鼠心律不齐,继续观察23.5±4.6min后胎鼠死亡,而正常对照组持续观察90min,胎鼠心电图均显示正常;(3)ICP模型组胎鼠出现心律失常前20min内HRV频域指标LF和LF/HF分别为48.45±4.11nu和0.99±0.14,高于正常对照组胎鼠33.87±4.31nu和0.61±0.10,两组差异均有显著性,均为P<0.01;(4)ICP模型组胎鼠猝死前15min内LF及LF/HF随着死亡时间的濒临而呈进行性上升趋势。研究表明,孕鼠肝内胆汁淤积症时胎鼠死亡前出现短暂的心律失常阶段;ICP孕鼠的胎鼠猝死可能与高水平胆汁酸诱导胎鼠心脏自主神经活动失衡有关;HRV分析技术对于胎儿宫内安危的监护将会有很好的应用前景。     

Denaturing high-performance liquid chromatography screening of the long QT syndrome-related cardiac sodium and potassium channel genes and identification of novel mutations and single nucleotide polymorphisms

Mutations in cardiac potassium and sodium channel genes are responsible for several hereditary cardiac arrhythmia syndromes. We established a denaturing high-performance liquid chromatography (DHPLC) protocol for rapid mutation screening of these genes, and reported mutations and variations identified by this method. We included 28 patients with Brugada syndrome, 4 with congenital long QT syndrome (LQTS), 11 with drug-induced LQTS, 4 with idiopathic ventricular fibrillation, and 50 normal volunteers. Polymerase chain reactions were performed to amplify the entire coding region of these genes. DHPLC was used to screen for heteroduplexes then DNA sequencing was performed. With this method, we identified the mutation(s) in all four patients with congenital LQTS (KCNQ1 A341V, KCNH2 N633D, KCNH2 2768Cdel and KCNE1 K70 N Y81C double mutations). We also identified the SCN5A A551T mutation in 1 of the 28 patients with Brugada syndrome. All the above-mentioned mutations were novel except KCNQ1 A341V. No mutations were identified in patients with drug-induced LQTS or idiopathic ventricular fibrillation. In total, 25 single nucleotide polymorphisms were identified, 10 of which were novel. In conclusion, DHPLC is a sensitive and rapid method for detection of cardiac sodium and potassium channel gene mutations.     

Neuritis cordis due to the acute polyneuritis of the Guillain-Barré syndrome

Summary Three patients with the Guillain-Barré syndrome which followed the course of Landry's acute ascending paralysis died a sudden cardiac death. Autonomic dysfunction had appeared clinically, consisting of sphincter disturbances in one patient and fluctuating blood pressure and bradycardia in the other. In a twenty-three year old female patient cardiac function had been inconspicuous, apart from tachycardia, but the ECG showed S-T segment depression and flat T waves. Postmortem examination revealed acute inflammatory demyelinating polyradiculoneuritis involving the peripheral autonomic nervous system and especially the nerves of the heart. Immunohistochemically, the inflammatory cell infiltrations of this neuritis cordis consisted of macrophages (MAC 387 positive) and T lymphocytes (UCHL1 positive). No indication of a direct viral infection of the inflamed cardiac nerves was detectable by immunohistochemistry (HSV, CMV, influenza virus) nor by electron microscopy. The neuritis cordis was classified as an inflammatory cardioneuropathy secondary to a patchy acute polyneuritis of the Guillain-Barré syndrome, involving the autonomic nervous system. Myocarditis could be discounted, and the neuritis cordis was thought to be responsible for the sudden cardiac death.Dedicated to Professor Dr.med. Otto StochdorphPresented in part at 71. Jahrestagung der Deutschen Gesellschaft für Pathologie, Salzburg, Juni 1987     

Heart rate turbulence analysis in female patients with fibromyalgia

OBJECTIVE:Fibromyalgia is characterized by diffuse musculoskeletal pain and discomfort. There are several reports regarding autonomic nervous system dysfunction in patients with fibromyalgia. Heart rate turbulence is expressed as ventriculophasic sinus arrhythmia and has been considered to reflect cardiac autonomic activity. Heart rate turbulence has been shown to be an independent and powerful predictor of sudden cardiac death in various cardiac abnormalities. The aim of this study is to determine whether heart rate turbulence is changed in female patients with fibromyalgia compared with healthy controls.METHODS:Thirty-seven female patients (mean age, 40±11 years) with fibromyalgia, and 35 age- and sex-matched healthy female control subjects (mean age, 42±9 years) were included. Twenty-four hours of ambulatory electrocardiography recordings were collected for all subjects, and turbulence onset and turbulence slope values were automatically calculated.RESULTS:The baseline clinical characteristics of the two groups were similar. There were no significant differences in turbulence onset and turbulence slope measures between patients and control subjects (turbulence onset: −1.648±1.568% vs. −1.582±1.436%, p ϝ 0.853; turbulence slope: 12.933±5.693 ms/RR vs. 13.639±2.505 ms/RR, p ϝ 0.508). Although body mass index was negatively correlated with turbulence slope (r ϝ −0.258, p ϝ 0.046), no significant correlation was found between body mass index and turbulence onset (r ϝ 0.228, p ϝ 0.054).CONCLUSION:To the best of our knowledge, this is the first study to evaluate heart rate turbulence in patients with fibromyalgia. It appears that heart rate turbulence parameters reflecting cardiac autonomic activity are not changed in female patients with fibromyalgia.     

Cognitive function in adults with type 2 diabetes and major depression

The aim of this study was to identify characteristics of neuropsychological functioning among type 2 diabetic adults with and without major depression. Twenty type 2 diabetics with major depression, 20 non-depressed type 2 diabetics and 34 controls without diabetes or depression were compared. A mixed effects repeated measures analysis of covariance indicated significant differences in overall cognitive functioning between diagnostic groups, specifically depressed diabetics demonstrated greater cognitive dysfunction than controls. Further comparisons indicated that depressed diabetics performed significantly worse than non-depressed diabetics in attention/information processing speed. Relative to controls, depressed diabetics performed significantly worse in attention/information processing speed and executive functioning, while there was a trend for non-depressed diabetics to perform worse in executive functioning. These findings suggest that depression negatively impacts cognitive performance among adults with type 2 diabetes, which may have implications for neural circuitry underlying cognitive and mood changes in diabetic patients.     

Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long QT syndrome

Long QT syndrome (LQTS) is a rare and clinically heterogeneous inherited disorder characterized by a long QT interval on the electrocardiogram, increased risk of syncope and sudden death caused by arrhythmias. This syndrome is mostly caused by mutations in genes encoding various cardiac ion channels. The clinical heterogeneity is usually attributed to variable penetrance. One of the reasons for this variability in expression could be the coexistence of common single nucleotide polymorphisms (SNPs) on LQTS-causing genes and/or unknown genes. Some synonymous and nonsynonymous exonic SNPs identified in LQTS-causing genes may have an effect on the cardiac repolarization process and modulate the clinical expression of a latent LQTS pathogenic mutation. We report the molecular pattern of 44 unrelated patients with LQTS using denaturing high-performance liquid chromatography analysis of the KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2 genes. Forty-five disease-causing mutations (including 24 novel ones) were identified in this cohort. Most of our patients (84%) showed complex molecular pattern with one mutation (and even two for four patients) associated with several SNPs located in several LQTS genes.     

VEGF plasma level variations in duloxetine-treated patients with major depression

Background

The vascular endothelial growth factor (VEGF) signaling, which modulates angiogenesis and neurogenesis within the neurovascular unit, might play an important role in the neuro-endocrine-immune (NEI) stress-adaptation system. Recent evidence suggests that VEGF is involved in the pathophysiology of a number of diseases including major depressive disorder (MDD) and is affected by some treatments, including antidepressants. The objective of the study was to investigate the VEGF level variations in MDD patients during antidepressant treatment with duloxetine, a relatively new SNRI.

Methods

A total of 30 MDD patients and 32 healthy controls were assessed using the Hamilton Depression Scale (HAM-D) and monitored for VEGF plasma levels at baseline, week 6 and week 12 of duloxetine treatment (60 mg/day) and at baseline, respectively.

Results

According to early clinical response to duloxetine (defined at week 6 by reduction>50% of baseline HAM-D score), the MDD patients were divided into early responders (ER) and early non-responders (ENR). During duloxetine treatment, we found an opposite trend in the VEGF levels between ER and ENR: in ER the VEGF levels significantly increased in association with clinical response at W6, while in ENR the VEGF levels significantly decreased in association with an overall clinical response at W12.

Limitations

Small sample size.

Conclusions

The opposite trends in VEGF levels, increasing in ER and decreasing in ENR, might reflect differential Norepinephrine/Serotonin effects of duloxetine on differential neurobiological backgrounds of depressive syndromes. Overall, the modulation of VEGF signaling within the neurovascular unit during antidepressant treatment could hypothetically favor the remodeling of neural circuitry, contributing to adaptive adjustment of the NEI stress-adaptation system.     

Opipramol in the climacteric syndrome. A double-blind, placebo-controlled trial

In a double-blind trial, 48 women suffering from post-menopausal complaints were randomly allocated to an 8-wk course of treatment with opipramol (50 mg sugar-coated tablets) or an identical placebo. Autonomic nervous system instability (7 target symptoms) and depression (10 target symptoms) were scored at the beginning of the trial and after 1, 2, 4, 6 and 8 wk and a final assessment was made at the end of the trial. A daily record of hot flushes was kept by the patients. Opipramol brought about an approximately 50% reduction in the symptoms, but a considerable placebo effect was noticed also. It was found that opipramol treatment was significantly better than placebo treatment (P less than 0.01) in reducing hot flushes after 2 mth of therapy. The symptoms of depression were significantly reduced in the opipramol group, as compared with the placebo group. No significant reduction could be seen in the vasomotor symptoms. The final assessment at the end of the trial period showed a significant difference (P less than 0.05) in favour of opipramol.     

Exposure to light at night and risk of depression in the elderly

Background

Recent advances in understanding the fundamental links between chronobiology and depressive disorders have enabled exploring novel risk factors for depression in the field of biological rhythms. Increased exposure to light at night (LAN) is common in modern life, and LAN exposure is associated with circadian misalignment. However, whether LAN exposure in home settings is associated with depression remains unclear.

Methods

We measured the intensities of nighttime bedroom light and ambulatory daytime light along with overnight urinary melatonin excretion (UME) in 516 elderly individuals (mean age, 72.8). Depressive symptoms were assessed using the Geriatric Depression Scale.

Results

The median nighttime light intensity was 0.8 lx (interquartile range, 0.2–3.3). The depressed group (n=101) revealed significantly higher prevalence of LAN exposure (average intensity, ≥5 lx) compared with that of the nondepressed group (n=415) using a multivariate logistic regression model adjusted for daytime light exposure, insomnia, hypertension, sleep duration, and physical activity [adjusted odds ratio (OR): 1.89; 95% confidence interval (CI), 1.10–3.25; P=0.02]. Consistently, another parameter of LAN exposure (duration of intensity ≥10 lx, ≥30 min) was significantly more prevalent in the depressed than in the nondepressed group (adjusted OR: 1.71; 95% CI, 1.01–2.89; P=0.046). In contrast, UME was not significantly associated with depressive symptoms.

Limitation

Cross-sectional analysis.

Conclusion

These results suggested that LAN exposure in home settings is significantly associated with depressive symptoms in the general elderly population. The risk of depression may be reduced by keeping nighttime bedroom dark.     

Linear and non-linear analysis of the surface electrocardiogram during human ventricular fibrillation shows evidence of order in the underlying mechanism

Ventricular fibrillation (VF) is a poorly understood yet potentially lethal cardiac arrhythmia. The electrocardiogram (ECG) time series of VF is investigated by comparison of the linear and non-linear features of VF time series and surrogates in which internal correlations have been destroyed. From 40 ECG time series of human VF and 40 surrogate time series, three quantities are evaluated: the percentage of the linear time-frequency distribution (TFD) exceeding a threshold, the non-linear coarse-grained correlation dimension (Dcg), and the percentage of diagonal lines in the non-linear recurrence plot longer than 10 elements (D10). It is found that the mean (SD) percent threshold TFD and Dcg are higher for the surrogates (6.7% (1.3) and 5.3 (0.6)) than the VF time series (5.6% (0.7) and 3.8 (0.9)), whereas the mean D10 is higher for the VF time series (49% (13)) than the surrogates (32% (7)). All of these differences are significant (p < 0.0001) and indicate greater order in the VF time series than in the surrogates. It is therefore shown that both linear and non-linear signal analysis demonstrate order in the ECG time series of VF.     

Linear and non-linear analysis of the surface electrocardiogram during human ventricular fibrillation shows evidence of order in the underlying mechanism

Ventricular fibrillation (BF) is a poorly understood yet potentially lethal cardiac arrhythmia. The electrocardiogram (ECG) time series of VF is investigated by comparison of the linear and non-linear features of VF time series and surrogates in which internal correlations have been destroyed. From 40 ECG time series of human VF and 40 surrogate time series, three quantities are evaluated: the percentage of the linear time-frequency distribution (TFD) exceeding a threshold, the non-linear coarsegrained correlation dimension (D_cg), and the percentage of diagonal lines in the non-linear recurrence plot longer than 10 elements (D₁₀). It is found that the mean (SD) percent threshold TFD and D_cg are higher for the surrogates (6.7% (1.3) and 5.3 (0.6)) than the VF time series (5.6% (0.7) and 3.8(0.9)) whereas the mean D₁₀ is higher for the VF time series (49% (13)) than the surrogates (32% (7)). All of these differences are significant (p<0.0001) and indicate greater order in the VF time series than in the surrogates. It is therefore shown that both linear and non-linear signal analysis demonstrate order in the ECG time series of VF.     

Gender differences in cardiac autonomic modulation during medical internship

Medical internship is known to be a time of high stress and long working hours, which increases the risk of depression and cardiovascular disease. Gender differences in medical interns' cardiovascular risk have not been reported previously. Thirty‐eight medical interns (29 males) were repeatedly tested for depressive symptoms using the Hospital Anxiety and Depression Scale and 5‐min spectral analysis of heart rate variability (HRV) at 3‐month intervals during their internship. Among the male interns, the variance of the heart rate decreased at 6, 9, 12 months, and a reduced high frequency, which suggests reduced cardiac parasympathetic modulation, was found at 9 and 12 months into their internship. Increased depressive symptoms were also identified at 12 months in the male group. No significant differences in depression or any of the HRV indices were identified among the female interns during their internship.     

Factors determining the impact of care-giving on caregivers of elderly patients with dementia. A systematic literature review

Introduction

Dementia caregivers suffer a considerable care burden. More than in comparable groups of caregivers or peers, they are confronted with feelings of depression and decreased physical health. Although many studies are set up to determine the link between the stressors in dementia care-giving and the impact on the family caregiver, the results remained inconclusive. Others, depression in caregivers remains the main cause of a premature or acute ending of home care.

Method

The aim of this systematic literature review was to analyse what factors determine the development of depression in caregivers of elderly patients with dementia. Depression was taken as primary outcome as it is shown to be the main reason for caregivers to abandon home care.

Results

Depression occurs in one in three of caregivers and it occurs more frequently in those who care for patients with dementia than in caregivers of patients with other chronic illnesses.

Conclusion

Caregiver characteristics rather than objective care needs of the patients tend to be responsible for the onset of depression. Future research should concentrate on demonstrating links between negative feelings in caregivers and the way the care situation evolves. This can have important implications in home care support.     

Cognitive depressive symptoms associated with delayed heart rate recovery following interpersonal stress in healthy men and women

Among cardiac patients, research suggests that somatic depressive symptoms are more strongly associated with altered cardiovascular responses to stress than cognitive depressive symptoms. This study sought to determine whether this was also the case in healthy individuals. One hundred and ninety-nine adults from the community completed the Beck Depression Inventory II (BDI-II) and underwent psychological laboratory stressors while their blood pressure, heart rate, and heart rate variability were monitored. A cognitive-affective factor and somatic-affective factor were identified within the BDI-II, but only the cognitive factor was associated with reduced heart rate recovery following the stressors in multivariate analyses examining both factors simultaneously. This suggests that cognitive depressive symptoms may be more strongly related to altered stress physiology following psychological stressors.     

Lower resting cardiac autonomic balance in young adults with current major depression

Research on cardiac autonomic function in major depressive disorder (MDD) has predominantly examined cardiac vagal control and adopted a model of reciprocal autonomic balance. A proposed bivariate autonomic continuum uses cardiac autonomic balance (CAB) and cardiac autonomic regulation (CAR) models, derived from normalized values of respiratory sinus arrhythmia and pre‐ejection period, to more adequately index patterns of autonomic control. The purpose of this study was to assess resting levels of CAB and CAR among young adults with and without a current diagnosis of major depression. One hundred forty‐two young adults (n = 65 MDD, n = 77 healthy controls; 20.8 ± 2.6 years) completed a structured diagnostic interview, cardiovascular assessment, and a maximal aerobic fitness test. The findings revealed that CAB, but not CAR, significantly predicted current MDD status (OR = 0.70, 95% CI [0.53, 0.93]), an effect that remained after controlling for aerobic fitness and body mass index. Although CAB was found to be a significant predictor of current MDD status among a sample of young adults, there remained substantial variation in autonomic control that was not captured by the traditional model of reciprocal autonomic balance.     

Colocalisation of neuropeptides, nitric oxide synthase and immunomarkers for catecholamines in nerve fibres of the adult human vas deferens

Single and double-label immunofluorescence methods were used to determine the distribution and patterns of colocalisation of various neuropeptides and nitric oxide synthase (NOS) with the catecholamine synthesising enzymes tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DβH) in nerve fibres within specimens of adult human vas deferens obtained at vasectomy (age range 28 to 83 y). Cholinergic nerve fibres were immunolabelled with an antiserum to vesicular acetylcholine transporter (VAChT). Using the general nerve marker protein gene product 9.5 (PGP) the density of intramural nerve fibres was found to be similar irrespective of age. Many of these axons, especially in the outer 2 muscle layers were TH and DbH-immunoreactive (IR) and were thus confirmed as noradrenergic. Fewer such axons were seen in the inner longitudinal muscle layer. All the noradrenergic nerve fibres also displayed NPY-immunoreactivity with minor populations containing galanin (GAL) or somatostatin (SOM). Nerve fibres lacking TH and DbH-IR were immunoreactive for VAChT and were sparsely distributed throughout the 2 outer muscle layers but more numerous in the inner muscle layer. Nerves lacking TH and DbH were immunoreactive for NPY and some also contained NOS, VIP or CGRP. These results have been compared with those obtained previously from specimens of human neonatal and infant vas deferens where, in contrast to the present results, NOS and VIP were shown to be colocalised with TH in many of the intramuscular nerve fibres. It thus appears that NOS and VIP cease their coexistence with TH in intramuscular nerve fibres of the human vas deferens between the pre- and postpubertal states. In addition to the intramuscular nerve fibres a VAChT-IR subepithelial nerve plexus occurs in the vas deferens and may control the secretory activity of the lining epithelium. Most of these subepithelial nerve fibres were immunoreactive for NPY and many also contained VIP while minor populations were immunoreactive for NOS, GAL, SOM or SP although fibres containing CGRP were not observed. The neuropeptide content of the subepithelial nerve plexus was similar to that observed in the infant, except for an increased density of VIP-IR nerves, which may reflect greater activity of the lining epithelial cells in the adult vas deferens.