Richard P. Sloan

An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus

With continued debate over the functional significance of adult neurogenesis, identifying an in vivo correlate of neurogenesis has become an important goal. Here we rely on the coupling between neurogenesis and angiogenesis and test whether MRI measurements of cerebral blood volume (CBV) provide an imaging correlate of neurogenesis. First, we used an MRI approach to generate CBV maps over time in the hippocampal formation of exercising mice. Among all hippocampal subregions, exercise was found to have a primary effect on dentate gyrus CBV, the only subregion that supports adult neurogenesis. Moreover, exercise-induced increases in dentate gyrus CBV were found to correlate with postmortem measurements of neurogenesis. Second, using similar MRI technologies, we generated CBV maps over time in the hippocampal formation of exercising humans. As in mice, exercise was found to have a primary effect on dentate gyrus CBV, and the CBV changes were found to selectively correlate with cardiopulmonary and cognitive function. Taken together, these findings show that dentate gyrus CBV provides an imaging correlate of exercise-induced neurogenesis and that exercise differentially targets the dentate gyrus, a hippocampal subregion important for memory and implicated in cognitive aging.

Relation between depression after coronary artery bypass surgery and 12-month outcome: a prospective study

BACKGROUND The association of depression with cardiac events has been investigated mainly in community cohorts, in patients undergoing catheterisation, or in patients who have had myocardial infarction. We have assessed the effect of depression on outcomes after coronary artery bypass graft (CABG) surgery. METHODS In a prospective study, we followed up for 1 year 207 men and 102 women, who had undergone coronary artery bypass graft surgery. We assessed depression with a structured psychiatric interview (diagnostic interview schedule) and a questionnaire (Beck depression inventory) before discharge. Cardiac events included angina or heart failure that needed admission to hospital, myocardial infarction, cardiac arrest, percutaneous transluminal coronary angioplasty, repeat CABG, and cardiac mortality. Non-cardiac events consisted of all other reasons for mortality or readmission. FINDINGS 63 patients (20%) met modified diagnostic statistical manual IV criteria for major depressive disorder. At 12 months, 17 (27%) of these patients had a cardiac event compared with 25 of 246 (10%) who were not depressed (p<0.0008). Five variables had significant univariate associations with cardiac events: sex, living alone, low ejection fraction (<0.35), length of hospital stay, and depression. In a Cox proportional-hazard model with these five and two other variables of cardiac severity, major depressive disorder (risk ratio 2.3 [95% CI 1.17-4.56]), low ejection fraction (2.3 [1.07-5.03]), and female sex (2.4 [1.24-4.44]) were associated with adverse outcomes. Depression did not predict deaths or admissions for non-cardiac events. INTERPRETATION Depression is an important independent risk factor for cardiac events after CABG surgery.

Mixed-effects models in psychophysiology

The current methodological policy in Psychophysiology stipulates that repeated-measures designs be analyzed using either multivariate analysis of variance (ANOVA) or repeated-measures ANOVA with the Greenhouse-Geisser or Huynh-Feldt correction. Both techniques lead to appropriate type I error probabilities under general assumptions about the variance-covariance matrix of the data. This report introduces mixed-effects models as an alternative procedure for the analysis of repeated-measures data in Psychophysiology. Mixed-effects models have many advantages over the traditional methods: They handle missing data more effectively and are more efficient, parsimonious, and flexible. We described mixed-effects modeling and illustrated its applicability with a simple example.

Maternal stress responses and anxiety during pregnancy: effects on fetal heart rate.

This study examined the effect of an acute maternal stress response and anxiety on fetal heart rate. Seventeen healthy, 3rd-trimester pregnant women (mean age = 26 +/- 6 years) were instrumented for continuous electrocardiography, blood pressure (BP), respiration, and fetal heart rate (HR). Subjects completed the state anxiety subscale of the State Trait Personality Inventory (STPI), then rested quietly in a semirecumbent position for a 5-min baseline period, followed by either a 5-min arithmetic or Stroop color-word task. Over the entire 5-min stress period and when averaged across all subjects, the stressors led to significant increases in maternal systolic BP and respiratory rate but changes in maternal HR, diastolic BP, and fetal HR were not significant. However, when subjects were dichotomized into groups that had above or below average anxiety scores [ANX(+) and ANX(-)], both groups had similar respiration rate increases to the stressors, but the BP and fetal heart rate (FHR) responses were significantly different. Women in the ANX(-) group had significantly greater BP responses compared to women in the ANX(+) group whereas the fetuses of ANX(+) women showed significant HR increases and the fetuses of ANX(-) women exhibited nonsignificant decreases. These findings suggest that womens acute emotional reactivity during pregnancy can influence fetal HR patterns and that a stress-induced increase in maternal BP is not the primary signal by which a womens stress response is transduced to her fetus. The results are consistent with the hypothesis that maternal psychological variables may shape the neurobehavioral development of the fetus.

Multiple Metabolic Syndrome Is Associated With Lower Heart Rate Variability: The Atherosclerosis Risk in Communities Study

OBJECTIVE To test at the population level whether people with multiple metabolic syndrome (MMS) disorders have reduced cardiac autonomic activity (CAA). RESEARCH DESIGN AND METHODS We examined the association between the level of CAA and MMS disorders, at the degree of clustering and the segregate combination levels, using a random sample of 2,359 men and women aged 45–64 years from the biracial, population-based Atherosclerosis Risk in Communities (AR1C) Study. Supine resting 2-min beat-to-beat heart rate data were collected. High-frequency (HF) (0.15–0.35 Hz) and low-frequency (LF) (0.025–0.15 Hz) spectral powers, the ratio of LF to HF, and the SD of all normal R-R intervals (SDNN) were used as the conventional indices of heart rate variability (HRV) to measure CAA. The MMS disorders included hypertension, type 2 diabetes, and dyslipidemia. RESULTS HRV indices were significantly lower in individuals with MMS disorders. The multivariable adjusted mean HF was 0.85 (beat/min)2 in subjects with all three MMS disorders, in contrast to 1.31 beat/min)2 in subjects without any MMS disorder. At the segregated combination level, the multivariable adjusted means ± SEM of HF were 1.34 ± 0.05, 1.16 ± 0.05, 1.01 ± 0.17, and 1.34 ± 0.05 (beat/min)2, respectively, for subjects without any MMS disorder, with hypertension only, with diabetes only, and with dyslipidemia only, and the means ± SEM of HF were 0.93 ± 0.04,0.70 ± 0.15, and 1.20 ± 0.05 eat/min)2, respectively, for subjects with diabetes and hypertension, diabetes and dyslipidemia, and hypertension and dyslipidemia. An increase in fasting insulin of 1 SD was associated with 88% higher odds of having a lower HF The pattern of associations was similar for LF and SDNN. CONCLUSIONS These findings suggest that MMS disorders adversely affect cardiac autonomic control and a reduced cardiac autonomic control may contribute to the increased risk of subsequent cardiovascular events in individuals who exhibit MMS disorders.

Molecular drivers and cortical spread of lateral entorhinal cortex dysfunction in preclinical Alzheimer’s disease

The entorhinal cortex has been implicated in the early stages of Alzheimers disease, which is characterized by changes in the tau protein and in the cleaved fragments of the amyloid precursor protein (APP). We used a high-resolution functional magnetic resonance imaging (fMRI) variant that can map metabolic defects in patients and mouse models to address basic questions about entorhinal cortex pathophysiology. The entorhinal cortex is divided into functionally distinct regions, the medial entorhinal cortex (MEC) and the lateral entorhinal cortex (LEC), and we exploited the high-resolution capabilities of the fMRI variant to ask whether either of them was affected in patients with preclinical Alzheimers disease. Next, we imaged three mouse models of disease to clarify how tau and APP relate to entorhinal cortex dysfunction and to determine whether the entorhinal cortex can act as a source of dysfunction observed in other cortical areas. We found that the LEC was affected in preclinical disease, that LEC dysfunction could spread to the parietal cortex during preclinical disease and that APP expression potentiated tau toxicity in driving LEC dysfunction, thereby helping to explain regional vulnerability in the disease.

Claims about religious involvement and health outcomes.

Claims about religion, spirituality, and health have recently appeared with increasing frequency, in both the popular media and professional journals. These claims have asserted that there are a great many studies in the literature that have examined relations between religious involvement and health outcomes and that the majority of them have shown that religious people are healthier. We examined the validity of these claims in two ways: (a) To determine the percentage of articles in the literature that were potentially relevant to such a claim, we identified all English-language articles with published abstracts identified by a Medline search using the search term religion in the year 2000, and (b) to examine the quality of the data in articles cited as providing support for such a claim, we examined all articles in the area of cardiovascular disease and hypertension cited by two comprehensive reviews of the literature.Of the 266 articles published in the year 2000 and identified by the Medline search, only 17% were relevant to claims of health benefits associated with religious involvement. About half of the articles cited in the comprehensive reviews were irrelevant to these claims. Of those that actually were relevant, many either had significant methodological flaws or were misrepresented, leaving only a few articles that could truly be described as demonstrating beneficial effects of religious involvement. We conclude that there is little empirical basis for assertions that religious involvement or activity is associated with beneficial health outcomes.

Cardiac autonomic control and hostility in healthy subjects

Abstract Disordered autonomic regulation of the cardiovascular system has been implicated in sudden cardiac death and coronary artery disease in numerous studies. Bigger et al 1 showed that survival after myocardial infarction was predicted by high-frequency (HF) power of the heart period power spectrum, a measure of vagal modulation of RR intervals, 2 by power in other frequency bands, and by the low-frequency (LF) to HF power ratio, a measure that has been used to estimate sympathovagal balance. Increased heart rate, reflecting global cardiac autonomic control, is associated with development of atherosclerosis in animal models 3 and age-adjusted levels of atherogenic lipoproteins in humans. 4 Heart rate-lowering interventions such as surgical ablation of the sinoatrial node and β-adrenergic antagonists have antiatherogenic effects. 3 Cardiovascular regulation by the autonomic nervous system may link negative personality characteristics, e.g., hostility, with increased risk of coronary artery disease, an association generally supported by available data. 5,6 Two views about the nature of the link, the constitutional and the transactional theories, specify different mechanisms. The constitutional theory holds that the autonomie activity associated with risk of coronary artery disease is caused by a constitutional characteristic which also accounts for hostility. 5 In this view, hostility is a marker of factors that influence brainstem cardioregulatory centers. The transactional theory holds that hostile persons interact with their environment in a way that creates interpersonal conflict and reduces social support. 5 Since in laboratory experiments, psychological Stressors decrease HF power in the heart period power spectrum, 7 the stressfulness of the transactions that persons high in hostility have with their interpersonal environments suggests an inverse relation between hostility and HF power, which in turn may increase risk of coronary artery disease.

Effect of mental stress throughout the day on cardiac autonomic control

Although many laboratory studies have demonstrated changes in cardiac autonomic control during psychological stress, few have attempted to demonstrate this effect in ambulatory subjects. To address this issue, 24-h electrocardiographic recordings of 33 healthy subjects were analyzed for RR interval and heart period variability (HPV) responses associated with periodic diary entries measuring physical position, negative effect, and time of day. A total of 362 diary entries were made during the 24-h sessions, each in response to a device which signaled on an average of once per hour. HPV was analyzed in the frequency domain, yielding estimates of spectral power in low (LF) and high (HF) frequency bands, as well as the LF/HF ratio. Because of the high correlations of the measures of negative affect (alpha = 0.91), they were combined to create a single index of stress. Multivariate analysis was used to assess the effect of individual subject differences, physical position, and stress on RR interval and HPV. Results revealed significant effects of individual differences, stress, and physical position on RR interval, with increases in stress associated with decreases in RR interval as expected. HF power was significantly lower and the LF/HF ratio significantly higher in the standing compared with the sitting position. Psychological stress was significantly associated with an increase in the LF/HF ratio, suggesting increases in the relative predominance of sympathetic nervous system activity during stressful periods of the day. Overall, these findings suggest that in ambulatory normal subjects, cardiac autonomic control varies throughout the day as a function of self-reported stress.

Vagal rebound and recovery from psychological stress.

Objective To characterize cardiovascular recovery and examine the possible relationship of vagal activity and reflexes to risk for heart disease. Methods Subjects performed cold pressor and mental arithmetic tasks. Heart rate, heart period variability, and pre-ejection period were obtained for 1 minute before, during, and after each task (Experiment 1). In the second experiment, subjects performed a Stroop color-word task and a mental arithmetic task. Heart rate, heart period variability, blood pressure, and baroreflex sensitivity were obtained during the 5-minute baseline, task, and recovery periods (Experiment 2). Results In Experiment 1, heart rate during recovery was lower than baseline despite continued pre-ejection period shortening, whereas recovery heart period variability was higher than baseline. In Experiment 2, blood pressure increased throughout the session. However, recovery heart rate after mental arithmetic was lower than baseline heart rate, and heart period variability was higher during both recovery periods than during baseline. Vagal rebound, a sharp increase in variability in the first minute of recovery, was reduced in men in Experiment 1 and in individuals with a family history of cardiovascular disease in Experiment 2 and was associated with degree of change in baroreflex sensitivity between task and rest. Conclusions Cardiovascular recovery from stress is associated with increased vagal modulation despite residual sympathetic activation. Vagal rebound may be involved in mechanisms resetting the baroreflex sensitivity at the onset and offset of stress. Diminished vagal rebound during recovery from stress is associated with standard risk factors for cardiovascular disease. The results support an association between attenuated vagal reflexes and risk for cardiovascular disease.