Gregory L. Fricchione

Functional brain mapping of the relaxation response and meditation.

&NA; Meditation is a conscious mental process that induces a set of integrated physiologic changes termed the relaxation response. Functional magnetic resonance imaging (fMRI) was used to identify and characterize the brain regions that are active during a simple form of meditation. Significant (p <10−7) signal increases were observed in the group‐averaged data in the dorsolateral prefrontal and parietal cortices, hippocampus/parahippocampus, temporal lobe, pregenual anterior cingulate cortex, striatum, and pre‐ and post‐central gyri during meditation. Global fMRI signal decreases were also noted, although these were probably secondary to cardiorespiratory changes that often accompany meditation. The results indicate that the practice of meditation activates neural structures involved in attention and control of the autonomic nervous system.

Chronic variable stress activates hematopoietic stem cells

Exposure to psychosocial stress is a risk factor for many diseases, including atherosclerosis. Although incompletely understood, interaction between the psyche and the immune system provides one potential mechanism linking stress and disease inception and progression. Known cross-talk between the brain and immune system includes the hypothalamic-pituitary-adrenal axis, which centrally drives glucocorticoid production in the adrenal cortex, and the sympathetic-adrenal-medullary axis, which controls stress-induced catecholamine release in support of the fight-or-flight reflex. It remains unknown, however, whether chronic stress changes hematopoietic stem cell activity. Here we show that stress increases proliferation of these most primitive hematopoietic progenitors, giving rise to higher levels of disease-promoting inflammatory leukocytes. We found that chronic stress induced monocytosis and neutrophilia in humans. While investigating the source of leukocytosis in mice, we discovered that stress activates upstream hematopoietic stem cells. Under conditions of chronic variable stress in mice, sympathetic nerve fibers released surplus noradrenaline, which signaled bone marrow niche cells to decrease CXCL12 levels through the β3-adrenergic receptor. Consequently, hematopoietic stem cell proliferation was elevated, leading to an increased output of neutrophils and inflammatory monocytes. When atherosclerosis-prone Apoe−/− mice were subjected to chronic stress, accelerated hematopoiesis promoted plaque features associated with vulnerable lesions that cause myocardial infarction and stroke in humans.

Cell-Surface Estrogen Receptors Mediate Calcium-Dependent Nitric Oxide Release in Human Endothelia

BACKGROUND Although estrogen replacement therapy has been associated with reduction of cardiovascular events in postmenopausal women, the mechanism for this benefit remains unclear. Because nitric oxide (NO) is considered an important endothelium-derived relaxing factor and may function to protect blood vessels against atherosclerotic development, we investigated the acute effects of physiological levels of estrogen on NO release from human internal thoracic artery endothelia and human arterial endothelia in culture. METHODS AND RESULTS We tested the hypothesis that estrogen acutely stimulates constitutive NO synthase activity in human endothelial cells by acting on a cell-surface receptor. NO release was measured in real time with an amperometric probe. 17beta-Estradiol exposure to internal thoracic artery endothelia and human arterial endothelia in culture stimulated NO release within seconds in a concentration-dependent manner. 17beta-Estradiol conjugated to bovine serum albumin also stimulated NO release, suggesting action through a cell-surface receptor. Tamoxifen, an estrogen receptor inhibitor, antagonized this action. We further showed with the use of dual emission microfluorometry that 17beta-estradiol-stimulated release of endothelial NO was dependent on the initial stimulation of intracellular calcium transients. CONCLUSIONS Physiological doses of estrogen immediately stimulate NO release from human endothelial cells through activation of a cell-surface estrogen receptor that is coupled to increases in intracellular calcium.

Standardised mindfulness-based interventions in healthcare : An overview of systematic reviews and meta-analyses of RCTs

Background Mindfulness-based therapies are being used in a wide range of common chronic conditions in both treatment and prevention despite lack of consensus about their effectiveness in different patient categories. Objective To systematically review the evidence of effectiveness MBSR and MBCT in different patient categories. Methods A systematic review and meta-analysis of systematic reviews of RCTs, using the standardized MBSR or MBCT programs. We used PRISMA guidelines to assess the quality of the included reviews and performed a random effects meta-analysis with main outcome measure Cohen’s d. All types of participants were considered. Results The search produced 187 reviews: 23 were included, covering 115 unique RCTs and 8,683 unique individuals with various conditions. Compared to wait list control and compared to treatment as usual, MBSR and MBCT significantly improved depressive symptoms (d=0.37; 95%CI 0.28 to 0.45, based on 5 reviews, N=2814), anxiety (d=0.49; 95%CI 0.37 to 0.61, based on 4 reviews, N=2525), stress (d=0.51; 95%CI 0.36 to 0.67, based on 2 reviews, N=1570), quality of life (d=0.39; 95%CI 0.08 to 0.70, based on 2 reviews, N=511) and physical functioning (d=0.27; 95%CI 0.12 to 0.42, based on 3 reviews, N=1015). Limitations include heterogeneity within patient categories, risk of publication bias and limited long-term follow-up in several studies. Conclusion The evidence supports the use of MBSR and MBCT to alleviate symptoms, both mental and physical, in the adjunct treatment of cancer, cardiovascular disease, chronic pain, depression, anxiety disorders and in prevention in healthy adults and children.

Relation between myocardial infarction, depression, hostility, and death.

OBJECTIVE To examine the independent impact of major depression and hostility on mortality rate at 6 months and 12 months after discharge from the hospital in patients with a myocardial infarction. METHOD Three hundred thirty-one patients were prospectively evaluated for depression with a modified version of the National Institute of Mental Health Diagnostic Interview Schedule for major depressive episode. The Cook Medley Hostility Scale data were analyzed by chi(2) procedures for nominal and categoric data, and Student t test was used for continuous data types. RESULTS Depression was a significant predictor of death at 12 months (P =. 04) but not at 6 months (P =.08). Hostility was not found to be a predictor of death at 6 months or 12 months. CONCLUSIONS Major depression in patients hospitalized after myocardial infarction is a significant univariable predictor of death at 12 months, although it was not a statistically significant predictor after adjusting for other variables. Hostility is not a predictor of death. Prospective studies are needed to determine the impact of aggressive treatment of depression on post-myocardial infarction survival.

The placebo effect and relaxation response : neural processes and their coupling to constitutive nitric oxide

The placebo effect appears to be a real phenomenon as is the scientifically demonstrated and examined relaxation response. Given this, we attempt to understand how these phenomena work in light of our current understanding of central and peripheral nervous system mechanisms. Central to our hypothesis is the significance of norepinephrine, nitric oxide and opioid signaling both in the central and peripheral nervous system. In this regard, we find that nitric oxide controls norepinephrine processes on many levels, including synthesis, release and actions. In closing, we conclude that enough scientific information exists to support these phenomena as actual physical processes that can be harnessed to provide better patient care.

Anxiety and Anger in Patients with Ventricular Tachyarrhythmias. Responses after Automatic Internal Cardioverter Defibrillator Implantation

In order to assess the psychological profile of patients with malignant ventricular tachyarrhythmias, eight patients who underwent implantation of the automatic internal cardioverter defibrillator for refractory arrhythmias were evaluated. Six men and two women with a mean age of 53 years were examined with the Symptom Checklist‐90, the State Trait Personality Inventory and a specifically designed questionnaire about the automatic internal cardioverter defibrillator. The group studied manifested high degrees of both anger and anxiety compared to normal controls or to other medically ill populations. The trait scores remained essentially unchanged before and after the AICD implantation. The state of anxiety was markedly reduced by 26 percentage points after implantation (P < 0.01), while the state of anger remained unchanged. In evaluating the number of AICD discharges, it was observed that the number of discharges in the first 6 months was higher than that observed in the subsequent follow‐up period (mean 30 months). The reduction in AICD discharges demonstrated a trend (P = 0.094). Patient acceptance of the automatic internal cardioverter defibrillator was high. They became accustomed to the pulse generator after a mean of 3.6 months. The defibrillator permitted resumption of normal activities. If the device became battery depleted, all patients would insist on replacement. The evaluation of this group of patients with malignant ventricular arrhythmias indicates a high degree of anxiety and anger, which potentially may influence outcome. The reduction in defibrillator discharges after the first 6 months in addition to a reduced state of anxiety is a relationship that merits further investigation. (PACE, Vol. 12 February 1989)

Relaxation Response Induces Temporal Transcriptome Changes in Energy Metabolism, Insulin Secretion and Inflammatory Pathways

The relaxation response (RR) is the counterpart of the stress response. Millennia-old practices evoking the RR include meditation, yoga and repetitive prayer. Although RR elicitation is an effective therapeutic intervention that counteracts the adverse clinical effects of stress in disorders including hypertension, anxiety, insomnia and aging, the underlying molecular mechanisms that explain these clinical benefits remain undetermined. To assess rapid time-dependent (temporal) genomic changes during one session of RR practice among healthy practitioners with years of RR practice and also in novices before and after 8 weeks of RR training, we measured the transcriptome in peripheral blood prior to, immediately after, and 15 minutes after listening to an RR-eliciting or a health education CD. Both short-term and long-term practitioners evoked significant temporal gene expression changes with greater significance in the latter as compared to novices. RR practice enhanced expression of genes associated with energy metabolism, mitochondrial function, insulin secretion and telomere maintenance, and reduced expression of genes linked to inflammatory response and stress-related pathways. Interactive network analyses of RR-affected pathways identified mitochondrial ATP synthase and insulin (INS) as top upregulated critical molecules (focus hubs) and NF-κB pathway genes as top downregulated focus hubs. Our results for the first time indicate that RR elicitation, particularly after long-term practice, may evoke its downstream health benefits by improving mitochondrial energy production and utilization and thus promoting mitochondrial resiliency through upregulation of ATPase and insulin function. Mitochondrial resiliency might also be promoted by RR-induced downregulation of NF-κB-associated upstream and downstream targets that mitigates stress.

Enkelytin and opioid peptide association in invertebrates and vertebrates: immune activation and pain

Abstract Invertebrates contain an opioid precursor, proenkephalin. Enkelytin, an antibacterial peptide, is found in invertebrate proenkephalin, exhibiting 98% sequence identity with mammalian enkephalin. Here, George Stefano and colleagues surmise that the function of enkelytin is to attack bacteria and allow time for the immunocyte-stimulating capabilities of the opioid peptides to emerge. Furthermore, they propose that pain itself is a component of this response.

Intravenous lorazepam in neuroleptic-induced catatonia

Presented here are four cases of catatonic reactions which were felt to be neuroleptic induced. Intravenous lorazepam was rapidly effective in reversing the catatonia and attendant symptoms. Lorazepams previous uses and pharmacological profile are discussed. Reviewed briefly are catatonia and its neuroleptic-induced forms. Possible mechanisms responsible for the therapeutic effect of intravenous lorazepam in these cases are then examined.