Melissa A. Rosenkranz

Alterations in Brain and Immune Function Produced by Mindfulness Meditation

Objective: The underlying changes in biological processes that are associated with reported changes in mental and physical health in response to meditation have not been systematically explored. We performed a randomized, controlled study on the effects on brain and immune function of a well‐known and widely used 8‐week clinical training program in mindfulness meditation applied in a work environment with healthy employees. Methods: We measured brain electrical activity before and immediately after, and then 4 months after an 8‐week training program in mindfulness meditation. Twenty‐five subjects were tested in the meditation group. A wait‐list control group (N = 16) was tested at the same points in time as the meditators. At the end of the 8‐week period, subjects in both groups were vaccinated with influenza vaccine. Results: We report for the first time significant increases in left‐sided anterior activation, a pattern previously associated with positive affect, in the meditators compared with the nonmeditators. We also found significant increases in antibody titers to influenza vaccine among subjects in the meditation compared with those in the wait‐list control group. Finally, the magnitude of increase in left‐sided activation predicted the magnitude of antibody titer rise to the vaccine. Conclusions: These findings demonstrate that a short program in mindfulness meditation produces demonstrable effects on brain and immune function. These findings suggest that meditation may change brain and immune function in positive ways and underscore the need for additional research.

Making a Life Worth Living Neural Correlates of Well-Being

Despite the vast literature that has implicated asymmetric activation of the prefrontal cortex in approach-withdrawal motivation and emotion, no published reports have directly explored the neural correlates of well-being. Eighty-four right-handed adults (ages 57–60) completed self-report measures of eudaimonic well-being, hedonic well-being, and positive affect prior to resting electroencephalography. As hypothesized, greater left than right superior frontal activation was associated with higher levels of both forms of well-being. Hemisphere-specific analyses documented the importance of goal-directed approach tendencies beyond those captured by approach-related positive affect for eudaimonic but not for hedonic well-being. Appropriately engaging sources of appetitive motivation, characteristic of higher left than right baseline levels of prefrontal activation, may encourage the experience of well-being.

Psychological Well-Being and Ill-Being: Do They Have Distinct or Mirrored Biological Correlates?

Background: Increasingly, researchers attend to both positive and negative aspects of mental health. Such distinctions call for clarification of whether psychological well-being and ill-being comprise opposite ends of a bipolar continuum, or are best construed as separate, independent dimensions of mental health. Biology can help resolve this query – bipolarity predicts ‘mirrored’ biological correlates (i.e. well-being and ill-being correlate similarly with biomarkers, but show opposite directional signs), whereas independence predicts ‘distinct’ biological correlates (i.e. well-being and ill-being have different biological signatures). Methods: Multiple aspects of psychological well-being (eudaimonic, hedonic) and ill-being (depression, anxiety, anger) were assessed in a sample of aging women (n = 135, mean age = 74) on whom diverse neuroendocrine (salivary cortisol, epinephrine, norepinephrine, DHEA-S) and cardiovascular factors (weight, waist-hip ratio, systolic and diastolic blood pressure, HDL cholesterol, total/HDL cholesterol, glycosylated hemoglobin) were also measured. Results: Measures of psychological well-being and ill-being were significantly linked with numerous biomarkers, with some associations being more strongly evident for respondents aged 75+. Outcomes for seven biomarkers supported the distinct hypothesis, while findings for only two biomarkers supported the mirrored hypothesis. Conclusion: This research adds to the growing literature on how psychological well-being and mental maladjustment are instantiated in biology. Population-based inquiries and challenge studies constitute important future directions.

Cortisol variation in humans affects memory for emotionally laden and neutral information.

In a test of the effects of cortisol on emotional memory, 90 men were orally administered placebo or 20 or 40 mg cortisol and presented with emotionally arousing and neutral stimuli. On memory tests administered within 1 hr of stimulus presentation, cortisol elevations caused a reduction in the number of errors committed on free-recall tasks. Two evenings later, when cortisol levels were no longer manipulated, inverted-U quadratic trends were found for recognition memory tasks, reflecting memory facilitation in the 20-mg group for both negative and neutral information. Results suggest that the effects of cortisol on memory do not differ substantially for emotional and neutral information. The study provides evidence of beneficial effects of acute cortisol elevations on explicit memory in humans.

Now You Feel It, Now You Don't Frontal Brain Electrical Asymmetry and Individual Differences in Emotion Regulation

Recent theoretical accounts of emotion regulation assign an important role in this process to the prefrontal cortex, yet there is little relevant data available to support this hypothesis. The current study assessed the relation between individual differences in asymmetric prefrontal activation and an objective measure of uninstructed emotion regulation. Forty-seven participants 57 to 60 years old viewed emotionally arousing and neutral visual stimuli while eye-blink startle data were collected. Startle probes were also presented after picture presentation to capture the persistence or attenuation of affect following the offset of an emotional stimulus. Subjects with greater relative left-sided anterior activation in scalp-recorded brain electrical signals displayed attenuated startle magnitude after the offset of negative stimuli. This relation between resting frontal activation and recovery following an aversive event supports the idea of a frontally mediated mechanism involved in one form of automatic emotion regulation.

Affective style and in vivo immune response: neurobehavioral mechanisms.

Considerable evidence exists to support an association between psychological states and immune function. However, the mechanisms by which such states are instantiated in the brain and influence the immune system are poorly understood. The present study investigated relations among physiological measures of affective style, psychological well being, and immune function. Negative and positive affect were elicited by using an autobiographical writing task. Electroencephalography and affect-modulated eye-blink startle were used to measure trait and state negative affect. Participants were vaccinated for influenza, and antibody titers after the vaccine were assayed to provide an in vivo measure of immune function. Higher levels of right-prefrontal electroencephalographic activation and greater magnitude of the startle reflex reliably predicted poorer immune response. These data support the hypothesis that individuals characterized by a more negative affective style mount a weaker immune response and therefore may be at greater risk for illness than those with a more positive affective style.

A comparison of mindfulness-based stress reduction and an active control in modulation of neurogenic inflammation

Psychological stress is a major provocative factor of symptoms in chronic inflammatory conditions. In recent years, interest in addressing stress responsivity through meditation training in health-related domains has increased astoundingly, despite a paucity of evidence that reported benefits are specific to meditation practice. We designed the present study to rigorously compare an 8-week Mindfulness-Based Stress Reduction (MBSR) intervention to a well-matched active control intervention, the Health Enhancement Program (HEP) in ability to reduce psychological stress and experimentally-induced inflammation. The Trier Social Stress Test (TSST) was used to induce psychological stress and inflammation was produced using topical application of capsaicin cream to forearm skin. Immune and endocrine measures of inflammation and stress were collected both before and after MBSR training. Results show those randomized to MBSR and HEP training had comparable post-training stress-evoked cortisol responses, as well as equivalent reductions in self-reported psychological distress and physical symptoms. However, MBSR training resulted in a significantly smaller post-stress inflammatory response compared to HEP, despite equivalent levels of stress hormones. These results suggest behavioral interventions designed to reduce emotional reactivity may be of therapeutic benefit in chronic inflammatory conditions. Moreover, mindfulness practice, in particular, may be more efficacious in symptom relief than the well-being promoting activities cultivated in the HEP program.

Rapid changes in histone deacetylases and inflammatory gene expression in expert meditators

BACKGROUND A growing body of research shows that mindfulness meditation can alter neural, behavioral and biochemical processes. However, the mechanisms responsible for such clinically relevant effects remain elusive. METHODS Here we explored the impact of a day of intensive practice of mindfulness meditation in experienced subjects (n=19) on the expression of circadian, chromatin modulatory and inflammatory genes in peripheral blood mononuclear cells (PBMC). In parallel, we analyzed a control group of subjects with no meditation experience who engaged in leisure activities in the same environment (n=21). PBMC from all participants were obtained before (t1) and after (t2) the intervention (t2-t1=8h) and gene expression was analyzed using custom pathway focused quantitative-real time PCR assays. Both groups were also presented with the Trier Social Stress Test (TSST). RESULTS Core clock gene expression at baseline (t1) was similar between groups and their rhythmicity was not influenced in meditators by the intensive day of practice. Similarly, we found that all the epigenetic regulatory enzymes and inflammatory genes analyzed exhibited similar basal expression levels in the two groups. In contrast, after the brief intervention we detected reduced expression of histone deacetylase genes (HDAC 2, 3 and 9), alterations in global modification of histones (H4ac; H3K4me3) and decreased expression of pro-inflammatory genes (RIPK2 and COX2) in meditators compared with controls. We found that the expression of RIPK2 and HDAC2 genes was associated with a faster cortisol recovery to the TSST in both groups. CONCLUSIONS The regulation of HDACs and inflammatory pathways may represent some of the mechanisms underlying the therapeutic potential of mindfulness-based interventions. Our findings set the foundation for future studies to further assess meditation strategies for the treatment of chronic inflammatory conditions.

Socioeconomic status predicts objective and subjective sleep quality in aging women.

Objective: To test the hypothesis that socioeconomic status (SES) would be associated with sleep quality measured objectively, even after controlling for related covariates (health status, psychosocial characteristics). Epidemiological studies linking SES and sleep quality have traditionally relied on self-reported assessments of sleep. Methods: Ninety-four women, 61 to 90 years of age, participated in this study. SES was determined by pretax household income and years of education. Objective and subjective assessments of sleep quality were obtained using the NightCap sleep system and the Pittsburgh Sleep Quality Index (PSQI), respectively. Health status was determined by subjective health ratings and objective measures of recent and chronic illnesses. Depressive symptoms and neuroticism were quantified using the Center for Epidemiological Studies Depression Scale and the Neuroticism subscale of the NEO Personality Inventory, respectively. Results: Household income significantly predicted sleep latency and sleep efficiency even after adjusting for demographic factors, health status, and psychosocial characteristics. Income also predicted PSQI scores, although this association was significantly attenuated by inclusion of neuroticism in multivariate analyses. Education predicted both sleep latency and sleep efficiency, but the latter association was partially reduced after health status and psychosocial measures were included in analyses. Education predicted PSQI sleep efficiency component scores, but not global scores. Conclusions: These results suggest that SES is robustly linked to both subjective and objective sleep quality, and that health status and psychosocial characteristics partially explain these associations. SES = socioeconomic status; PSQI = Pittsburgh Sleep Quality Index; GCRC = General Clinical Research Center; CES-D = Center for Epidemiological Studies Depression Scale.

Substance P at the nexus of mind and body in chronic inflammation and affective disorders

For decades, research has demonstrated that chronic diseases characterized by dysregulation of inflammation are particularly susceptible to exacerbation by stress and emotion. Likewise, rates of depression and anxiety are overrepresented in individuals suffering from chronic inflammatory disease. In recent years, substance P has been implicated in both the pathophysiology of inflammatory disease and the pathophysiology of depression and anxiety by 2 parallel fields of study. This review integrates the literature from these 2 parallel fields and examines the possibility that substance P dysregulation may be a point of convergence underlying the overlap of chronic inflammatory disease and mood and anxiety disorders. First, the involvement of substance P in peripheral inflammation and in the immune events associated with chronic inflammatory disease is discussed, with a focus on inflammatory bowel disease and asthma. Next, the function of substance P in the communication of peripheral inflammation to the brain is considered. Finally, to complete the bidirectional loop of brain-immune interactions, substance P expression in anxiety and depression as well as its potential role in the neural regulation of peripheral inflammation is reviewed.