A randomized, controlled trial of mindfulness-based stress reduction in HIV infection.

OBJECTIVE: Evidence links depression and stress to more rapid progression of HIV-1 disease. We conducted a randomized controlled trial to test whether an intervention aimed at improving stress management and emotion regulation, mindfulness-based stress reduction (MBSR), would improve immunological (i.e. CD4+ T-cell counts) and psychological outcomes in persons with HIV-1 infection. METHODS: We randomly assigned participants with HIV-1 infection and CD4 T-cell counts >350 cells/µl who were not on antiretroviral therapy in a 1:1 ratio to either an MBSR group (n = 89) or an HIV disease self-management skills group (n = 88). The study was conducted at the University of California at San Francisco. We assessed immunologic (CD4, c-reactive protein, IL-6, and d-dimer) and psychological measures (Beck Depression Inventory for depression, modified Differential Emotions Scale for positive and negative affect, Perceived stress-scale, and mindfulness) at 3, 6 and 12 months after initiation of the intervention; we used multiple imputation to address missing values. RESULTS: We observed statistically significant improvements from baseline to 3-months within the MBSR group in depression, positive and negative affect, perceived stress, and mindfulness; between group differences in change were significantly greater in the MBSR group only for positive affect (per item difference on DES-positive 0.25, 95% CI 0.049, 0.44, p = .015). By 12 months the between group difference in positive affect was not statistically significant, although both groups had trends toward improvements compared to baseline in several psychological outcomes that were maintained at 12-months; these improvements were only statistically significant for depression and negative affect in the MBSR group and perceived stress for the control group. The groups did not differ significantly on rates of antiretroviral therapy initiation (MBSR = 39%, control = 29%, p = .22). After 12 months, the mean decrease in CD4+ T-cell count was 49.6 cells/µl in participants in the MBSR arm, compared to 54.2 cells/µl in the control group, a difference of 4.6 cells favoring the MBSR group (95% CI, -44.6, 53.7, p = .85). The between group differences in other immunologic-related outcomes (c-reactive protein, IL-6, HIV-1 viral load, and d-dimer) were not statistically significant at any time point. CONCLUSIONS: MBSR improved positive affect more than an active control arm in the 3 months following the start of the intervention. However, this difference was not maintained over the 12-month follow-up and there were no significant differences in immunologic outcomes between intervention groups. These results emphasize the need for further carefully designed research if we are to translate evidence linking psychological states to immunological outcomes into evidence-based clinical practices.

Effects of a mindfulness-based weight loss intervention in adults with obesity: A randomized clinical trial.

OBJECTIVE: To determine whether adding mindfulness-based eating and stress management practices to a diet-exercise program improves weight loss and metabolic syndrome components. METHODS: In this study 194 adults with obesity were randomized to a 5.5-month program with or without mindfulness training and identical diet-exercise guidelines. Intention-to-treat analyses with multiple imputation were used for missing data. The primary outcome was 18-month weight change. RESULTS: Estimated effects comparing the mindfulness to control arm favored the mindfulness arm in (a) weight loss at 12 months, -1.9 kg (95% CI: -4.5, 0.8; P = 0.17), and 18 months, -1.7 kg (95% CI: -4.7, 1.2; P = 0.24), though not statistically significant; (b) changes in fasting glucose at 12 months, -3.1 mg/dl (95% CI: -6.3, 0.1; P = 0.06), and 18 months, -4.1 mg/dl (95% CI: -7.3, -0.9; P = 0.01); and (c) changes in triglyceride/HDL ratio at 12 months, -0.57 (95% CI: -0.95, -0.18; P = 0.004), and 18 months, -0.36 (95% CI: -0.74, 0.03; P = 0.07). Estimates for other metabolic risk factors were not statistically significant, including waist circumference, blood pressure, and C-reactive protein. CONCLUSIONS: Mindfulness enhancements to a diet-exercise program did not show substantial weight loss benefit but may promote long-term improvement in some aspects of metabolic health in obesity that requires further study.

Anticipatory sensitization to repeated stressors: the role of initial cortisol reactivity and meditation/emotion skills training.

Anticipation may play a role in shaping biological reactions to repeated stressors-a common feature of modern life. We aimed to demonstrate that: (a) individuals who display a larger cortisol response to an initial stressor exhibit progressive anticipatory sensitization, showing progressively higher cortisol levels before subsequent exposures, and (b) attention/emotional skills training can reduce the magnitude of this effect on progressive anticipatory sensitization. Female school teachers (N=76) were randomly assigned to attention/emotion skills and meditation training or to a control group. Participants completed 3 separate Trier Social Stress Tests (TSST): at baseline (Session 1), post-training (Session 2), and five months post (Session 3). Each TSST session included preparing and delivering a speech and performing an arithmetic task in front of critical evaluators. In each session participants' salivary cortisol levels were determined before and after the stressor. Control participants with larger cortisol reactivity to the first stressor showed increasing anticipatory (pre-stressor) cortisol levels with each successive stressor exposure (TSST session)-suggesting progressive anticipatory sensitization. Yet this association was absent in the training group. Supplementary analyses indicated that these findings occurred in the absence of group differences in cortisol reactivity. Findings suggest that the stress response can undergo progressive anticipatory sensitization, which may be modulated by attention/emotion-related processes. An important implication of the construct of progressive anticipatory sensitization is a possible self-perpetuating effect of stress reactions, providing a candidate mechanism for the translation of short-to-long-term stress reactions.

Follow your breath: respiratory interoceptive accuracy in experienced meditators.

Attention to internal bodily sensations is a core feature of mindfulness meditation. Previous studies have not detected differences in interoceptive accuracy between meditators and nonmeditators on heartbeat detection and perception tasks. We compared differences in respiratory interoceptive accuracy between meditators and nonmeditators in the ability to detect and discriminate respiratory resistive loads and sustain accurate perception of respiratory tidal volume during nondistracted and distracted conditions. Groups did not differ in overall performance on the detection and discrimination tasks; however, meditators were more accurate in discriminating the resistive load with the lowest ceiling effect. Meditators were also more accurate during the nondistracted tracking task at a lag time of 1 s following the breath. Results provide initial support for the notion that meditators have greater respiratory interoceptive accuracy compared to nonmeditators.

Self-reported mindfulness and cortisol during a Shamatha meditation retreat.

OBJECTIVE: Cognitive perseverations that include worry and rumination over past or future events may prolong cortisol release, which in turn may contribute to predisease pathways and adversely affect physical health. Meditation training may increase self-reported mindfulness, which has been linked to reductions in cognitive perseverations. However, there are no reports that directly link self-reported mindfulness and resting cortisol output. Here, the authors investigate this link. METHODS: In an observational study, we measured self-reported mindfulness and p.m. cortisol near the beginning and end of a 3-month meditation retreat (N = 57). RESULTS: Mindfulness increased from pre- to post-retreat, F(1, 56) = 36.20, p < .001. Cortisol did not significantly change. However, mindfulness was inversely related to p.m. cortisol at pre-retreat, r(53) = -.31, p < .05, and post-retreat, r(53) = -.30, p < .05, controlling for age and body mass index. Pre to postchange in mindfulness was associated with pre to postchange in p.m. cortisol, ß = -.37, t(49) = 2.30, p < .05: Larger increases in mindfulness were associated with decreases in p.m. cortisol, whereas smaller increases (or slight decreases) in mindfulness were associated with an increase in p.m. cortisol. CONCLUSIONS: These data suggest a relation between self-reported mindfulness and resting output of the hypothalamic-pituitary-adrenal system. Future work should aim to replicate this finding in a larger cohort and determine stronger inference about causality by using experimental designs that include control-group conditions.

Contemplative/emotion training reduces negative emotional behavior and promotes prosocial responses.

Contemplative practices are believed to alleviate psychological problems, cultivate prosocial behavior and promote self-awareness. In addition, psychological science has developed tools and models for understanding the mind and promoting well-being. Additional effort is needed to combine frameworks and techniques from these traditions to improve emotional experience and socioemotional behavior. An 8-week intensive (42 hr) meditation/emotion regulation training intervention was designed by experts in contemplative traditions and emotion science to reduce "destructive enactment of emotions" and enhance prosocial responses. Participants were 82 healthy female schoolteachers who were randomly assigned to a training group or a wait-list control group, and assessed preassessment, postassessment, and 5 months after training completion. Assessments included self-reports and experimental tasks to capture changes in emotional behavior. The training group reported reduced trait negative affect, rumination, depression, and anxiety, and increased trait positive affect and mindfulness compared to the control group. On a series of behavioral tasks, the training increased recognition of emotions in others (Micro-Expression Training Tool), protected trainees from some of the psychophysiological effects of an experimental threat to self (Trier Social Stress Test; TSST), appeared to activate cognitive networks associated with compassion (lexical decision procedure), and affected hostile behavior in the Marital Interaction Task. Most effects at postassessment that were examined at follow-up were maintained (excluding positive affect, TSST rumination, and respiratory sinus arrhythmia recovery). Findings suggest that increased awareness of mental processes can influence emotional behavior, and they support the benefit of integrating contemplative theories/practices with psychological models and methods of emotion regulation.

Psychobiological responses to social threat: evolution of a psychological model in psychoneuroimmunology.

There exists a bidirectional network of interactions between the central nervous system, the endocrine system and the immune system. The existence of these pathways allows stressful life experience to impact the immune system with important implications for health. One powerful elicitor of changes in the autonomic, endocrine and immune systems is threat to social status. This review describes the development of a human model of social status threat that specifies a set of contextual, psychological and biological pathways that may underlie the health consequences of threats to social status and regard. The role of cognitive processes in shaping the physiological response to the social world will be emphasized.

Understanding the interaction between psychosocial stress and immune-related diseases: a stepwise progression.

For many years, anecdotal evidence and clinical observations have suggested that exposure to psychosocial stress can affect disease outcomes in immune-related disorders such as viral infections, chronic autoimmune diseases and tumors. Experimental evidence in humans supporting these observations was, however, lacking. Studies published in the last 2 decades in Brain, Behavior and Immunity and other journals have demonstrated that acute and chronic psychological stress can induce pronounced changes in innate and adaptive immune responses and that these changes are predominantly mediated via neuroendocrine mediators from the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal axis. In addition, psychological stress has predicted disease outcomes using sophisticated models such as viral challenge, response to vaccination, tracking of herpesvirus latency, exploration of tumor metastasis and healing of experimental wounds, as well as epidemiological investigations of disease progression and mortality. These studies have contributed significantly to our understanding that the neuroendocrine-immune interaction is disturbed in many pathophysiological conditions, that stress can contribute to this disturbance, and that malfunction in these communication pathways can play a significant role in the progression of disease processes. There are, however, significant gaps in the extant literature. In the coming decade(s), it will be essential to further analyze neuroendocrine-immune communication during disease states and to define the specific pathways linking the central nervous system to the molecular events that control important disease-relevant processes. This knowledge will provide the basis for new therapeutic pharmacological and non-pharmacological behavioral approaches to the treatment of chronic diseases via specific modulation of nervous system-immune system communication.

Immunological effects of induced shame and guilt.

OBJECTIVE: To determine if inducing self-blame would lead to increases in shame and guilt as well as increases in proinflammatory cytokine activity and cortisol. Based on previous research and theory, it was hypothesized that induced shame would be specifically associated with elevations in proinflammatory cytokine activity. MATERIALS AND METHODS: Healthy participants were randomly assigned to write about traumatic experiences in which they blamed themselves (N = 31) or neutral experiences (N = 18) during three 20-minute experimental laboratory sessions over 1 week. Tumor necrosis factor-alpha receptor levels (sTNFalphaRII), an indicator of proinflammatory cytokine activity, beta2-microglobulin, cortisol (all obtained from oral fluids), and emotion were assessed prewriting and postwriting. RESULTS: Participants in the self-blame condition showed an increase in shame and guilt as well as an increase in sTNFalphaRII activity when compared with those in the control condition. Cortisol and beta2-microglobulin levels were unaffected by the procedures. Those individuals in the self-blame condition reporting the greatest increases in shame in response to the task showed the greatest elevations in proinflammatory cytokine activity, while levels of guilt and general negative emotion were unrelated to cytokine changes. CONCLUSION: These data suggest that inducing self-related emotions can cause changes in inflammatory products, and that shame may have specific immunological correlates.

An interdisciplinary research model to investigate psychosocial cofactors in disease: Application to HIV-1 pathogenesis.

This paper argues for a broader interdisciplinary conceptualization of research on psychosocial risk factors and disease that relies on epidemiology, human laboratory-based studies, animal studies, in vitro and other mechanistic studies and intervention research. A model is proposed that includes the isolation of the active ingredients in the proposed psychological or social contributing factor, and a determination of their neural substrates, peripheral neurophysiological and pathophysiological correlates, and clinical disease outcomes. Research in HIV-1 pathogenesis provides examples of these kinds of studies. The HIV section highlights research that focuses on specific cognitive representations of stressful life experiences as active ingredients that shape the affective and neurophysiological impact of events. Links between these cognitive states and HIV progression, as well as the potential neurophysiologic, virologic, and immunologic mediators of these relationships are described. Implications and extensions of this model are derived for research on psychosocial factors and cancer.