William B. Malarkey

Loneliness and health: potential mechanisms.

Objective Two studies using cross-sectional designs explored four possible mechanisms by which loneliness may have deleterious effects on health: health behaviors, cardiovascular activation, cortisol levels, and sleep. Methods In Study 1, we assessed autonomic activity, salivary cortisol levels, sleep quality, and health behaviors in 89 undergraduate students selected based on pretests to be among the top or bottom quintile in feelings of loneliness. In Study 2, we assessed blood pressure, heart rate, salivary cortisol levels, sleep quality, and health behaviors in 25 older adults whose loneliness was assessed at the time of testing at their residence. Results Total peripheral resistance was higher in lonely than nonlonely participants, whereas cardiac contractility, heart rate, and cardiac output were higher in nonlonely than lonely participants. Lonely individuals also reported poorer sleep than nonlonely individuals. Study 2 indicated greater age-related increases in blood pressure and poorer sleep quality in lonely than nonlonely older adults. Mean salivary cortisol levels and health behaviors did not differ between groups in either study. Conclusions Results point to two potentially orthogonal predisease mechanisms that warrant special attention: cardiovascular activation and sleep dysfunction. Health behavior and cortisol regulation, however, may require more sensitive measures and large sample sizes to discern their roles in loneliness and health.

Negative Behavior During Marital Conflict Is Associated With Immunological Down-Regulation

&NA; Although increased morbidity and mortality have been reliably associated with social isolation and less satisfying personal relationships, relatively little is known about the underlying biopsychosocial mechanisms. We assessed problem‐solving behaviors and changes in immune function in 90 newlywed couples who were admitted to a hospital research unit for 24 hours. Subjects who exhibited more negative or hostile behaviors during a 30‐minute discussion of marital problems showed greater decrements over 24 hours relative to low negative subjects on four functional immunological assays (natural killer cell lysis, blastogenic response to two mitogens, and the proliferative response to a monoclonal antibody to the T3 receptor), as well as larger increases in the numbers of total T lymphocytes and helper T lymphocytes. High negative subjects had higher antibody titers to latent Epstein‐Barr virus than low negative subjects, consistent with down‐regulated immune function. Women were more likely to show negative immunological changes than men. The discussion of marital problems also led to larger increases in blood pressure that remained elevated longer in high negative subjects than low negative subjects. Positive or supportive problem‐solving behaviors were not related to either immunological or blood pressure changes. These physiological differences were particularly noteworthy because marital satisfaction was high in both groups, and couples had been selected on the basis of stringent mental and physical health criteria. These data provide additional support for the link between personal relationships and immune function.

Stress-Induced Modulation of the Immune Response to Recombinant Hepatitis B Vaccine

&NA; Each of a series of three hepatitis B (Hep B) inoculations was given to 48 second‐year medical students on the 3rd day of a 3‐day examination series to study the effect of academic stress on the ability to generate an immune response to a primary antigen. Those students who seroconverted after the first injection (25%) were significantly less stressed and anxious than those who did not seroconvert at that time. In addition, students who reported greater social support demonstrated a stronger immune response to the vaccine at the time of the third inoculation, as measured by antibody titers to Hep B surface antigen (HBsAg) and the blastogenic response to a HBsAg peptide (SAg).

Studying Multivariate Change Using Multilevel Models and Latent Curve Models

In longitudinal research investigators often measure multiple variables at multiple points in time and are interested in investigating individual differences in patterns of change on those variables. In the vast majority of applications, researchers focus on studying change in one variable at a time. In this article we consider methods for studying relations1.1ips between patterns of change on different variables. We show how the multilevel modeling framework, which is often used to study univariate change, can be extended to the multivariate case to yield estimates of covariances of parameters representing aspects of change on different variables. We illustrate this approach using data from a study of physiological response to marital conflict in older married couples, showing a substantial correlation between rate of linear change on different stress-related hormones during conflict. We also consider how similar issues can be studied using extensions of latent curve models to the multivariate case, and we show how such models are related to multivariate multilevel models.

Lonely traits and concomitant physiological processes : the MacArthur social neuroscience studies

Loneliness is a complex set of feelings encompassing reactions to unfulfilled intimate and social needs. Although transient for some individuals, loneliness can be a chronic state for others. Prior research has shown that loneliness is a major risk factor for psychological disturbances and for broad-based morbidity and mortality. We examined differences between lonely and socially embedded individuals that might explain differences in health outcomes. Satisfying social relationships were associated with more positive outlooks on life, more secure attachments and interactions with others, more autonomic activation when confronting acute psychological challenges, and more efficient restorative behaviors. Individuals who were chronically lonely were characterized by elevated mean salivary cortisol levels across the course of a day, suggesting more discharges of corticotropin-releasing hormone and elevated activation of the hypothalamic-pituitary-adrenocorticol axis. An experimental manipulation of loneliness further suggested that the way in which people construe their self in relation to others around them has powerful effects on their self concept and, possibly, on their physiology.

Childhood Adversity Heightens the Impact of Later-Life Caregiving Stress on Telomere Length and Inflammation

Objective: To address the question of whether childhood abuse and other adversities have lasting, detectable consequences for inflammation and cell aging late in life, and whether the effects are large enough to be discernible beyond that of a major chronic stressor, dementia family caregiving. Previous research on the physical health consequences of childhood abuse and other adversities has been based on data from young or middle-aged adults. Method: In this community sample of 132 healthy older adults (mean age = 69.70 years; standard deviation = 10.14), including 58 dementia family caregivers and 74 noncaregivers, blood samples were analyzed for interleukin (IL)-6, tumor necrosis factor (TNF)-&agr;, and telomere length, a measure of cell aging. Depressive symptoms were assessed by the Center for Epidemiological Studies Depression Scale. Results: After controlling for age, caregiving status, gender, body mass index, exercise, and sleep, the presence of multiple childhood adversities was related to both heightened IL-6 (0.37 ± 0.03 log10 pg/mL versus 0.44 ± 0.03 log10 pg/mL) and shorter telomeres (6.51 ± 0.17 Kb versus 5.87 ± 0.20 Kb), compared with the absence of adversity; the telomere difference could translate into a 7- to 15-year difference in life span. Abuse was associated with heightened IL-6 and TNF-&agr; levels; for TNF-&agr;, this relationship was magnified in caregivers compared with controls. Moreover, abuse and caregiving status were associated significantly and independently with higher levels of depressive symptoms. Conclusions: Adverse childhood events are related to continued vulnerability among older adults, enhancing the impact of chronic stressors. Childhood adversities cast a very long shadow. BMI = body mass index; CES-D = Center for Epidemiological Studies Depression Scale; CRP = C-reactive protein; IL = interleukin; PBMCs = peripheral blood mononuclear cells; TNF = tumor necrosis factor.

Octreotide Treatment of Acromegaly: A Randomized, Multicenter Study

OBJECTIVE To determine the effects of the somatostatin analog, octreotide acetate, in patients with acromegaly. DESIGN Double-blind, randomized trial. SETTING Fourteen university-affiliated medical centers. PATIENTS One hundred fifteen acromegalic patients, 70% of whom had persistent disease after pituitary surgery or radiotherapy. INTERVENTION Subcutaneous octreotide, 100 micrograms, or placebo every 8 hours for 4 weeks. Four weeks after the end of treatment, patients were randomized to receive 100 or 250 micrograms octreotide subcutaneously every 8 hours for 6 months. RESULTS After 2 weeks of treatment, a single 100-micrograms injection reduced mean serum growth hormone (GH) to 30% of the pretreatment concentration within 2 hours. The integrated mean GH level was reduced over 8 hours from 39 +/- 11 micrograms/L to 9 +/- 2 micrograms/L (P less than 0.001). Mean plasma insulin-like growth factor-1 (IGF-1) was reduced from 5100 +/- 400 U/L to 2400 +/- 400 U/L (P less than 0.001). After 6 months, the mean GH was reduced from 39 +/- 13 to 15 +/- 4 micrograms/L by 300 micrograms of octreotide and from 29 +/- 5 micrograms/L to 9 +/- 2 micrograms/L by 750 micrograms of octreotide daily. The mean IGF-1 concentration was suppressed to 2100 +/- 300 and 2500 +/- 400 U/L after 300 and 750 micrograms octreotide, respectively. Integrated mean GH levels were reduced to < 5 micrograms/L in 53% (95% CI, 39% to 67%) and 49% (CI, 35% to 63%), and IGF-1 levels were normal in 68% (CI, 54% to 82%) and 55% (CI, 40% to 70%) of patients receiving low- and high-dose octreotide, respectively. A substantial decrease in headache, amount of perspiration, joint pain, and finger circumference occurred in two thirds of the patients. The pituitary size was reduced in 19% (CI, 5% to 33%) and 37% (CI, 22% to 52%) of patients receiving 6 months of low- and high-dose octreotide, respectively. Ten percent and 13% of patients in each treatment group developed transient diarrhea; 10% and 14%, biliary sludge; and 6% and 18%, cholelithiasis, respectively. CONCLUSION Octreotide effectively decreased GH and IGF-1 concentrations in 53% and 68% of patients, respectively. The higher dose resulted in increased frequency of tumor shrinkage but added no biochemical or clinical benefit.

Chronic Stress Modulates the Immune Response to a Pneumococcal Pneumonia Vaccine

Objective Influenza and pneumonia account for significant morbidity and mortality, particularly in older individuals. Previous studies have shown that spousal caregivers of patients with dementia have poorer antibody and virus specific T cell responses to an influenza virus vaccine relative to noncaregiving control subjects. This study tested the hypothesis that stress can also significantly inhibit the IgG antibody response to a pneumococcal bacterial vaccine. Method We measured antibody titers of current caregivers, former caregivers, and control subjects after vaccination with a pneumococcal bacterial vaccine. Results Caregivers showed deficits relative to controls and former caregivers in their antibody responses to vaccination. Although the groups did not differ before vaccination or in the rise in antibody 2 weeks or 1 month after vaccination, current caregivers had lower antibody titers 3 and 6 months after vaccination than either former caregivers or controls. Conclusions These data, the first evidence that chronic stress can inhibit the stability of the IgG antibody response to a bacterial vaccine for pneumonia, provide additional evidence of health risks associated with dementia caregiving.

Heterogeneity in Neuroendocrine and Immune Responses to Brief Psychological Stressors as a Function of Autonomic Cardiac Activation

Human responses to brief psychological stressors are characterized by changes and large individual differences in autonomic, neuroendocrine, and immune function.The authors examined the effects of brief psychological stressors on cardiovascular, neuroendocrine, and cellular immune response in 22 older women to investigate the common effects of stress across systems. They also used interindividual variation in heart rate reactivity, cardiac sympathetic reactivity (as indexed by preejection period reactivity in their reactivity paradigm), and cardiac vagal reactivity (as indexed by respiratory sinus arrhythmia reactivity) to explore the heterogeneity in human responses to brief psychilogical stressors. The results revealed that brief psychological stressors heightened cardiac activation, elevated plasma catecholamine concentrations, and affected the cellular immune response. It was also found that individuals characterized by high, relative to low, cardiac sympathetic reactivity showed higher stress-related changes in adrenocorticotropic hormone and cortisol plasma levels but comparable changes in epinephrine and norepinephrine concentrations. These data suggest that the effects of psychological stressors on cardiovascular and cellular immune response are governed by coordinated regulatory mechanism(s) and that going beyond the simple notion of heart rate reactivity to examine neural substrates may shed light on the interrelationships among and the regulatory mechanisms for the autonomic, endocrine, and immune responses to stressors.

Effects of Low-Dose Mindfulness-Based Stress Reduction (MBSR-ld) on Working Adults

Mindfulness-based stress reduction (MBSR) has produced behavioral, psychological, and physiological benefits, but these programs typically require a substantial time commitment from the participants. This study assessed the effects of a shortened (low-dose [ld]) work-site MBSR intervention (MBSR-ld) on indicators of stress in healthy working adults to determine if results similar to those obtained in traditional MBSR could be demonstrated. Participants were randomized into MBSR-ld and wait-list control groups. Self-reported perceived stress, sleep quality, and mindfulness were measured at the beginning and end of the 6-week intervention. Salivary cortisol was assessed weekly. Significant reductions in perceived stress (p = .0025) and increases in mindfulness (p = .0149) were obtained for only the MBSR-ld group (n = 22). Scores on the global measure of sleep improved for the MBSR-ld group (p = .0018) as well as for the control group (p = .0072; n = 20). Implications and future research are discussed.