Mark L. Laudenslager

On the physiology of grooming in a pigtail macaque

Several functions of social grooming have been proposed, including building affiliative bonds between group members, and reducing tension or anxiety. In this case study, heart rate (HR) of a single adult female pigtail macaque living in a social group was monitored in several behavioral contexts to examine the relationship between grooming and HR level, an indicator of autonomic nervous system activity. The subject was implanted as a part of another study with a multichannel telemetry system which monitored several physiological variables. Physiological and behavioral data were collected over a nine day period. Heart rate during agonistic interactions was significantly higher than during other categories of behavior, and sleep HR significantly lower. When the subject received grooming from others, HR was significantly lower than during self grooming or initiating grooming to others, as well as during other behaviors. HR showed significant declines during bouts of receiving groom (up to 20 bpm), but not during bouts of initiating or self grooming. Following aggression, HR decline was greatest while receiving grooming. There were also HR differences for methods of grooming: stroking but not other methods related to decreases in HR.

Hair cortisol levels as a retrospective marker of hypothalamic-pituitary axis activity throughout pregnancy: comparison to salivary cortisol.

Maternal stress during pregnancy is associated with negative maternal/child outcomes. One potential biomarker of the maternal stress response is cortisol, a product of activity of the hypothalamic-pituitary-adrenal axis. This study evaluated cortisol levels in hair throughout pregnancy as a marker of total cortisol release. Cortisol levels in hair have been shown to be easily quantifiable and may be representative of total cortisol release more than single saliva or serum measures. Hair cortisol provides a simple way to monitor total cortisol release over an extended period of time. Hair cortisol levels were determined from each trimester (15, 26 and 36 weeks gestation) and 3 months postpartum. Hair cortisol levels were compared to diurnal salivary cortisol collected over 3 days (3 times/day) at 14, 18, 23, 29, and 34 weeks gestational age and 6 weeks postpartum from 21 pregnant women. Both salivary and hair cortisol levels rose during pregnancy as expected. Hair cortisol and diurnal salivary cortisol area under the curve with respect to ground (AUCg) were also correlated throughout pregnancy. Levels of cortisol in hair are a valid and useful tool to measure long-term cortisol activity. Hair cortisol avoids methodological problems associated with collection other cortisol measures such as plasma, urine, or saliva and is a reliable metric of HPA activity throughout pregnancy reflecting total cortisol release over an extended period.

Reduced serum antibodies associated with social defeat in rats

Many studies have linked various physical stressors with changes in immune function. The present experiment examined the effect of a social stressor, defeat associated with territorial defense, on serum antibodies to a specific protein, keyhole limpet hemocyanin (KLH). Pairs of male rats formed colonies and experimental rats were intruders. Experimental animals were immunized with KLH prior to exposures to territorially defensive colonies. Control animals were placed into colonies but separated from residents by a Plexiglas barrier. Behavioral measures, including number of bites and total time spent in submissive postures, were taken for colony-intruder interactions. Serum antibody levels were determined from blood samples taken one, two, and three weeks following immunization. Experimental animals had significantly less serum antibodies to KLH than did controls. Within the experimental group, total time spent in submissive postures at week one was significantly correlated with serum antibody levels, such that animals spending the most time in submission had lower antibody levels. Total bites correlated only slightly with antibody levels. The correlation between submission and serum antibody levels increased when the bites factor was partialled out. A stressful social encounter may thus affect immune function in a manner independent of the influence of physical (nociceptive) stressors.

Suppressed immune response in infant monkeys associated with maternal separation

The effect of maternal separation on an in vitro measure of the cellular immune response was studied in infant bonnet monkeys (Macaca radiata). Using a modified mixed-species separation paradigm, bonnet mother-infant pairs were each housed with a single adult female pigtailed monkey (Macaca nemestrina). Over a 14-day separation period, the infants showed a suppression of lymphocyte proliferation in response to mitogens relative to a 14-day baseline period which preceded separation. The lymphocyte response was restored following reunion. During separation, infants were initially agitated, and this was followed by observations of reduced activity and a slouched posture. Behaviors returned to baseline conditions following reunion. It was concluded that suppressed immunological functioning may be included among the pathophysiological consequences of maternal separation in infant monkeys.

Diurnal rhythm of cortisol during late pregnancy: Associations with maternal psychological well-being and fetal growth

Maternal psychological functioning during pregnancy affects both maternal and fetal well-being. The hypothalamic-pituitary-adrenal (HPA) axis provides one mechanism through which maternal psychosocial factors may be transduced to the fetus. However, few studies have examined maternal psychological factors or birth outcomes in relation to the diurnal pattern of cortisol across the day. The current study examined maternal psychological well-being, parity status, and birth weight in relation to the maternal cortisol diurnal rhythm in a group of 98 low-risk pregnant women (51 primiparae). At 36 weeks gestation, participants completed both pregnancy-specific and general self-report measures of psychological functioning and provided saliva samples at 8:00, 12:00, and 16:00 h on 2 consecutive working days for the assay of cortisol. The expected diurnal decline in salivary cortisol was observed. Higher trait anxiety was associated with a flatter afternoon decline for all mothers. For primiparae, steeper morning cortisol declines were associated with lower infant birth weight. The findings suggest that regulation of the HPA axis may differ by parity status with downstream implications for fetal growth and development.

Suppression of specific antibody production by inescapable shock: Stability under varying conditions

The effect of exposure to uncontrollable shock on the production of antibodies to a novel antigen, keyhole limpet hemocyanin (KLH), was studied in adult male Sprague-Dawley rats. Groups of rats were tested under one of four experimental conditions which included testing during either the light or dark portions of their light cycles and following either one or three daily exposures to tail shock. Control subjects were immunized with KLH in the absence of shock exposure during either the light or dark phases of their light cycle. A tertiary (memory) response was evoked 60 days following the initial immunization sequence in all animals in the absence of a shock exposure. Blood samples were obtained from the tip of the tail at the time of each immunization and at 1-week intervals for 3 weeks following immunizations. Specific IgG antibodies to KLH were determined by an enzyme-linked immunosorbent assay (ELISA). All animals exposed to shock showed reduced levels of IgG antibodies to KLH regardless of the experimental conditions of shock exposure. Antibody levels were highest among animals immunized during the dark phase of their cycle for both control and shocked animals. Antibody production to a novel antigen appears to be a robust and sensitive measure for studies of modulation of immunity by behavioral factors.

Self-compassion training modulates alpha-amylase, heart rate variability, and subjective responses to social evaluative threat in women.

A growing body of research has revealed that social evaluative stressors trigger biological and psychological responses that in chronic forms have been linked to aging and disease. Recent research suggests that self-compassion may protect the self from typical defensive responses to evaluation. We investigated whether brief training in self-compassion moderated biopsychological responses to the Trier Social Stress Test (TSST) in women. Compared to attention (placebo) and no-training control conditions, brief self-compassion training diminished sympathetic (salivary alpha-amylase), cardiac parasympathetic, and subjective anxiety responses, though not HPA-axis (salivary cortisol) responses to the TSST. Self-compassion training also led to greater self-compassion under threat relative to the control groups. In that social stress pervades modern life, self-compassion represents a promising approach to diminishing its potentially negative psychological and biological effects.

Elevated cytotoxicity in combat veterans with long-term post-traumatic stress disorder: preliminary observations.

Resting immune [WBC and differential cell counts lymphocyte phenotyping (CD2, CD4, CD8, CD16, CD20, and CD56), and NK activity] and endocrine (cortisol, prolactin, growth hormone, and DHEA-SO4) parameters were measured in 10 male, Vietnam combat veterans diagnosed with long-term post-traumatic stress disorder (PTSD) and 9 control Vietnam combat veterans without a PTSD diagnosis but with a comparable history of alcohol abuse. Subjects completed a battery of psychological questionnaires. We report on preliminary observations of the relationship between PTSD and physiological and psychological parameters. With some important exceptions, PTSD patients did not differ from the age-matched control group with regard to hormone levels or lymphocyte phenotypes. However, NK activity was higher in the PTSD population than in the controls. Beck, Mississippi, and Combat Exposure scores were significantly elevated in the PTSD population. In contrast to previous observations in depressed populations, depression (indicated by elevated Beck scores), comorbid with PTSD, was associated with increased natural cytotoxicity.

Heritability and genetic correlation of hair cortisol in vervet monkeys in low and higher stress environments

Chronic activation of the hypothalamic-pituitary adrenal (HPA) system is a risk factor for a variety of physical and mental disorders, and yet the complexity of the system has made it difficult to define the role of genetic and environmental factors in producing long-term individual differences in HPA activity. Cortisol levels in hair have been suggested as a marker of total HPA activation over a period of several months. This study takes advantage of a pedigreed nonhuman primate colony to investigate genetic and environmental influences on hair cortisol levels before and after an environmental change. A sample of 226 adult female vervet monkeys (age 3-18) living in multigenerational, matrilineal social groups at the Vervet Research Colony were sampled in a stable low stress baseline environment and 6 months after the entire colony was moved to a new facility with more frequent handling and group disturbances (higher stress environment). Variance components analysis using the extended colony pedigree was applied to determine heritability of hair cortisol levels in the two environments. Bivariate genetic correlation assessed degree of overlap in genes influencing hair cortisol levels in the low and higher stress environments. The results showed that levels of cortisol in hair of female vervets increased significantly from the baseline to the post-move environment. Hair cortisol levels were heritable in both environments (h(2)=0.31), and there was a high genetic correlation across environments (rhoG=0.79), indicating substantial overlap in the genes affecting HPA activity in low and higher stress environments. This is the first study to demonstrate that the level of cortisol in hair is a heritable trait. It shows the utility of hair cortisol as a marker for HPA activation, and a useful tool for identifying genetic influences on long term individual differences in HPA activity. The results provide support for an additive model of the effects of genes and environment on this measure of long term HPA activity.

Inflammatory and hormonal measures predict neuropsychological functioning in systemic lupus erythematosus and rheumatoid arthritis patients.

Abnormalities of inflammatory and hormonal measures are common in SLE patients. Although cognitive dysfunction has been documented in SLE patients, the biological mechanism of these deficits has not been clarified. The goal of this study was to explore the relationship between inflammatory and hormonal activity and measures of learning, fluency, and attention in systemic lupus erythematosus patients without neuropsychiatric symptoms (non-CNS-SLE), patients with rheumatoid arthritis (RA), and healthy controls (HC). Fifteen non-CNS-SLE patients, 15 RA patients and 15 HC participants similar in age, education, and gender (female) were compared on tests of cognition, depression, and plasma levels of interleukin-6 (IL-6), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S) and cortisol. Non-CNS-SLE patients demonstrated lower learning and poorer attention. Furthermore, non-CNS-SLE and RA patients had significantly lower levels of DHEA and DHEA-S than HC participants. Hierarchical regression analysis demonstrates that DHEA-S and IL-6 accounts for a unique portion of the variance in subject performance on measures of learning and attention after controlling for depression and corticosteroid treatment. This data highlights the value of hierarchical analyses with covariates, and provides evidence in humans of a relationship between peripheral cytokine levels and cognitive function.