Dettmer AM, Novak MA, Suomi SJ, Meyer JS. Physiological and behavioral adaptation to relocation stress in differentially reared rhesus monkeys: hair cortisol as a biomarker for anxiety-related responses. Psychoneuroendocrinology 37: 191-199

Department of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA 15213, USA.
Psychoneuroendocrinology (Impact Factor: 4.94). 06/2011; 37(2):191-9. DOI: 10.1016/j.psyneuen.2011.06.003
Source: PubMed


Increased hair cortisol concentrations have been associated with stress exposure in both human and nonhuman primates, and hair cortisol is now gaining attention as a biomarker for stress-related health problems. The present study examined the behavioral and physiological reactions of rhesus monkey (Macaca mulatta) infants reared in three different rearing environments to the major stressor of relocation. Infant monkeys (n=61) were studied from birth through 2 years of age. For the first 8 months of life, infants were either with their mothers and peers (MPR, n=21) or reared in a nursery using either peer-rearing (PR, n=20) or surrogate-peer-rearing (SPR, n=20). At approximately 8 months of age, infants were removed from their rearing group, simultaneously placed into a large social environment consisting of infants from all three rearing conditions, and observed for the next 16 months. Behavior was recorded twice per week from 1 to 24 months, and composite anxiety scores were calculated for each monkey. Monkeys were initially shaved at the nape of the neck on day 14 to remove any prenatal effects on hair cortisol deposition. Hair samples were then collected by re-shaving at 6, 12, 18 and 24 months and analyzed for cortisol content. MPR monkeys were the least affected by the stressor, showing smaller increases in anxious behavior than the other groups and more rapid physiological adaptation as assessed using hair cortisol. PR monkeys showed heightened and prolonged anxious behavior, had the highest cortisol levels prior to relocation, and their cortisol levels did not decline until more than a year later. SPR monkeys exhibited more rapid behavioral adaptation than PR monkeys, showing heightened but not prolonged anxious behavior. However, the SPR group showed a marked increase in cortisol in response to the relocation, and like the PR group, their physiological adaptation was slower than that of the MPR group as indicated by elevated cortisol levels at 18 months. By 24 months of age (16 months after relocation), all rearing groups were indistinguishable from one another physiologically and behaviorally. Spearman rank correlation revealed that hair cortisol taken at month 6 was not correlated with composite anxiety scores from months 6 to 8 (just before the relocation), but was positively correlated with composite anxiety scores between months 8 and 12 (immediately after relocation) for PR infants only (r(s)=0.75, p<0.001). Month 6-hair cortisol tended to positively correlate with composite anxiety scores for the following 6 months (months 12-18) for PR monkeys only (r(s)=0.47, p=0.037), which exhibited more anxious behavior than MPR and SPR infants during this period (ANOVA: F((2,60))=14.761, p<0.001) This is the first study to show that elevated hair cortisol early in life is a biomarker for the later development of anxious behavior in response to a major life stressor, particularly for infant monkeys exposed to early life adversity in the form of peer-rearing.

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    • "The few studies examining SPR monkeys have demonstrated more anxious behavior, especially in the form of self-directed behavior by these monkeys in social settings, than in MPR monkeys but less anxiety than PR monkeys, especially after novel group formation (Dettmer et al. 2012; Strand et al. 2005). Additionally, nursery-reared monkeys collectively exhibit dysregulated hypothalamic-pituitaryadrenal axis activity in response to separation and novel situations compared with MPR monkeys (Capitanio et al. 2005; Clarke 1993; Dettmer et al. 2012; Higley and Suomi 1989; Higley et al. 1992; Higley, Suomi, Linnoila 1991; Shannon et al. 1998). "
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    ABSTRACT: This report reviews the scientific literature from the past several decades that focuses on nonhuman primates (NHPs) as models of neuropsychiatric disorders, including anxiety, and alcoholism. In particular, we highlight the approaches, advantages, and disadvantages of the rearing, genetic, and epigenetic methodologies behind these studies as a means of evaluating the application of these methods in assessing disorders in NHPs as models of human disease. Finally, we describe the contributions the NHP studies have made to neuropsychiatric research and areas for future research.
    ILAR journal / National Research Council, Institute of Laboratory Animal Resources 09/2014; 55(2):361-70. DOI:10.1093/ilar/ilu025 · 2.39 Impact Factor
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    • "In non-human primates, while results are not entirely consistent (Dettmer et al., 2012), early social deprivation appears to down-rather than up-regulate the HPA axis (Meyer et al., 1975; Clarke, 1993; Cirulli et al., 2009). This was confirmed recently in a large study of Rhesus macaques (Hawkley et al., 2012). "
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    ABSTRACT: Growing evidence suggests that early social deprivation impacts the activity of the hypothalamic-pituitary-adrenocortical axis. Early adverse care in the form of institutional or orphanage care provides a human model for early social deprivation. The present study examined changes in diurnal cortisol during the transition to family care in the first 2 years post-adoption. Children adopted between 15 and 36 months from institutional care were examined four times during their first 2 years post-adoption (N=58). Comparison groups included same-aged peers reared in their birth families (N=50) and children adopted during their first year from overseas foster care (N=47). Children provided daily cortisol samples at roughly 2, 9, 17, and 25 months post-adoption. Post-institutionalized and post-foster care children exhibited less steep diurnal cortisol compared to non-adopted same-aged peers; these differences did not diminish across the 2 year period. For post-institutionalized children, lower social care quality in institutions was associated with less steep cortisol slopes. Lastly, shallower diurnal cortisol was a mediator between adoption status and increased behavioral problems 2 years post-adoption. Consistent with the non-human primate literature, early social deprivation may contribute to early programming of the HPA axis.
    Psychoneuroendocrinology 08/2014; 50C:1-13. DOI:10.1016/j.psyneuen.2014.07.028 · 4.94 Impact Factor
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    • " placed in an aluminum foil pouch and stored in the dark at room temperature until assay , which occurred within 1 month of hair collection ( Davenport et al . , 2006 ; Dettmer et al . , 2012 ) . Our labora - tory validated , and has since published numerous studies on , the hair cortisol assay in rhesus monkeys ( Davenport et al . , 2006 , 2008 ; Dettmer et al . , 2009 , 2012 ) and other animals ( Bechshøft et al . , 2011 ) . Briefly , hair samples were weighed , washed twice with isopropanol , allowed to air dry for 5—7 days , then ground to a fine powder with a ball mill grinder ( MM200 ; Retsch , Newtown , PA ) before being incubated in methanol for 24 hr to extract cortisol from the samples ."
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    ABSTRACT: Population density is known to influence acute measures of hypothalamic-pituitary-adrenal (HPA) axis activity in a variety of species, including fish, deer, birds, and humans. However, the effects of population density on levels of chronic stress are unknown. Given the fact that exposure to chronically elevated levels of circulating glucocorticoids results in a host of health disparities in animals and humans alike, it is important to understand how population density may impact chronic stress. We assessed hair cortisol concentrations (HCCs), which are reliable indicators of chronic HPA axis activity, in rhesus monkeys (Macaca mulatta) to determine the influence of population density on these values. In Experiment 1, we compared HCCs of monkeys living in high-density (HD; 1 monkey/0.87 m2) and low-density (LD; 1 monkey/63.37 m2) environments (N = 236 hair samples) and found that HD monkeys exhibited higher hair cortisol across all age categories (infant, juvenile, young adult, adult, and aged) except infancy and aged (F(5) = 4.240, p = 0.001), for which differences were nearly significant. HD monkeys also received more severe fight wounds than LD monkeys (χ2 = 26.053, p < 0.001), though no effects of dominance status emerged. In Experiment 2, we examined how HCCs change with fluctuating population levels across five years in the adult LD monkeys (N = 155 hair samples) and found that increased population density was significantly positively correlated with HCCs in this semi-naturalistic population (r(s) = 0.975, p = 0.005). These are the first findings to demonstrate that increased population density is associated with increased chronic, endogenous glucocorticoid exposure in a nonhuman primate species. We discuss the implications of these findings with respect to laboratory research, population ecology, and human epidemiology.
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