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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    • "In addition, although hair sampling may require capture or handling in certain cases (with the exception of using barbed wire at bait stations; Mowat and Strobeck, 2000; Ausband et al., 2011), any stress experienced during this event would not impact glucocorticoid levels in the collected hair. For these reasons, hair has been explored in a number of mammalian species, including reindeer/ caribou (Rangifer tarandus; Ashley et al., 2011), grizzly bear (Ursus arctos; Macbeth et al., 2010) and rhesus monkey (Macaca mulatta; Dettmer et al., 2012), as an index of an animal's glucocorticoid production (hence, degree of physiological stress) over time. Although hair cortisol concentration is increasingly being used for the assessment of physiological stress over long time periods in a number of contexts, there has been little effort to validate the physiological or biological relevance of hair cortisol values and determine whether they reflect cortisol levels in the blood accurately. "
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    ABSTRACT: Stress levels of individuals are documented using glucocorticoid concentrations (including cortisol) in blood, saliva, urine or faeces, which provide information about stress hormones during a short period of time (minutes to days). In mammals, use of hair cortisol analysis allows for the assessment of prolonged stress over weeks and months and provides information on chronic stress levels without bias associated with handling. Here, we validate hair cortisol analysis in wild rodents using exogenous adrenocorticotrophic hormone (ACTH challenge) and apply the technique to evaluate stress in eastern chipmunks inhabiting logged and natural sites. Chipmunks were subjected to a mark–recapture study and injected weekly with ACTH (Synacthen Depot) or saline, with hair being collected at the conclusion of the challenge. Subsequently, faecal and hair samples were collected from chipmunks occupying logged and natural sites to assess the utility of hair cortisol in comparison with faecal cortisol metabolites. Following extraction, cortisol concentrations were quantified in hair and faecal extracts by enzyme immunoassay. Hair cortisol concentrations were significantly elevated in samples from ACTH-injected chipmunks compared with saline-injected control animals (five times higher). Chipmunks inhabiting logged sites had increased faecal cortisol metabolite concentrations compared with those in natural sites, but no differences were observed in hair cortisol concentrations. Faecal cortisol metabolite levels were positively correlated with hair cortisol levels in chipmunks. Hair cortisol levels reflect changes in circulating cortisol levels and can be used to evaluate the adrenal stress response, and thus stress, in natural populations. Nonetheless, because of the differences in the temporal scale of stress that hair and faeces represent, we caution the use of hair cortisol for detecting differences in physiological stress when comparing individuals within populations and suggest that it is best suited to examining population-level differences.
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    • "They are then housed in large mixed-rearing social groups consisting of 25 to 50 individuals. Although peer rearing and surrogate peer rearing monkeys exhibit species-typical behavior and appropriate parental behavior (Novak et al. 1992; Roma et al. 2006; see Sackett et al. 2002 for similar findings in pigtailed macaques), they show altered emotional regulation, which includes anxious behavior and higher levels of fear and aggression, as compared with maternally reared infants (Dettmer et al. 2012; Harlow and Harlow 1962). However, only the surrogate peer rearing condition is a significant predictor of SIB at this facility, occurring in 28% (n = 23 of 80) monkeys as compared with 0% (n = 0 of 84) in peer-reared monkeys and 1% (n = 2 of 181) in maternally reared monkeys (Lutz et al. 2007). "
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    ABSTRACT: Nonsuicidal self-injurious behavior occurs in the general human population, particularly among teenagers and young adults. Some rhesus macaques also develop self-injurious behavior (SIB) as adolescents or young adults. In both of these cases, the development of harmful behaviors is idiopathic, only coming to the attention of physicians or veterinarians after the disorder is established. Thus, a combination of retrospective, statistical, and empirical procedures are used to understand this disorder. Here, we identify concordances between macaques and humans across five different levels of analysis-(1) form and prevalence, (2) etiology, (3) triggering events, (4) function/maintenance, and (5) therapeutic intervention-and show the value of the cross-translational model (macaques to humans and humans to macaques) in understanding this phenomenon. Substantial concordance is present with respect to the range of severity, the presence of early life stress exposure, and emotional dysregulation. In the macaque model, additional information is available on the hypothalamic-pituitary-adrenal axis stress response system, possible genetic involvement, and the immediate contextual situations that appear to trigger or exacerbate SIB episodes. In contrast, considerably more information is available from human studies on the effectiveness of various treatment regimens. Veterinarians have drawn on this information to explore these therapeutic interventions in monkeys. We expect that models of SIB will continue to have cross-translational impact as scientists and practitioners move from preclinical to clinical research and treatment.
    Preview · Article · Sep 2014 · ILAR journal / National Research Council, Institute of Laboratory Animal Resources
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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.
    Full-text · Article · Sep 2014 · ILAR journal / National Research Council, Institute of Laboratory Animal Resources
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