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Personality characteristics and basal cortisol concentrations in adult male rhesus macaques (Macaca mulatta)
Psychoneuroendocrinology (2004) 29, 1300–1308
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Personality characteristics and basal cortisol concentrations in adult male rhesus macaques (Macaca mulatta) John P. Capitanioa,b,*, Sally P. Mendozaa,b, Kathleen L. Bentsonb,c a
Department of Psychology, University of California, Davis, CA, USA California National Primate Research Center, University of California, One Shields Avenue, Davis, CA 95616, USA c Washington National Primate Research Center, University of Washington, USA b
Received 29 October 2003; received in revised form 26 March 2004; accepted 2 April 2004
KEYWORDS Personality; Hormones; Cortisol; Circadian rhythm; Monkeys
Summary Although data show that psychosocial factors can regulate physiological processes, few data have been collected on normative populations. Studies in humans have suggested that personality characteristics might be related to regulation of the hypothalamic–pituitary–adrenal (HPA) axis. We explored the relationship between personality characteristics and plasma cortisol concentrations in adult male rhesus macaques. Two sets of blood samples were obtained from monkeys using a procedure with which they were very familiar; thus, cortisol concentrations reflected basal values. Analyses indicated high-excitable animals had lower basal cortisol concentrations during the afternoon period, and that low-confidence was associated with lower cortisol in the morning period, and lack of a circadian decline in the afternoon period. Sociability and equability were unrelated to cortisol levels. Our data confirm and extend some results found in human studies, and suggest that even in normal populations, personality characteristics are related to measures of HPA function. We propose that comparative studies of personality in nonhuman primates that parallel studies in humans can increase our understanding of mechanisms whereby personality may relate to mental and physical health outcomes. # 2004 Elsevier Ltd. All rights reserved.
1. Introduction Personality is a major individual differences construct in psychology. Early theorizing about personality (e.g., Allport, 1937) identified many of the themes that have been elaborated upon in the * Corresponding author. Tel.: +1-530-752-4002; fax: +1-530752-2880. E-mail address: [email protected] (J.P. Capitanio).
last half century—the fact that personality comprises multiple dimensions (whether of traits or motives: Winter et al., 1998); that personality has a neural basis (e.g., Cloninger, 1986); and that personality is associated with physiological measures and health outcomes (e.g., Adler, 1994; Miller et al., 1999). While personality correlates of a number of physiological systems have been explored, particular interest has focused on hormones of the hypothalamic–pituitary–adrenal
0306-4530/$ - see front matter # 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.psyneuen.2004.04.001
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(HPA) axis, which is responsive to situations that engender psychological stress. Experimental research in animals, for example, has demonstrated that particular rearing conditions, which affect personality-related processes such as emotionality and responsiveness, also profoundly affect characteristics of the HPA axis (e.g., Levine, 2000). Similarly, research with humans has demonstrated that early adverse experiences such as sexual and emotional abuse also affect personality (e.g., Roy, 2002) and HPA function and regulation (e.g., Heim et al., 2000). While there is strong evidence that the HPA system is responsive to experimentally induced manipulations such as nursery- (as compared to mother-) rearing in monkeys, or to severe traumatic events such as the early experience of child abuse in humans, far less is known about how naturally occurring variation in characteristics of normal individuals might relate to HPA functioning. Studies of ‘‘normal’’ populations provide complementary information on the generality of a result found with clinical or extreme samples, allowing one to infer, for example, whether relationships are linear or curvilinear. Such studies also provide the basis for taking a ‘‘person-centered’’ approach to personality, where the focus is on identifying personality ‘‘types’’ that comprise relatively distinct subgroups of individuals that exhibit a clustering of traits (e.g., Hart et al., 2003). A good example of the typological approach is the work of Kagan and colleagues who have focused on early infant temperament. Children described as ‘‘inhibited’’ as infants—evidenced by long latencies to play, speak, and interact with unfamiliar individuals—have higher morning cortisol concentrations compared to uninhibited children at 5.5 years of age (Kagan et al., 1988), a result consistent with other data suggesting that inhibited children show greater physiological responsiveness. Only a few studies of normal populations of adult humans have focused on relationships between personality dimensions and HPA measures. Miller et al. (1999) reported small but significant correlations between morning plasma cortisol concentrations and the personality dimensions Extraversion and Neuroticism (r ¼ 0:17 and 0.18, n ¼ 276, respectively). No relationship was found between cortisol and agreeableness. In contrast, McCleery and Goodwin (2001) reported that young adults in the upper quartile for Neuroticism had a smaller increase in cortisol levels following a combined dexamethasone suppression/CRH stimulation test, compared to those in the lower quartile on Neuroticism. This result suggested to the authors that individuals high in Neuroticism
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may have enhanced glucocorticoid negative feedback sensitivity. Finally, basal salivary cortisol has been found to be negatively associated with Sensation Seeking (a personality dimension that reflects impulsivity) in one study (Rosenblitt et al., 2001). As part of a larger project examining the role that social factors play in endocrine and immune functioning in adult male rhesus macaques (e.g., Capitanio et al., 1998), we have had a secondary focus on how personality characteristics influence behavior and physiology. We have identified four personality dimensions (Capitanio, 1999)—Sociability, Confidence, Equability, and Excitability— though our principal interest has been with Sociability, which represents a tendency to affiliate (and which has been suggested as being similar to the human personality dimension Extraversion: Gosling and John, 1999). Our data have indicated that individual differences in Sociability predict behavioral and physiological functioning in situations that have social import to animals (Capitanio et al., 1999; Maninger et al., 2003). Our goal in the present report was twofold— first, to determine whether, in a situation that is decidedly nonsocial (repeated phlebotomy of animals while they are in their individual housing cages), Sociability would predict cortisol concentrations; and second, whether other aspects of primate personality, specifically Excitability, would affect cortisol levels. Despite the modest result reported in humans by Miller et al. (1999), we expected that Sociability would not be related to cortisol concentrations, inasmuch as this dimension is unlikely to contribute to the animals’ functioning in nonsocial situations. In contrast, Excitability appears to be a dimension reflecting overall emotional reactivity, and in fact has been likened to the human dimension of Neuroticism (Gosling and John, 1999). For example, when individually housed adult male rhesus monkeys are presented with a threatening human, scores on the dimension Excitability alone predict their behavioral response—more Excitable animals spend more time in the front of the cage nearest the human threatening him. Scores on the other dimensions did not predict behavioral responses in this situation (Capitanio, 1999). Excitability does contribute to responses in social situations as well, and seems to reflect generalized behavioral responsiveness, which is often manifested as combinations of aggressive, affiliative, and fearful behaviors, sometimes displayed in rapid succession. An earlier study, with a separate set of animals, indicated that Excitability was correlated positively with cortisol concentrations measured
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during a study involving social exposures (Capitanio et al., 1999). Thus, we predicted that highand low-Excitable animals might differ in cortisol concentrations in a nonsocial situation as well. The conflicting results for Neuroticism reported above for the human studies, however, suggested a two-tailed approach to this hypothesis. We did not have specific predictions for our other two personality dimensions, Equability (reflecting, perhaps, agreeableness) and Confidence (which correlates with aggressiveness in rhesus monkeys, and may be a species-specific composite dimension reflecting low agreeableness and Extraversion). Blood samples were taken from 16 adult male rhesus monkeys while they were in their familiar, individual living cages. The animals were subjects in a study designed to assess whether the anesthetic agents ketamine and Telazol affected cortisol concentrations during the 2 h following administration of the agent. These data have been published (Bentson et al., 2003). A third condition, saline injection, was also included as a control condition. In the present report, we examine how personality factors relate to cortisol concentrations during repeated blood sampling (a procedure with which the animals had considerable experience) during the 2 h following saline administration.
2. Methods 2.1. Subjects Subjects were 16 adult male rhesus monkeys (Macaca mulatta). All were born in half-acre corrals at the California National Primate Research Center, each comprising 60–100 animals with an age/sex structure approximating that found in feral troops. The subjects had lived in individual indoor cages (standard stainless steel cages equipped with squeeze-back mechanisms) for 5 years prior to the start of this study. Animals had participated in a series of studies examining behavioral and physiological responses in various social situations, but had not been on-project for more than a year prior to the start of the current study. Animals were, however, paired with a familiar partner in another room for 1–2 h periods several days per week. Animals were not socialized on the day of blood sampling. Each animal had been trained to cooperate during venipuncture, and each animal was very familiar with the procedure, having experienced sample collection via armpull at approximately monthly intervals during the previous 5 years. Animals were 10.2–13.3 years of age for the PM phase of the
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study, which occurred in July/August 1998. The AM phase was conducted in February 1999 (three animals) and June 1999 (13 animals), a mean of 285 days later. Weights ranged from 9.6 to 15.1 kg (mean ¼ 12:0 kg). Neither age nor weight were associated with personality characteristics (all p > 0:26), except that high confident animals were a mean of 1.4 years older than low confident animals (10.5 vs. 11.9 years; p < 0:05).
2.2. Experimental design and procedure Testing was accomplished in two phases. In the PM phase, blood sampling commenced at 13:00 h, and in the AM phase, sampling commenced at 09:00 h. Daily feeding, which typically occurred at approximately 07:00 and 12:30 h, was delayed until after the final blood sample was collected. In each phase, animals received a single injection of saline, ketamine hydrochloride, or Telazol at weekly intervals. Order of agent within each phase was counterbalanced. On any given day, four to six subjects were tested, only one or two of which received saline. For the PM phase, saline injections and blood sampling for the subjects occurred on nine separate calendar days. For the AM phase, saline injections and blood sampling occurred on 12 separate calendar days. On each test day, the randomly selected subjects had an initial baseline blood sample drawn with blood sampling beginning precisely at 13:00 or 09:00 h. Order of sampling proceeded from the front to the rear of the housing room, and all such ‘‘Time 0’’ samples were collected on a given day within 5.4 min of initial entry into the housing room. From the time the technician approached each animal’s cage, until the time the needle was withdrawn from an animal’s antecubital vein, a mean of 54.8 s (range ¼ 30:0 85:0 s) elapsed. Previous research (Capitanio et al., 1996) demonstrated that blood sampling within these timeframes does not affect cortisol concentrations. Following collection of this sample, animals were injected at 2.5 min intervals with the agent that they were scheduled to receive on that day. Additional blood samples were drawn by armpull at 15, 30, 60, and 120 min post-injection. For each blood sample, 2–3.5 ml of blood were drawn into syringes and immediately transferred to pre-chilled EDTA tubes, and were kept in an ice bath until they could be centrifuged for 20 min at 2200 rpm. Plasma was pipetted into tubes and stored at 80 C until assayed for cortisol concentration by RIA (Diagnostic Products Corp. Los Angeles, CA). The inter-assay CV was 5.8%, and intra-assay CV was 7.9%.
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2.3. Personality assessments
2.4. Data analysis
Details of these procedures can be found in Capitanio (1999). Briefly, 42 adult male monkeys were observed by trained observers (using a focal animal technique) for 4 weeks while living with their natal groups in the half-acre enclosures, and were independently rated by two observers using a battery of 25 adjectives developed by Stevenson-Hinde et al. (1980) for rhesus macaques. Each monkey was rated on each item along a seven point scale (1 ¼ extreme antithesis of the behavior, 7 ¼ extreme manifestation of the behavior). Mean age of the subjects at time of rating was 6.2 years. Twelve of the 25 adjectives met our criteria for adequate inter-rater agreement and reliability (see Capitanio, 1999). Factor analysis of these adjectives revealed four factors (accounting for 68.5% of the total variance) that satisfied the criteria for a scree test (Gorsuch, 1983: p. 166). These factors were rotated (oblique and varimax rotation produced very similar factor patterns), and the four factors were labeled ‘‘Equable’’ (comprising ratings for equable, understanding, and slow), ‘‘Sociable’’ (sociable, playful, curious), ‘‘Confident’’ (confident, aggressive), and ‘‘Excitable’’ (excitable, active, subordinate). (‘‘Effective’’ demonstrated adequate inter-rater agreement and reliability, but was dropped from the final ‘‘Confident’’ scale because it reduced the scale reliability by more than 5%.) Scales were constructed by standardizing the scores for the individual adjectives and then adding the resulting values together using unit weights. Internal consistency reliability for the scales (computed with Cronbach’s alpha) was 0.81, 0.74, 0.74, and 0.74 for Equable, Sociable, Confident, and Excitable, respectively. Of the 42 animals assessed, 36 were selected for a study of the effects of social stability on simian immunodeficiency virus disease progression, with half of the 36 inoculated with SIV (Capitanio et al., 1998). The remaining 18 served as saline-inoculated controls in that study. The 16 subjects in the present study were derived from that latter pool (the two remaining animals had been assigned to other projects). Analysis of the personality data revealed that these 16 animals represented the full range of scores on the four personality dimensions; one-way ANOVAS contrasting personality scores for the 16 current subjects and the 26 animals that had been assessed but were not in the present study revealed nonsignificant group differences: Sociability (p ¼ 0:248), Confidence (p ¼ 0:571), Equability (p ¼ 0:808), Excitability ðp ¼ 0:551Þ.
The goal of the present study was to determine whether Sociability and Excitability were related to cortisol concentrations measured from blood samples drawn over a 2-h period while the animals were in their familiar living cages. Whereas we had explicit hypotheses for these two personality measures, we also conducted exploratory analyses using the remaining two dimensions, Equability and Confidence, in an identical fashion. Four twoway ANOVAs were performed, with each ANOVA including a median split of a different personality dimension (high: above the median; low: below the median) as a between-subjects variable, and time point (0, 15, 30, 60, 120 min post-injection) as a within-subjects variable. Separate ANOVAs were performed for the two phases.
3. Results In the PM phase, both Excitability and Confidence were significantly associated with plasma cortisol concentrations. A main effect for Excitability was found (Fð1; 14Þ ¼ 10:31, p < 0:01). As illustrated in Fig. 1A, high-Excitable animals had 5–8 lg/dl lower cortisol levels than did low-Excitable animals. The ANOVA revealed a significant effect of time as well (Fð4; 56Þ ¼ 6:04, p < 0:001), suggesting that cortisol concentrations declined steadily across the 2-h period. The interaction of Excitability by time was nonsignificant (p ¼ 0:745). For Confidence, a significant interaction of personality by time was evident (Fð4; 56Þ ¼ 6:52, p < 0:001). Tests of simple effects revealed that only high-Confident animals showed the expected circadian decline in cortisol over the 2-h period (Fig. 1B). No effects were found for Sociability (main effect: p ¼ 0:161, interaction with time: p ¼ 0:958; means (SD) for low- and high-Sociable animals, respectively ¼ 18:5 (5.6) and 14.8 (4.1) lg/dl) or for Equability (main effect: p ¼ 0:855; interaction: p ¼ 0:832; means (SD) for low- and high-Equable animals, respectively ¼ 16:1 (4.0) and 17.1 (6.2) lg/dl). During the AM phase, only Confidence was associated with plasma cortisol concentrations, as shown by a significant main effect (Fð1; 14Þ ¼ 5:47, p < 0:05). Fig. 2 demonstrates that animals high in Confidence had plasma cortisol concentrations that were 5–9 lg/dl higher than those found among low-Confidence animals. The interaction of personality and time was nonsignificant (p ¼ 0:568). Analyses for the remaining personality variables were also nonsignificant (Sociability (main effect: p ¼ 0:711; interaction: p ¼ 0:099;
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means (SD) for low- and high-Sociable animals, respectively ¼ 25:5 (4.8) and 26.9 (9.1) lg/dl); Equability (main effect: p ¼ 0:482; interaction: p ¼ 0:906; means (SD) for low- and high-Equable animals, respectively ¼ 27:5 (8.9) and 25.0 (4.9) lg/dl); Excitability (main effect: p ¼ 0:480; interaction: p ¼ 0:787; means (SD) for low- and high-Excitable animals, respectively ¼ 27:4 (4.2) and 24.9 (8.7) lg/dl)).
4. Discussion
Fig. 1. (A) Excitability (based on median split) and mean (SEM) cortisol concentrations for PM phase. (B) Confidence (based on median split) and mean (SEM) cortisol concentrations for PM phase.
Fig. 2. Confidence (based on median split) and mean (SEM) cortisol concentrations for AM phase.
As expected, Excitability was related to plasma cortisol concentrations, though only during the PM phase. Animals higher in Excitability had significantly lower plasma cortisol concentrations during this phase. To the extent that Excitability is related to the human personality dimension ‘‘Neuroticism’’, our results are consistent with those of McCleery and Goodwin (2001), who found that people in the upper quartile on Neuroticism had a lower cortisol response to CRH stimulation (following dexamethasone suppression) than did those who were low on Neuroticism. Their results suggested greater negative feedback sensitivity in high-Neuroticism individuals—that is, high-Neuroticism people would be less likely to mount a strong stress response. Although their cortisol data were obtained following a dex suppression/ CRH stimulation test and were not basal values, greater negative feedback sensitivity could be manifested as lower basal levels. In fact, two studies, one in our laboratory (Capitanio et al., 1998) and one involving humans (Yehuda et al., 1995) have found lower basal cortisol concentrations in individuals that demonstrated other evidence of enhanced negative feedback sensitivity. Thus, our data suggest that Excitability may be associated, even in normal populations, with differences in regulation of the HPA axis. It is unclear why Excitability was related to cortisol concentrations only during the PM phase and not during the AM phase. Had testing occurred on a single day, AM vs. PM differences might have reflected the occurrence of an unusual event, unknown to us, that might have occurred just prior to blood sampling. In our study, however, PM blood sampling occurred on nine separate days, reducing the chance that this result is an artifact. It is possible that this result reflects diurnal differences in normal HPA axis functioning. Negative feedback is more effective at the trough of the circadian cycle (Bradbury et al., 1994), so if Excitability is associated with negative feedback, group differences should be most apparent when negative feedback is having the greatest impact, such as when re-establishing baseline concentrations
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following an acute response, or when values are approaching the low-point in the diurnal cycle which, in our study, occurred during the PM phase. The results were also consistent with our second expectation that Sociability was unlikely to be related to cortisol concentrations in this nonsocial situation. We recognize, of course, that one cannot prove the null hypothesis statistically. In fact, there were slight differences in cortisol between our low- and high-Sociable animals, especially in the PM phase, where low-Sociable animals had a 3.7 lg/dl (equivalent to 25%) greater concentration compared to high-Sociable animals. To assess whether Sociability was truly associated with mean PM cortisol concentrations, we conducted a multiple regression analysis using the four dichotomized personality variables as independent variables, and found that the value of correlation coefficients between Sociability and cortisol changed from the bivariate r ¼ 0:368 to a partial r ¼ 0:027. Excitability remained a strong predictor of PM cortisol. Thus, the (nonsignificant) group difference of 3.7 lg/dl for high- vs. lowSociability in the PM phase appears to reflect shared variance among our dichotomized personality variables Sociability and Excitability, rather than a real effect of Sociability. We acknowledge that our sample size is low, however, and recognize that replication would be valuable to confirm this effect. The most surprising result from our analysis was that Confidence was related to cortisol concentrations at both time points, as a main effect during the AM phase, and as an interaction effect during the PM phase. We are unclear how our dimension of Confidence might relate to human personality dimensions. Animals high in Confidence display behaviors that reflect higher social rank when meeting new animals, such as aggression and threats, and they tend to receive more behaviors consistent with that picture as well, such as fear grimaces and sex presents. They are not, however, hyper-aggressive in such situations. Nor is Confidence a personality dimension that only we have found; others studying rhesus monkeys as well as other nonhuman primate species have found Confidence/dominance factors (see Gosling and John, 1999). This dimension may be peculiar to species in which social rank hierarchies are strong organizing influences on their societies. While our results seem to contradict the common notion that subordinates have higher cortisol concentrations (though see Abbott et al., 2003; Bentson, 1998), we note that dominance is a characteristic of a relationship, not an individual (Capitanio, 1991), and that it is unclear how Con-
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fidence and dominance inter-relate. In fact, the simple picture of cortisol and dominance is now recognized as more complex, with factors such as personality and temperament influencing the relationship (Sapolsky and Ray, 1989; Virgin and Sapolsky, 1997). Inspection of Figs. 1B and 2 together suggests an intriguing relationship between Confidence and cortisol. Although the PM and AM phases were separated by about 9 months, the data suggest that high-Confidence animals displayed the expected diurnal rhythm, but low-Confidence animals do not. Among high-Confidence animals, cortisol concentrations at the 120-min time point (which would correspond to 11:00 h) were 28.0 lg/dl, whereas concentrations at the 0-min time point for the PM phase (which would correspond to 13:00 h) were 24.3 lg/dl, and then cortisol declined to12.3 lg/dl by 15:00 h. In contrast, the corresponding cortisol values for the low-Confidence animals are 21.7 (11:00 h), 15.9 (13:00 h), and 15.7 (15:00 h) lg/dl. Thus, low-Confidence animals appear to show an alteration in the normal diurnal cortisol rhythm, which was most evident in the PM phase. Another potential explanation for the flat response pattern of the low-Confidence monkeys is that perhaps the downward trend of the circadian rhythm was offset by a mild phlebotomyinduced stress response. That is, perhaps for low-Confidence animals (or for other animals), the values presented here are not in fact basal values. While we recognize that we cannot reject this possibility completely, we do consider it unlikely for several reasons. First, the values presented in this paper are consistent with values presented as ‘‘basal values’’ in other published work in our (Capitanio et al., 1996) and others’ labs (Reinhardt et al., 1990). Second, comparable values have been obtained in our own lab (unpublished), in which blood samples were drawn from freely moving animals instrumented with a backpack device (Bentson et al., 1999) that collected blood unobtrusively, at the same times of day, from an indwelling catheter, thus eliminating the influence of the phlebotomy, per se. Third, using an identical blood sampling procedure as described herein, we demonstrated that animals that are not trained to cooperate with venipuncture (and so are likely to be stressed by the process of repeated plebotomy), show an elevation of approximately 15 lg/dl over the 2-h session, unlike the animals in the present study whose levels declined, or, in the case of the low-Confidence animals, remained essentially flat (Bentson et al., 2003). Fourth, there were no differences
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between low- and high-Confidence animals in the present study in either the amount of time it took technicians to draw the blood samples for each monkey, or the amount of total disturbance time that the technicians were in the room before the samples were obtained; thus this difference does not seem to reflect an artifact of the blood sampling procedures. Finally, although low-Confidence animals were 1.4 years younger than high-Confidence animals, we are unaware of any age-related differences between 10 and 12 year old adult male rhesus monkeys in responsiveness to potential stressors; moreover, correlations between age and cortisol concentrations at each time point in the present study were all nonsignificant (all p > 0:25) suggesting that our results were not an aspect of a more general agerelated difference. Thus, we feel confident that our data reflect basal values, although we recognize that the present work requires extension to distinguish firmly between the two explanations for the low- vs. high-Confidence animals. Consequently, we offer as provisional our interpretation that the results for low-Confidence animals represent a flattened diurnal rhythm, and not a mild stress-induced response. While we are aware of no human research relating personality to variations in cortisol rhythmicity, one study that employed a healthy community sample (n ¼ 120) demonstrated that 51% had the normal ‘‘negative’’ cycle on two consecutive days, 31% had inconsistent cycles from one day to the next, and 17% of subjects had no discernable circadian rhythm (Smyth et al., 1997; see also Stone et al., 2001 for further, similar, results). Cycle type was not related to any demographic or psychological variable (including experience of stressors) measured. Unfortunately, subjects’ personality characteristics were not assessed in these studies. Health consequences have been related to aspects of cortisol rhythmicity, however, with flatter rhythms associated with earlier mortality and suppressed natural killer cell function in patients with metastatic breast cancer (Sephton et al., 2000), but also with fewer upper respiratory infection symptoms (Smyth et al., 1997; Edwards et al., 2003). Interestingly, Edwards et al. (2003) demonstrated that individuals with a ‘‘flat’’ cortisol profile spent significantly fewer hours in busy places in close proximity to others (e.g., restaurants, pubs, lectures, meetings) compared to individuals with a normal profile. This suggests that humans with a flat profile might be less socially assertive, as are our low-Confidence monkeys, who also show a flat profile. Three other studies with nonhuman primates have examined plasma cortisol concentrations and
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personality characteristics using the multidimensional rating methodology. In an earlier study (Capitanio et al., 1999), conducted with a separate cohort of animals, we found positive correlations between Confidence and Excitability and a negative correlation with Sociability for basal concentrations of cortisol taken at 15:00 h. The animals in this study, however, were experiencing on a daily basis unfamiliar and presumably stressful social manipulations that, in fact, altered HPA regulation (Capitanio et al., 1998). A study by Laudenslager et al. (1999) of juvenile rhesus monkeys on an island colony found no relationships between cortisol concentrations and their three personality factors of Insecurity, Irritability, and Sociability. Although there were some methodological differences with derivation of the personality factors, morning blood samples on these animals were collected after netting/hand capture followed by ketamine immobilization. In fact, the authors acknowledge that their cortisol concentrations represent stressed values, which is borne out by examination of their Fig. 2. Finally, Byrne and Suomi (2002) correlated cortisol concentrations with individually rated traits (i.e., the component traits that were factor-analyzed in the present study and by Laudenslager et al. (1999)). Several relationships were found with stress concentrations, but only ‘‘Strong’’ and ‘‘Submissive’’ showed correlations (positive and negative, respectively) with basal levels. It was not clear when the samples were taken in this study, but the negative relationship between basal cortisol and ‘‘Submissive’’ mirrors our result for Excitability (which includes an identically defined trait ‘‘Subordinate’’) and afternoon basal samples. In conclusion, our data suggest that cortisol concentrations in our adult male rhesus monkeys are related to personality characteristics in both expected and unexpected ways. While we recognize that our results require replication with larger samples, these data do show some intriguing consistencies with the human data. In general, however, there has been relatively little study of neuroendocrine relationships and personality factors in normal populations of either human or nonhuman primates. Even in welldesigned studies, individual variation exists in measures such as cortisol concentration; our data and the data from the few human studies described above indicate that such variation can be explained to some extent by consideration of personality characteristics. The data also suggest that greater attention should be paid to the dynamic characteristics of the HPA axis, in particular to diurnal rhythmicity. In any system, there
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are multiple characteristics such as set-points, peak values, quality and quantity of response to challenge, rates of decline, and so forth that describe the functioning of that system. It remains to be determined which factors (e.g., personality, experiences, genetics) explain individual variation in these parameters, and how such relationships affect meaningful organismic outcomes such as indices of mental or physical health. Parallel studies in both human and nonhuman animals can be a valuable strategy to address these questions.
Acknowledgements The authors thank C. Brennan for assistance in figure preparation, and L. Martson, G. Vicino, and the veterinary and animal care staff of CNPRC for technical assistance with data collection and care of the animals. Supported by MH49033 and RR00169. The California National Primate Research Center is accredited by the Association for the Assessment and Accreditation of Laboratory Animal Care International. All procedures were carried out in accordance with guidelines of the Public Health Service, USA.
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capuchin (Cebus apella) juveniles from birth to six years of age. Psychoneuroendocrinology 27, 139–154. Capitanio, J.P., 1991. Levels of integration and the ‘inheritance of dominance’. Animal Behaviour 42, 495–496. Capitanio, J.P., 1999. Personality dimensions in adult male rhesus macaques: prediction of behaviors across time and situation. American Journal of Primatology 47 (4), 299–320. Capitanio, J.P., Mendoza, S.P., McChesney, M., 1996. Influences of blood sampling procedures on basal hypothalamicpituitary-adrenal hormone levels and leukocyte values in rhesus macaques (Macaca mulatta). Journal of Medical Primatology 25, 26–33. Capitanio, J.P., Mendoza, S.P., Lerche, N.W., Mason, W.A., 1998. Social stress results in altered glucocorticoid regulation and shorter survival in simian acquired immune deficiency syndrome. Proceedings of the National Academy of Sciences 95 (8), 4714–4719. Capitanio, J.P., Mendoza, S.P., Baroncelli, S., 1999. The relationship of personality dimensions in adult male rhesus macaques to progression of simian immunodeficiency virus disease. Brain, Behavior and Immunity 13, 138–154. Cloninger, C.R., 1986. A unified biosocial theory of personality and its role in the development of anxiety states. Psychiatric Developments 3, 167–226. Edwards, S., Hucklebridge, F., Clow, A., Evans, P., 2003. Components of the diurnal cortisol cycle in relation to upper respiratory symptoms and perceived stress. Psychosomatic Medicine 65, 320–327. Gorsuch, R.L., 1983. Factor Analysis, second ed. Erlbaum, Hillsdale, NJ. Gosling, S.D., John, O.P., 1999. Personality dimensions in nonhuman animals: a cross-species review. Current Directions in Psychological Science 8 (3), 69–75. Hart, D., Atkins, R., Fegley, S.G., 2003. Personality and development in childhood: a person-centered approach. Monographs of the Society for Research in Child Development 68, 1–109. Heim, C., Newport, D.J., Heit, S., Graham, Y.P., Wilcox, M., Bonsall, R., Miller, A.H., Nemeroff, C.B., 2000. Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood. JAMA 284 (5), 592–597. Kagan, J., Reznick, J.S., Snidman, N., 1988. Biological bases of childhood shyness. Science 240, 167–171. Laudenslager, M.L., Rasmussen, K.L., Berman, C.M., Lilly, A.A., Shelton, S.E., Kalin, N.H., Suomi, S.J., 1999. A preliminary description of responses of free-ranging rhesus monkeys to brief capture experiences: behavior, endocrine, immune, and health relationships. Brain, Behavior, and Immunity 13, 124–137. Levine, S., 2000. Influence of psychological variables on the activity of the hypothalamic-pituitary-adrenal axis. European Journal of Pharmacology 405, 149–160. Maninger, N., Capitanio, J.P., Mendoza, S.P., Mason, W.A., 2003. Personality influences tetanus-specific antibody response in adult male rhesus macaques after removal from natal group and housing relocation. American Journal of Primatology 61 (2), 73–83. McCleery, J.M., Goodwin, G.M., 2001. High and low neuroticism predict different cortisol responses to the combined dexamethasone-CRH test. Biological Psychiatry 49, 410–415. Miller, G.E., Cohen, S., Rabin, B.S., Skoner, D.P., Doyle, W.J., 1999. Personality and tonic cardiovascular, neuroendocrine, and immune parameters. Brain, Behavior, and Immunity 13, 109–123. Reinhardt, V., Cowley, D., Scheffler, J., Vertein, R., Wegner, F., 1990. Cortisol response of female rhesus monkeys to
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venipuncture in homecage versus venipuncture in restraint apparatus. Journal of Medical Primatology 19, 601–606. Rosenblitt, J.C., Soler, H., Johnson, S.E., Quadagno, D.M., 2001. Sensation seeking and hormones in men and women: exploring the link. Hormones and Behavior 40, 396–402. Roy, A., 2002. Childhood trauma and neuroticism as an adult: possible implication for the development of the common psychiatric disorders and suicidal behavior. Psychological Medicine 32, 1471–1474. Sapolsky, R.M., Ray, J.C., 1989. Styles of dominance and their endocrine correlates among wild olive baboons (Papio anubis). American Journal of Primatology 18, 1–13. Sephton, S.E., Sapolsky, R.M., Kraemer, H.C., Spiegel, D., 2000. Diurnal cortisol rhythm as a predictor of breast cancer survival. Journal of the National Cancer Institute 92, 994–1000. Smyth, J.M., Ockenfels, M.C., Gorin, A.A., Catley, D., Porter, L.S., Kirschbaum, C., Hellhammer, D.H., Stone, A.A., 1997. Individual differences in the diurnal cycle of cortisol. Psychoneuroendocrinology 22 (2), 89–105.
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Stevenson-Hinde, J., Stillwell-Barnes, R., Zunz, M., 1980. Subjective assessment of rhesus monkeys over four successive years. Primates 21, 66–82. Stone, A., Schwartz, J.E., Smyth, J., Kirschbaum, C., Cohen, S., Hellhammer, D., Grossman, S., 2001. Individual differences in the diurnal cycle of salivary free cortisol: a replication of flattened cycles for some invidivuals. Psychoneuroendocrinology 26, 295–306. Virgin, Jr., C.E., Sapolsky, R.M., 1997. Styles of male social behavior and their endocrine correlates among low-ranking baboons. American Journal of Primatology 42, 25–39. Winter, D.G., John, O.P., Stewart, A.J., Klohnen, E.C., Duncan, L.E., 1998. Traits and motives: toward an integration of two traditions in personality research. Psychological Review 105, 230–250. Yehuda, R., Giller, Jr., E.L., Levengood, R.A., Southwick, S.M., Siever, L.J., 1995. Hypothalamic-pituitary-adrenal functioning in post-traumatic stress disorder: expanding the concept of the stress response spectrum. In: Friedman, M.J., Charney, D.S., Deutch, A.Y. (Eds.), Neurobiological and Clinical Consequences of Stress: From Normal Adaptation to PTSD. Lippincott-Raven Publishers, Philadelphia, pp. 351–365.
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Personality characteristics and basal cortisol concentrations in adult male rhesus macaques (Macaca mulatta) John P. Capitanioa,b,*, Sally P. Mendozaa,b, Kathleen L. Bentsonb,c a
Department of Psychology, University of California, Davis, CA, USA California National Primate Research Center, University of California, One Shields Avenue, Davis, CA 95616, USA c Washington National Primate Research Center, University of Washington, USA b
Received 29 October 2003; received in revised form 26 March 2004; accepted 2 April 2004
KEYWORDS Personality; Hormones; Cortisol; Circadian rhythm; Monkeys
Summary Although data show that psychosocial factors can regulate physiological processes, few data have been collected on normative populations. Studies in humans have suggested that personality characteristics might be related to regulation of the hypothalamic–pituitary–adrenal (HPA) axis. We explored the relationship between personality characteristics and plasma cortisol concentrations in adult male rhesus macaques. Two sets of blood samples were obtained from monkeys using a procedure with which they were very familiar; thus, cortisol concentrations reflected basal values. Analyses indicated high-excitable animals had lower basal cortisol concentrations during the afternoon period, and that low-confidence was associated with lower cortisol in the morning period, and lack of a circadian decline in the afternoon period. Sociability and equability were unrelated to cortisol levels. Our data confirm and extend some results found in human studies, and suggest that even in normal populations, personality characteristics are related to measures of HPA function. We propose that comparative studies of personality in nonhuman primates that parallel studies in humans can increase our understanding of mechanisms whereby personality may relate to mental and physical health outcomes. # 2004 Elsevier Ltd. All rights reserved.
1. Introduction Personality is a major individual differences construct in psychology. Early theorizing about personality (e.g., Allport, 1937) identified many of the themes that have been elaborated upon in the * Corresponding author. Tel.: +1-530-752-4002; fax: +1-530752-2880. E-mail address: [email protected] (J.P. Capitanio).
last half century—the fact that personality comprises multiple dimensions (whether of traits or motives: Winter et al., 1998); that personality has a neural basis (e.g., Cloninger, 1986); and that personality is associated with physiological measures and health outcomes (e.g., Adler, 1994; Miller et al., 1999). While personality correlates of a number of physiological systems have been explored, particular interest has focused on hormones of the hypothalamic–pituitary–adrenal
0306-4530/$ - see front matter # 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.psyneuen.2004.04.001
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(HPA) axis, which is responsive to situations that engender psychological stress. Experimental research in animals, for example, has demonstrated that particular rearing conditions, which affect personality-related processes such as emotionality and responsiveness, also profoundly affect characteristics of the HPA axis (e.g., Levine, 2000). Similarly, research with humans has demonstrated that early adverse experiences such as sexual and emotional abuse also affect personality (e.g., Roy, 2002) and HPA function and regulation (e.g., Heim et al., 2000). While there is strong evidence that the HPA system is responsive to experimentally induced manipulations such as nursery- (as compared to mother-) rearing in monkeys, or to severe traumatic events such as the early experience of child abuse in humans, far less is known about how naturally occurring variation in characteristics of normal individuals might relate to HPA functioning. Studies of ‘‘normal’’ populations provide complementary information on the generality of a result found with clinical or extreme samples, allowing one to infer, for example, whether relationships are linear or curvilinear. Such studies also provide the basis for taking a ‘‘person-centered’’ approach to personality, where the focus is on identifying personality ‘‘types’’ that comprise relatively distinct subgroups of individuals that exhibit a clustering of traits (e.g., Hart et al., 2003). A good example of the typological approach is the work of Kagan and colleagues who have focused on early infant temperament. Children described as ‘‘inhibited’’ as infants—evidenced by long latencies to play, speak, and interact with unfamiliar individuals—have higher morning cortisol concentrations compared to uninhibited children at 5.5 years of age (Kagan et al., 1988), a result consistent with other data suggesting that inhibited children show greater physiological responsiveness. Only a few studies of normal populations of adult humans have focused on relationships between personality dimensions and HPA measures. Miller et al. (1999) reported small but significant correlations between morning plasma cortisol concentrations and the personality dimensions Extraversion and Neuroticism (r ¼ 0:17 and 0.18, n ¼ 276, respectively). No relationship was found between cortisol and agreeableness. In contrast, McCleery and Goodwin (2001) reported that young adults in the upper quartile for Neuroticism had a smaller increase in cortisol levels following a combined dexamethasone suppression/CRH stimulation test, compared to those in the lower quartile on Neuroticism. This result suggested to the authors that individuals high in Neuroticism
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may have enhanced glucocorticoid negative feedback sensitivity. Finally, basal salivary cortisol has been found to be negatively associated with Sensation Seeking (a personality dimension that reflects impulsivity) in one study (Rosenblitt et al., 2001). As part of a larger project examining the role that social factors play in endocrine and immune functioning in adult male rhesus macaques (e.g., Capitanio et al., 1998), we have had a secondary focus on how personality characteristics influence behavior and physiology. We have identified four personality dimensions (Capitanio, 1999)—Sociability, Confidence, Equability, and Excitability— though our principal interest has been with Sociability, which represents a tendency to affiliate (and which has been suggested as being similar to the human personality dimension Extraversion: Gosling and John, 1999). Our data have indicated that individual differences in Sociability predict behavioral and physiological functioning in situations that have social import to animals (Capitanio et al., 1999; Maninger et al., 2003). Our goal in the present report was twofold— first, to determine whether, in a situation that is decidedly nonsocial (repeated phlebotomy of animals while they are in their individual housing cages), Sociability would predict cortisol concentrations; and second, whether other aspects of primate personality, specifically Excitability, would affect cortisol levels. Despite the modest result reported in humans by Miller et al. (1999), we expected that Sociability would not be related to cortisol concentrations, inasmuch as this dimension is unlikely to contribute to the animals’ functioning in nonsocial situations. In contrast, Excitability appears to be a dimension reflecting overall emotional reactivity, and in fact has been likened to the human dimension of Neuroticism (Gosling and John, 1999). For example, when individually housed adult male rhesus monkeys are presented with a threatening human, scores on the dimension Excitability alone predict their behavioral response—more Excitable animals spend more time in the front of the cage nearest the human threatening him. Scores on the other dimensions did not predict behavioral responses in this situation (Capitanio, 1999). Excitability does contribute to responses in social situations as well, and seems to reflect generalized behavioral responsiveness, which is often manifested as combinations of aggressive, affiliative, and fearful behaviors, sometimes displayed in rapid succession. An earlier study, with a separate set of animals, indicated that Excitability was correlated positively with cortisol concentrations measured
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during a study involving social exposures (Capitanio et al., 1999). Thus, we predicted that highand low-Excitable animals might differ in cortisol concentrations in a nonsocial situation as well. The conflicting results for Neuroticism reported above for the human studies, however, suggested a two-tailed approach to this hypothesis. We did not have specific predictions for our other two personality dimensions, Equability (reflecting, perhaps, agreeableness) and Confidence (which correlates with aggressiveness in rhesus monkeys, and may be a species-specific composite dimension reflecting low agreeableness and Extraversion). Blood samples were taken from 16 adult male rhesus monkeys while they were in their familiar, individual living cages. The animals were subjects in a study designed to assess whether the anesthetic agents ketamine and Telazol affected cortisol concentrations during the 2 h following administration of the agent. These data have been published (Bentson et al., 2003). A third condition, saline injection, was also included as a control condition. In the present report, we examine how personality factors relate to cortisol concentrations during repeated blood sampling (a procedure with which the animals had considerable experience) during the 2 h following saline administration.
2. Methods 2.1. Subjects Subjects were 16 adult male rhesus monkeys (Macaca mulatta). All were born in half-acre corrals at the California National Primate Research Center, each comprising 60–100 animals with an age/sex structure approximating that found in feral troops. The subjects had lived in individual indoor cages (standard stainless steel cages equipped with squeeze-back mechanisms) for 5 years prior to the start of this study. Animals had participated in a series of studies examining behavioral and physiological responses in various social situations, but had not been on-project for more than a year prior to the start of the current study. Animals were, however, paired with a familiar partner in another room for 1–2 h periods several days per week. Animals were not socialized on the day of blood sampling. Each animal had been trained to cooperate during venipuncture, and each animal was very familiar with the procedure, having experienced sample collection via armpull at approximately monthly intervals during the previous 5 years. Animals were 10.2–13.3 years of age for the PM phase of the
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study, which occurred in July/August 1998. The AM phase was conducted in February 1999 (three animals) and June 1999 (13 animals), a mean of 285 days later. Weights ranged from 9.6 to 15.1 kg (mean ¼ 12:0 kg). Neither age nor weight were associated with personality characteristics (all p > 0:26), except that high confident animals were a mean of 1.4 years older than low confident animals (10.5 vs. 11.9 years; p < 0:05).
2.2. Experimental design and procedure Testing was accomplished in two phases. In the PM phase, blood sampling commenced at 13:00 h, and in the AM phase, sampling commenced at 09:00 h. Daily feeding, which typically occurred at approximately 07:00 and 12:30 h, was delayed until after the final blood sample was collected. In each phase, animals received a single injection of saline, ketamine hydrochloride, or Telazol at weekly intervals. Order of agent within each phase was counterbalanced. On any given day, four to six subjects were tested, only one or two of which received saline. For the PM phase, saline injections and blood sampling for the subjects occurred on nine separate calendar days. For the AM phase, saline injections and blood sampling occurred on 12 separate calendar days. On each test day, the randomly selected subjects had an initial baseline blood sample drawn with blood sampling beginning precisely at 13:00 or 09:00 h. Order of sampling proceeded from the front to the rear of the housing room, and all such ‘‘Time 0’’ samples were collected on a given day within 5.4 min of initial entry into the housing room. From the time the technician approached each animal’s cage, until the time the needle was withdrawn from an animal’s antecubital vein, a mean of 54.8 s (range ¼ 30:0 85:0 s) elapsed. Previous research (Capitanio et al., 1996) demonstrated that blood sampling within these timeframes does not affect cortisol concentrations. Following collection of this sample, animals were injected at 2.5 min intervals with the agent that they were scheduled to receive on that day. Additional blood samples were drawn by armpull at 15, 30, 60, and 120 min post-injection. For each blood sample, 2–3.5 ml of blood were drawn into syringes and immediately transferred to pre-chilled EDTA tubes, and were kept in an ice bath until they could be centrifuged for 20 min at 2200 rpm. Plasma was pipetted into tubes and stored at 80 C until assayed for cortisol concentration by RIA (Diagnostic Products Corp. Los Angeles, CA). The inter-assay CV was 5.8%, and intra-assay CV was 7.9%.
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2.3. Personality assessments
2.4. Data analysis
Details of these procedures can be found in Capitanio (1999). Briefly, 42 adult male monkeys were observed by trained observers (using a focal animal technique) for 4 weeks while living with their natal groups in the half-acre enclosures, and were independently rated by two observers using a battery of 25 adjectives developed by Stevenson-Hinde et al. (1980) for rhesus macaques. Each monkey was rated on each item along a seven point scale (1 ¼ extreme antithesis of the behavior, 7 ¼ extreme manifestation of the behavior). Mean age of the subjects at time of rating was 6.2 years. Twelve of the 25 adjectives met our criteria for adequate inter-rater agreement and reliability (see Capitanio, 1999). Factor analysis of these adjectives revealed four factors (accounting for 68.5% of the total variance) that satisfied the criteria for a scree test (Gorsuch, 1983: p. 166). These factors were rotated (oblique and varimax rotation produced very similar factor patterns), and the four factors were labeled ‘‘Equable’’ (comprising ratings for equable, understanding, and slow), ‘‘Sociable’’ (sociable, playful, curious), ‘‘Confident’’ (confident, aggressive), and ‘‘Excitable’’ (excitable, active, subordinate). (‘‘Effective’’ demonstrated adequate inter-rater agreement and reliability, but was dropped from the final ‘‘Confident’’ scale because it reduced the scale reliability by more than 5%.) Scales were constructed by standardizing the scores for the individual adjectives and then adding the resulting values together using unit weights. Internal consistency reliability for the scales (computed with Cronbach’s alpha) was 0.81, 0.74, 0.74, and 0.74 for Equable, Sociable, Confident, and Excitable, respectively. Of the 42 animals assessed, 36 were selected for a study of the effects of social stability on simian immunodeficiency virus disease progression, with half of the 36 inoculated with SIV (Capitanio et al., 1998). The remaining 18 served as saline-inoculated controls in that study. The 16 subjects in the present study were derived from that latter pool (the two remaining animals had been assigned to other projects). Analysis of the personality data revealed that these 16 animals represented the full range of scores on the four personality dimensions; one-way ANOVAS contrasting personality scores for the 16 current subjects and the 26 animals that had been assessed but were not in the present study revealed nonsignificant group differences: Sociability (p ¼ 0:248), Confidence (p ¼ 0:571), Equability (p ¼ 0:808), Excitability ðp ¼ 0:551Þ.
The goal of the present study was to determine whether Sociability and Excitability were related to cortisol concentrations measured from blood samples drawn over a 2-h period while the animals were in their familiar living cages. Whereas we had explicit hypotheses for these two personality measures, we also conducted exploratory analyses using the remaining two dimensions, Equability and Confidence, in an identical fashion. Four twoway ANOVAs were performed, with each ANOVA including a median split of a different personality dimension (high: above the median; low: below the median) as a between-subjects variable, and time point (0, 15, 30, 60, 120 min post-injection) as a within-subjects variable. Separate ANOVAs were performed for the two phases.
3. Results In the PM phase, both Excitability and Confidence were significantly associated with plasma cortisol concentrations. A main effect for Excitability was found (Fð1; 14Þ ¼ 10:31, p < 0:01). As illustrated in Fig. 1A, high-Excitable animals had 5–8 lg/dl lower cortisol levels than did low-Excitable animals. The ANOVA revealed a significant effect of time as well (Fð4; 56Þ ¼ 6:04, p < 0:001), suggesting that cortisol concentrations declined steadily across the 2-h period. The interaction of Excitability by time was nonsignificant (p ¼ 0:745). For Confidence, a significant interaction of personality by time was evident (Fð4; 56Þ ¼ 6:52, p < 0:001). Tests of simple effects revealed that only high-Confident animals showed the expected circadian decline in cortisol over the 2-h period (Fig. 1B). No effects were found for Sociability (main effect: p ¼ 0:161, interaction with time: p ¼ 0:958; means (SD) for low- and high-Sociable animals, respectively ¼ 18:5 (5.6) and 14.8 (4.1) lg/dl) or for Equability (main effect: p ¼ 0:855; interaction: p ¼ 0:832; means (SD) for low- and high-Equable animals, respectively ¼ 16:1 (4.0) and 17.1 (6.2) lg/dl). During the AM phase, only Confidence was associated with plasma cortisol concentrations, as shown by a significant main effect (Fð1; 14Þ ¼ 5:47, p < 0:05). Fig. 2 demonstrates that animals high in Confidence had plasma cortisol concentrations that were 5–9 lg/dl higher than those found among low-Confidence animals. The interaction of personality and time was nonsignificant (p ¼ 0:568). Analyses for the remaining personality variables were also nonsignificant (Sociability (main effect: p ¼ 0:711; interaction: p ¼ 0:099;
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means (SD) for low- and high-Sociable animals, respectively ¼ 25:5 (4.8) and 26.9 (9.1) lg/dl); Equability (main effect: p ¼ 0:482; interaction: p ¼ 0:906; means (SD) for low- and high-Equable animals, respectively ¼ 27:5 (8.9) and 25.0 (4.9) lg/dl); Excitability (main effect: p ¼ 0:480; interaction: p ¼ 0:787; means (SD) for low- and high-Excitable animals, respectively ¼ 27:4 (4.2) and 24.9 (8.7) lg/dl)).
4. Discussion
Fig. 1. (A) Excitability (based on median split) and mean (SEM) cortisol concentrations for PM phase. (B) Confidence (based on median split) and mean (SEM) cortisol concentrations for PM phase.
Fig. 2. Confidence (based on median split) and mean (SEM) cortisol concentrations for AM phase.
As expected, Excitability was related to plasma cortisol concentrations, though only during the PM phase. Animals higher in Excitability had significantly lower plasma cortisol concentrations during this phase. To the extent that Excitability is related to the human personality dimension ‘‘Neuroticism’’, our results are consistent with those of McCleery and Goodwin (2001), who found that people in the upper quartile on Neuroticism had a lower cortisol response to CRH stimulation (following dexamethasone suppression) than did those who were low on Neuroticism. Their results suggested greater negative feedback sensitivity in high-Neuroticism individuals—that is, high-Neuroticism people would be less likely to mount a strong stress response. Although their cortisol data were obtained following a dex suppression/ CRH stimulation test and were not basal values, greater negative feedback sensitivity could be manifested as lower basal levels. In fact, two studies, one in our laboratory (Capitanio et al., 1998) and one involving humans (Yehuda et al., 1995) have found lower basal cortisol concentrations in individuals that demonstrated other evidence of enhanced negative feedback sensitivity. Thus, our data suggest that Excitability may be associated, even in normal populations, with differences in regulation of the HPA axis. It is unclear why Excitability was related to cortisol concentrations only during the PM phase and not during the AM phase. Had testing occurred on a single day, AM vs. PM differences might have reflected the occurrence of an unusual event, unknown to us, that might have occurred just prior to blood sampling. In our study, however, PM blood sampling occurred on nine separate days, reducing the chance that this result is an artifact. It is possible that this result reflects diurnal differences in normal HPA axis functioning. Negative feedback is more effective at the trough of the circadian cycle (Bradbury et al., 1994), so if Excitability is associated with negative feedback, group differences should be most apparent when negative feedback is having the greatest impact, such as when re-establishing baseline concentrations
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following an acute response, or when values are approaching the low-point in the diurnal cycle which, in our study, occurred during the PM phase. The results were also consistent with our second expectation that Sociability was unlikely to be related to cortisol concentrations in this nonsocial situation. We recognize, of course, that one cannot prove the null hypothesis statistically. In fact, there were slight differences in cortisol between our low- and high-Sociable animals, especially in the PM phase, where low-Sociable animals had a 3.7 lg/dl (equivalent to 25%) greater concentration compared to high-Sociable animals. To assess whether Sociability was truly associated with mean PM cortisol concentrations, we conducted a multiple regression analysis using the four dichotomized personality variables as independent variables, and found that the value of correlation coefficients between Sociability and cortisol changed from the bivariate r ¼ 0:368 to a partial r ¼ 0:027. Excitability remained a strong predictor of PM cortisol. Thus, the (nonsignificant) group difference of 3.7 lg/dl for high- vs. lowSociability in the PM phase appears to reflect shared variance among our dichotomized personality variables Sociability and Excitability, rather than a real effect of Sociability. We acknowledge that our sample size is low, however, and recognize that replication would be valuable to confirm this effect. The most surprising result from our analysis was that Confidence was related to cortisol concentrations at both time points, as a main effect during the AM phase, and as an interaction effect during the PM phase. We are unclear how our dimension of Confidence might relate to human personality dimensions. Animals high in Confidence display behaviors that reflect higher social rank when meeting new animals, such as aggression and threats, and they tend to receive more behaviors consistent with that picture as well, such as fear grimaces and sex presents. They are not, however, hyper-aggressive in such situations. Nor is Confidence a personality dimension that only we have found; others studying rhesus monkeys as well as other nonhuman primate species have found Confidence/dominance factors (see Gosling and John, 1999). This dimension may be peculiar to species in which social rank hierarchies are strong organizing influences on their societies. While our results seem to contradict the common notion that subordinates have higher cortisol concentrations (though see Abbott et al., 2003; Bentson, 1998), we note that dominance is a characteristic of a relationship, not an individual (Capitanio, 1991), and that it is unclear how Con-
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fidence and dominance inter-relate. In fact, the simple picture of cortisol and dominance is now recognized as more complex, with factors such as personality and temperament influencing the relationship (Sapolsky and Ray, 1989; Virgin and Sapolsky, 1997). Inspection of Figs. 1B and 2 together suggests an intriguing relationship between Confidence and cortisol. Although the PM and AM phases were separated by about 9 months, the data suggest that high-Confidence animals displayed the expected diurnal rhythm, but low-Confidence animals do not. Among high-Confidence animals, cortisol concentrations at the 120-min time point (which would correspond to 11:00 h) were 28.0 lg/dl, whereas concentrations at the 0-min time point for the PM phase (which would correspond to 13:00 h) were 24.3 lg/dl, and then cortisol declined to12.3 lg/dl by 15:00 h. In contrast, the corresponding cortisol values for the low-Confidence animals are 21.7 (11:00 h), 15.9 (13:00 h), and 15.7 (15:00 h) lg/dl. Thus, low-Confidence animals appear to show an alteration in the normal diurnal cortisol rhythm, which was most evident in the PM phase. Another potential explanation for the flat response pattern of the low-Confidence monkeys is that perhaps the downward trend of the circadian rhythm was offset by a mild phlebotomyinduced stress response. That is, perhaps for low-Confidence animals (or for other animals), the values presented here are not in fact basal values. While we recognize that we cannot reject this possibility completely, we do consider it unlikely for several reasons. First, the values presented in this paper are consistent with values presented as ‘‘basal values’’ in other published work in our (Capitanio et al., 1996) and others’ labs (Reinhardt et al., 1990). Second, comparable values have been obtained in our own lab (unpublished), in which blood samples were drawn from freely moving animals instrumented with a backpack device (Bentson et al., 1999) that collected blood unobtrusively, at the same times of day, from an indwelling catheter, thus eliminating the influence of the phlebotomy, per se. Third, using an identical blood sampling procedure as described herein, we demonstrated that animals that are not trained to cooperate with venipuncture (and so are likely to be stressed by the process of repeated plebotomy), show an elevation of approximately 15 lg/dl over the 2-h session, unlike the animals in the present study whose levels declined, or, in the case of the low-Confidence animals, remained essentially flat (Bentson et al., 2003). Fourth, there were no differences
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between low- and high-Confidence animals in the present study in either the amount of time it took technicians to draw the blood samples for each monkey, or the amount of total disturbance time that the technicians were in the room before the samples were obtained; thus this difference does not seem to reflect an artifact of the blood sampling procedures. Finally, although low-Confidence animals were 1.4 years younger than high-Confidence animals, we are unaware of any age-related differences between 10 and 12 year old adult male rhesus monkeys in responsiveness to potential stressors; moreover, correlations between age and cortisol concentrations at each time point in the present study were all nonsignificant (all p > 0:25) suggesting that our results were not an aspect of a more general agerelated difference. Thus, we feel confident that our data reflect basal values, although we recognize that the present work requires extension to distinguish firmly between the two explanations for the low- vs. high-Confidence animals. Consequently, we offer as provisional our interpretation that the results for low-Confidence animals represent a flattened diurnal rhythm, and not a mild stress-induced response. While we are aware of no human research relating personality to variations in cortisol rhythmicity, one study that employed a healthy community sample (n ¼ 120) demonstrated that 51% had the normal ‘‘negative’’ cycle on two consecutive days, 31% had inconsistent cycles from one day to the next, and 17% of subjects had no discernable circadian rhythm (Smyth et al., 1997; see also Stone et al., 2001 for further, similar, results). Cycle type was not related to any demographic or psychological variable (including experience of stressors) measured. Unfortunately, subjects’ personality characteristics were not assessed in these studies. Health consequences have been related to aspects of cortisol rhythmicity, however, with flatter rhythms associated with earlier mortality and suppressed natural killer cell function in patients with metastatic breast cancer (Sephton et al., 2000), but also with fewer upper respiratory infection symptoms (Smyth et al., 1997; Edwards et al., 2003). Interestingly, Edwards et al. (2003) demonstrated that individuals with a ‘‘flat’’ cortisol profile spent significantly fewer hours in busy places in close proximity to others (e.g., restaurants, pubs, lectures, meetings) compared to individuals with a normal profile. This suggests that humans with a flat profile might be less socially assertive, as are our low-Confidence monkeys, who also show a flat profile. Three other studies with nonhuman primates have examined plasma cortisol concentrations and
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personality characteristics using the multidimensional rating methodology. In an earlier study (Capitanio et al., 1999), conducted with a separate cohort of animals, we found positive correlations between Confidence and Excitability and a negative correlation with Sociability for basal concentrations of cortisol taken at 15:00 h. The animals in this study, however, were experiencing on a daily basis unfamiliar and presumably stressful social manipulations that, in fact, altered HPA regulation (Capitanio et al., 1998). A study by Laudenslager et al. (1999) of juvenile rhesus monkeys on an island colony found no relationships between cortisol concentrations and their three personality factors of Insecurity, Irritability, and Sociability. Although there were some methodological differences with derivation of the personality factors, morning blood samples on these animals were collected after netting/hand capture followed by ketamine immobilization. In fact, the authors acknowledge that their cortisol concentrations represent stressed values, which is borne out by examination of their Fig. 2. Finally, Byrne and Suomi (2002) correlated cortisol concentrations with individually rated traits (i.e., the component traits that were factor-analyzed in the present study and by Laudenslager et al. (1999)). Several relationships were found with stress concentrations, but only ‘‘Strong’’ and ‘‘Submissive’’ showed correlations (positive and negative, respectively) with basal levels. It was not clear when the samples were taken in this study, but the negative relationship between basal cortisol and ‘‘Submissive’’ mirrors our result for Excitability (which includes an identically defined trait ‘‘Subordinate’’) and afternoon basal samples. In conclusion, our data suggest that cortisol concentrations in our adult male rhesus monkeys are related to personality characteristics in both expected and unexpected ways. While we recognize that our results require replication with larger samples, these data do show some intriguing consistencies with the human data. In general, however, there has been relatively little study of neuroendocrine relationships and personality factors in normal populations of either human or nonhuman primates. Even in welldesigned studies, individual variation exists in measures such as cortisol concentration; our data and the data from the few human studies described above indicate that such variation can be explained to some extent by consideration of personality characteristics. The data also suggest that greater attention should be paid to the dynamic characteristics of the HPA axis, in particular to diurnal rhythmicity. In any system, there
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are multiple characteristics such as set-points, peak values, quality and quantity of response to challenge, rates of decline, and so forth that describe the functioning of that system. It remains to be determined which factors (e.g., personality, experiences, genetics) explain individual variation in these parameters, and how such relationships affect meaningful organismic outcomes such as indices of mental or physical health. Parallel studies in both human and nonhuman animals can be a valuable strategy to address these questions.
Acknowledgements The authors thank C. Brennan for assistance in figure preparation, and L. Martson, G. Vicino, and the veterinary and animal care staff of CNPRC for technical assistance with data collection and care of the animals. Supported by MH49033 and RR00169. The California National Primate Research Center is accredited by the Association for the Assessment and Accreditation of Laboratory Animal Care International. All procedures were carried out in accordance with guidelines of the Public Health Service, USA.
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